SitesBLAST

SitesBLAST – Find functional sites

SitesBLAST

Comparing WP_015798940.1 NCBI__GCF_000023265.1:WP_015798940.1 to proteins with known functional sites using BLASTp with E ≤ 0.001.

Or try Sites on a Tree, PaperBLAST, Conserved Domains, or compare to all protein structures

Found 20 (the maximum) hits to proteins with known functional sites (download)

Q9JZG1 2-isopropylmalate synthase; Alpha-IPM synthase; Alpha-isopropylmalate synthase; EC 2.3.3.13 from Neisseria meningitidis serogroup B (strain MC58) (see 2 papers)
26% identity, 96% coverage: 9:516/530 of query aligns to 7:499/517 of Q9JZG1

query
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Q9JZG1

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D16 (= D18) binding Mn(2+)
H204 (= H211) binding Mn(2+)
H206 (= H213) binding Mn(2+)
N240 (= N247) binding Mn(2+)

Sites not aligning to the query:

366:517 Required for the condensation reaction. Not required to bind substrate

6e1jA Crystal structure of methylthioalkylmalate synthase (bjumam1.1) from brassica juncea (see paper)
29% identity, 68% coverage: 9:370/530 of query aligns to 18:391/409 of 6e1jA

query
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6e1jA

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binding coenzyme a: Q30 (= Q21), F60 (≠ W51), S63 (≠ A54), I95 (≠ F79), R97 (≠ S81), F121 (≠ V109), K132 (≠ A120), L133 (= L121), S322 (≠ A305), G323 (= G306), I324 (≠ L307), D327 (≠ S310), K331 (≠ R314), L359 (≠ M338), R362 (= R341), H363 (≠ Q342)
binding 4-(methylsulfanyl)-2-oxobutanoic acid: P192 (≠ C182), T194 (= T184), H225 (= H211), H227 (= H213)
binding manganese (ii) ion: D27 (= D18), V82 (≠ R66), E84 (= E68), H225 (= H211), H227 (= H213)

Q9FG67 Methylthioalkylmalate synthase 1, chloroplastic; 2-isopropylmalate synthase 3; EC 2.3.3.17 from Arabidopsis thaliana (Mouse-ear cress) (see paper)
29% identity, 70% coverage: 9:381/530 of query aligns to 85:469/506 of Q9FG67

query
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Q9FG67

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I

R

N

S

G

V

V

R

Y

T

T

I

-

P

K

P

I

E

D

N

T

L

R

E

Q

L

I

L

M

T

A

T

T

V

-

S

S

R

K

H

M

I

V

A

Q

E

E

L

Y

T

T

N

G

Q

L

P

Y

L

V

P

Q

P

A

Q

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S

K

P

P

Y

I

V

V

G

G

A

A

S

N

A

C

F

F

T

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E

A

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G

G

L

I

H

H

V

Q

S

D

A

G

I

I

A

L

R

K

R

N

R

R

D

S

A

T

Y

Y

E

E

H

I

I

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P

T

E

L

D

V

I

G

G

-

I

-

V

-

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-

S

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G

F

L

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V

V

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S

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I

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A

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L

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G

I

Y

D

E

L

L

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D

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D

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E

A

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L

F

R

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D

S102 (= S26) mutation to F: In gsm1-1; loss of conversion of C3 to C4 glucosinolates.
A290 (≠ G209) mutation to T: In gsm1-2; loss of conversion of C3 to C4 glucosinolates.

6ktqA Crystal structure of catalytic domain of homocitrate synthase from sulfolobus acidocaldarius (sahcs(dram)) in complex with alpha- ketoglutarate/zn2+/coa (see paper)
29% identity, 68% coverage: 8:368/530 of query aligns to 21:370/399 of 6ktqA

query
sites
6ktqA

E

K

V

V

E

G

I

I

Y

L

D

D

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x
E

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E

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D

D

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A

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L

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A

D

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E

G

A

G

G

W

H

P

P

G

A

A
x
V

N

S

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P

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D

D

-

A

-

F

I

F

Y

A

E

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A

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D

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E

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L

I

A

K

L

L

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K

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A

K

F

-

G

S

S

E

T

I

R

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A

A

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T
x
R

T
x
A

A

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E

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S

R

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D

P

I

N

E

L

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A

G

A

A

L

E

T

I

N

E

A

A

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A

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x
F

A

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A

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H

H

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L

I

K

H

A

A

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x
H

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T

L

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P

D

E

E

A

A

V

L

A

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T

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V

R

S

W

Y

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H

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M
x
R

L

F

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x
T

A

A

E
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E

H

-

F

-

D

D

G

A

W

T

R

R

H

A

D

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A

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E

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G

A

A

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D

R

R

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x
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|
T

N

V

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G

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T

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I

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F

A

P

-

D

T

I

P

E

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D

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|
H

F

A

H
|
H

N

N

D

D

S

L

G

G

C

M

A

A

V

V

A

A

N

N

S

V

L

L

L

A

A

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A

A

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G

G

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A

I

T

Q

I

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I

Q

H

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L

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N

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Y

L

G

G

E

E

R

R

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G

G

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I

A

A

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P

L

L

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Q

P

V

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V

I

A

A

A

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A

L

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L

Y

K

H

R

F

S

G

V

I

R

E

T

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I

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-

E

-

N

D

L

L

E

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L

K

L

L

T

S

T

E

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S

A

R

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L

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A

E

E

K

L

Y

T

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P

Q

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S

F

P

P

Y

I

V

T

G

G

A

D

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Y

A

A

F

F

T

V

H

H

K

K

A

A

G

G

L

V

H

H

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A

A

G

I

V

A

L

R

N

R

D

R

P

D

K

A

T

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Y

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E

H

F

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D

P

P

P

T

E

L

T

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F

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T

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F

Y

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S

A

I

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G

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V

L

L

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A

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L

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K

binding 2-oxoglutaric acid: R30 (= R17), R154 (≠ M147), T156 (≠ D149), E158 (= E151), S184 (≠ V180), T188 (= T184), H216 (= H211), H218 (= H213)
binding coenzyme a: V67 (≠ A54), R96 (≠ T87), A97 (≠ T88), F116 (≠ V109), H128 (≠ L121), E158 (= E151)
binding zinc ion: E31 (≠ D18), H216 (= H211), H218 (= H213)

Q9FN52 Methylthioalkylmalate synthase 3, chloroplastic; 2-isopropylmalate synthase 2; Methylthioalkylmalate synthase-like; EC 2.3.3.17 from Arabidopsis thaliana (Mouse-ear cress) (see paper)
27% identity, 68% coverage: 9:370/530 of query aligns to 85:458/503 of Q9FN52

query
sites
Q9FN52

V

V

E

R

I

V

Y

L

D

D

T

T

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L

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E

-

F

-

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-

A

-

I

-

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T

-

I

A

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N

A

E

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D

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A

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A

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I

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A

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T

C

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A

R

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D

T

I

T

E

A

A

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-

S

-

D

-

P

-

N

T

L

W

A

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A

A

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P

E

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A

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-

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-

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-

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D

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A

A

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G

A

A

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C

A

D

D

T

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G
|
G

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D

E

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F

G

G

P

E

I

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A

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D

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D

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A

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A

D

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I

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V

L

F

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A

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I

H

H

F

C

H

H

N

N

D

D

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C

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A

A

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T

A

A

N

N

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T

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I

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A

G

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I

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C

H

A

G

G

V

A

I

R

Q

Q

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E

G

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C

T

M

I

N

N

G

G

Y

I

G

G

E

E

R

R

T

S

G

G

N

N

A

A

N

P

L

L

V

E

P

E

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I

V

A

M

G

A

L

L

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-

C

-

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-

G

-

E

S

S

L

L

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M

R

D

S

G

V

V

R

Y

T

T

I

-

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K

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N

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L

I

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M

T

A

T

T

V

-

S

S

R

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H

M

I

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A

Q

E

E

L

H

T

T

N

G

Q

M

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Q

P

P

Q

H

S

K

P

P

Y

I

V

V

G

G

A

D

S

N

A

C

F

F

T

V

H

H

K

E

A

S

G

G

L

I

H

H

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Q

S

D

A

G

I

I

A

L

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K

R

N

R

R

D

S

A

T

Y

Y

E

E

H

I

I

L

D

S

P

P

T

E

L

D

V

V

G

G

-

I

-

V

-

K

-

S

N

E

T

N

T

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R

G

F

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M

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A

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G

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A

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E

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D

D

E

D

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I

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A

N

E

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R

L

Y

K

R

D

E

L

L

G263 (= G186) mutation to E: In gsm2-1; loss of activity and lack of C6, C7 and C8 aliphatic glucosinolates.

O87198 Homocitrate synthase; HCS; EC 2.3.3.14 from Thermus thermophilus (strain ATCC BAA-163 / DSM 7039 / HB27) (see paper)
29% identity, 69% coverage: 8:374/530 of query aligns to 3:359/376 of O87198

query
sites
O87198

E

E

V

W

E

K

I

I

Y

I

D

D

T

S

T

T

L

L

R
|
R

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x
E

G

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E

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Q

F

E

E

G

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I

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D

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A

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D

A

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L

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G

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V

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T

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P

G

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A

A

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Q

-

S

-

R

K

K

D

D

A

A

A

E

F

V

F

L

A

A

R

-

A

-

R

-

D

-

E

S

L

L

A

G

L

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H

-

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A

A

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L

V

V

V

A

T

F
x
H

G

I

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Q

T

C

R

R

R

-

A

-

S

-

T

-

A

-

E

-

S

L

D

D

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A

N

A

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A

V

A

A

L

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T

E

N

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A

G

G

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G

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A
x
D

C

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I

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A

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A

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A

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-

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A

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A

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A

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x
R

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S

A

A

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T

F

F

D

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S

W

E

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E

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D

D

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S

L

F

A

A

V

L

Y

D

E

V

A

L

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A

A

A

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A

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A

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D

D

A

-

G

-

A

-

E

-

R

R

L

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V

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C

A

D

D

T
|
T

N

V

G

G

G

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A

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Q

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V

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Y

P

A

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A

R

A

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V

V

A

G

T

P

P

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L

V

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H

E

F

F

H
|
H

-

G

-
x
H

N

N

D

D

S

T

G

G

C

C

A

A

V

I

A

A

N

N

S

A

L

Y

L

E

A

A

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I

A

E

H

A

G

G

V

A

I

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V

Q

D

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C

T

M

I

N

L

G

G

Y

I

G

G

E

E

R

R

T

N

G

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N

I

A

T

N

P

L

L

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P

G

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I

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A

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R

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M

S

Y

L

-

K

-

R

-

S

-

V

-

R

-

T

T

I

L

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Q

P

P

E

E

-

Y

-

V

-

R

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-

Y

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L

L

E

E

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M

L

L

T

P

T

E

V

L

S

D

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A

A

E

R

L

M

T

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N

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F

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N

P

Y

Y

I

V

T

G

G

A

E

S

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A

A

F

F

T

S

H

H

K

K

A

A

G

G

L

M

H

H

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A

A

I

I

A

Y

R

I

R

N

R

P

D

E

A

A

Y

Y

E

E

H

P

I

Y

D

P

P

P

T

E

L

V

V

F

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N

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T

R

R

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F

L

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I

-

A

S

S

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M

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G

G

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H

S

A

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I

Q

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L

A

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A

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E

L

L

G

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I

L

D

H

L

Y

G

G

E

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D

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A

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V

L

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Q

R

H

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K

D

A

L

L

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D

R

R

G

G

R12 (= R17) binding 2-oxoglutarate
E13 (≠ D18) binding Mg(2+)
H72 (≠ F79) binding 2-oxoglutarate; mutation to L: Significant decrease in sensitivity to lysine inhibition. Large decrease in affinity for 2-oxoglutarate. Almost no effect on affinity for acetyl-CoA and on turnover number.
D92 (≠ A106) binding L-lysine
R133 (≠ M147) binding 2-oxoglutarate
S135 (≠ D149) binding L-lysine
T166 (= T184) binding 2-oxoglutarate; binding L-lysine
H195 (= H213) binding Mg(2+)
H197 (vs. gap) binding Mg(2+)

4ov9A Structure of isopropylmalate synthase binding with alpha- isopropylmalate (see paper)
27% identity, 72% coverage: 6:384/530 of query aligns to 1:376/380 of 4ov9A

query
sites
4ov9A

P

P

A

K

E

T

V

I

E

H

I

I

Y

Q

D

D

T

V

T

T

L

L

R
|
R

D
|
D

G

G

S

N

Q
|
Q

Q

A

E

L

G

K

I

R

S

P

L

W

S

T

V

I

D

D

D

E

K

K

L

I

K

E

V

V

A

F

R

D

Q

L

L

L

D

V

A

E

L

L

G

N

V

V

H

D

Y

G

I

I

E

E

G

V

G

G

W

F

P

P

G

S

A

S

N

N

P

-

K

-

D

-

A

-

F

-

A

-

R

-

A

-

R

-

D

-

E

E

L

T

A

E

L

F

H

H

T

T

A

C

Q

Q

L

V

V

L

A

S

F

K

G

R

S

A

T

P

R

K

R

G

A

K

S

P

T

I

T

A

A

A

E
x
L

S

S

D

R

P

A

N

N

L

Q

-

N

-

E

-

I

-

A

-

V

-

T

-

W

A

E

A

A

L

I

T

Q

N

K

A

A

G

D

V

C

G

P

L

R

A

M

C

H

I

I

V

V

A

Y

K

P

A

V

W

S

D

D

V

F

H

S

V

I

I

K

H

H

A

V

L

L

R

K

T

I

S

S

L

E

P

K

E

E

A

V

V

L

A

Q

M

K

V

I

A

R

D

N

S

S

V

I

-

S

-

F

-

A

R

R

W

S

L

I

V

V

D

G

H

P

G

G

I

I

R

E

V

I

M

Q

L

F

D

S

A

G

E

E

H

H

F

F

F

G

D

D

G

A

W

I

R

E

H

-

D

N

R

F

S

A

F

F

A

T

L

K

D

E

V

A

L

F

A

L

A

T

A

A

A

I

D

E

A

A

G

G

A

A

E

N

R

I

L

I

V

N

L

L

C

P

D

N

T
|
T

N

V

G

E

G

R

T

Y

L

R

P

P

D

M

D

V

V

F

G

V

P

N

I

M

V

V

D

K

D

E

V

I

R

K

A

D

A

V

V

V

A

K

T

D

P

K

-

A

-

I

L

I

G

S

V

I

H
|
H

F

T

H
|
H

N

N

D

D

S

L

G

G

C

M

A

A

V

T

A

A

N

T

S

S

L

V

L

E

A

S

V

V

A

Y

H

V

G

G

V

A

I

E

Q

Q

V

I

Q

E

G

V

C

A

M

L

N

N

G

G

Y

L

G

G

E

E

R

R

T

A

G

G

N

N

A

T

N

N

L

L

V

Y

P

E

V

T

I

A

A

I

G

A

L

L

S

H

L

Q

K

N

R

G

S

E

V

N

R

L

T

N

I

I

P

-

E

-

N

N

L

F

E

Q

L

R

L

I

T

Y

T

P

V

T

S

A

R

K

H

R

I

I

A

S

E

E

L

L

T

T

N

G

Q

I

P

P

L

I

P

G

P

E

Q

K

S

T

P

P

Y

I

V

I

G

G

A

E

S

D

A

I

F

F

T

S

H

H

K

R

A

S

G

G

L

I

H

H

V

-

S

Q

A

T

I

L

A

H

R

Q

R

S

R

K

D

G

A

A

Y

Y

E

R

H

T

I

F

D

S

P

P

T

E

L

F

V

V

G

G

N

R

T

M

T

D

R

K

F

E

V

T

V

I

S

S

-

F

-

T

E

N

M

Q

A

S

G

G

R

H

Q

K

S

A

I

I

Q

E

L

F

K

L

A

L

T

H

Q

Q

L

R

G

G

I

I

D

Q

L

V

G

S

E

K

D

E

D

G

I

I

A

H

E

H

V

L

L

F

R

S

R

L

L

A

K

K

D

S

L

I

E

S

H

S

R

R

G

E

Y

N

H

N

F

R

E

E

A

I

A

T

D

E

G

A

S

E

L

L

active site: Q16 (= Q21)
binding (2S)-2-hydroxy-2-(propan-2-yl)butanedioic acid: R12 (= R17), L73 (≠ E90), T176 (= T184), H205 (= H211), H207 (= H213)
binding zinc ion: D13 (= D18), H205 (= H211), H207 (= H213)

4ov4A Isopropylmalate synthase binding with ketoisovalerate (see paper)
27% identity, 72% coverage: 6:384/530 of query aligns to 1:374/379 of 4ov4A

query
sites
4ov4A

P

P

A

K

E

T

V

I

E

H

I

I

Y

Q

D

D

T

V

T

T

L

L

R
|
R

D
|
D

G

G

S

N

Q
|
Q

Q

A

E

L

G

K

I

R

S

P

L

W

S

T

V

I

D

D

D

E

K

K

L

I

K

E

V

V

A

F

R

D

Q

L

L

L

D

V

A

E

L

L

G

N

V

V

H

D

Y

G

I

I

E

E

G

V

G

G

W

F

P

P

G

S

A

S

N

N

P

-

K

-

D

-

A

-

F

-

A

-

R

-

A

-

R

-

D

-

E

E

L

T

A

E

L

F

H

H

T

T

A

C

Q

Q

L

V

V

L

A

S

F

K

G

R

S

A

T

P

R

K

R

G

A

K

S

P

T

I

T

A

A

A

E

L

S

S

D

R

P

A

N

N

L

Q

-

N

-

E

-

I

-

A

-

V

-

T

-

W

A

E

A

A

L

I

T

Q

N

K

A

A

G

D

V

C

G

P

L

R

A

M

C

H

I

I

V

V

A

Y

K

P

A

V

W

S

D

D

V

F

H

S

V

I

I

K

H

H

A

V

L

L

R

K

T

I

S

S

L

E

P

K

E

E

A

V

V

L

A

Q

M

K

V

I

A

R

D

N

S

S

V

I

-

S

-

F

-

A

R

R

W

S

L

I

V

V

D

G

H

P

G

G

I

I

R

E

V

I

M

Q

L

F

D

S

A

G

E

E

H

H

F

F

F

G

D

D

G

A

W

I

R

E

H

-

D

N

R

F

S

A

F

F

A

T

L

K

D

E

V

A

L

F

A

L

A

T

A

A

A

I

D

E

A

A

G

G

A

A

E

N

R

I

L

I

V

N

L

L

C
x
P

D

N

T
|
T

N

V

G

E

G

R

T

Y

L

R

P

P

D

M

D

V

V

F

G

V

P

N

I

M

V

V

D

K

D

E

V

I

R

K

A

D

A

V

V

V

A

K

T

D

P

K

-

A

-

I

L

I

G

S

V

I

H
|
H

F

T

H
|
H

N

N

D

D

S

L

G

G

C

M

A

A

V

T

A

A

N

T

S

S

L

V

L

E

A

S

V

V

A

Y

H

V

G

G

V

A

I

E

Q

Q

V

I

Q

E

G

V

C

A

M

L

N

N

G

G

Y

L

G

G

E

E

R

R

T

A

G

G

N

N

A

T

N

N

L

L

V

Y

P

E

V

T

I

A

A

I

G

A

L

L

S

H

L

Q

K

N

R

G

S

E

V

N

R

L

T

N

I

I

P

-

E

-

N

N

L

F

E

Q

L

R

L

I

T

Y

T

P

V

T

S

A

R

K

H

R

I

I

A

S

E

E

L

L

T

T

N

G

Q

I

P

P

L

I

P

G

P

E

Q

K

S

T

P

P

Y

I

V

I

G

G

A

E

S

D

A

I

F

F

T

S

H

H

K

R

A

S

G

G

L

I

H

H

V

Q

S

H

A

-

I

-

A

-

R

Q

R

S

R

K

D

G

A

A

Y

Y

E

R

H

T

I

F

D

S

P

P

T

E

L

F

V

V

G

G

N

R

T

M

T

D

R

K

F

E

V

T

V

I

S

S

-

F

-

T

E

N

M

Q

A

S

G

G

R

H

Q

K

S

A

I

I

Q

E

L

F

K

L

A

L

T

H

Q

Q

L

R

G

G

I

I

D

Q

L

V

G

S

E

K

D

E

D

G

I

I

A

H

E

H

V

L

L

F

R

S

R

L

L

A

K

K

D

S

L

I

E

S

H

S

R

R

G

E

Y

N

H

N

F

R

E

E

A

I

A

T

D

E

G

A

S

E

L

L

active site: Q16 (= Q21)
binding 3-methyl-2-oxobutanoic acid: R12 (= R17), P174 (≠ C182), T176 (= T184), H205 (= H211), H207 (= H213)
binding zinc ion: D13 (= D18), H205 (= H211), H207 (= H213)

2zyfA Crystal structure of homocitrate synthase from thermus thermophilus complexed with magnesuim ion and alpha-ketoglutarate (see paper)
30% identity, 62% coverage: 8:336/530 of query aligns to 3:314/314 of 2zyfA

query
sites
2zyfA

E

E

V

W

E

K

I

I

Y

I

D

D

T

S

T

T

L

L

R
|
R

D
x
E

G

G

S

E

Q
|
Q

Q

F

E

E

G

K

I

A

S

N

L

F

S

S

V

T

D

Q

D

D

K

K

L

V

K

E

V

I

A

A

R

K

Q

A

L

L

D

D

A

E

L

F

G

G

V

I

H

E

Y

Y

I

I

E

E

G

V

G

T

W

T

P

P

G

V

A

A

N

S

P

P

-

Q

-

S

-

R

K

K

D

D

A

A

A

E

F

V

F

L

A

A

R

S

A

L

R

G

D

L

E

K

L

A

A

K

L

V

H

V

T

T

A
x
H

Q

I

L

Q

V

C

A

R

F

L

G

D

S

A

T

A

R

K

R

V

A

A

S

V

T

E

T

T

A

G

E

V

S

Q

D

G

P

I

N

D

L

L

A
x
L

A

F

L

G

T

T

N

S

A

K

G

G

V

R

G

D

L

I

A

P

C

R

I

I

V

I

A

E

K

E

A

A

W

K

D

E

V

-

H

-

V

V

I

I

H

A

A

Y

L

I

R

R

T

E

S

A

L

A

P

P

E

H

A

-

V

-

A

-

M

-

V

-

A

-

D

-

S

-

V

-

R

-

W

-

L

-

V

-

D

-

H

-

G

-

I

V

R

E

V

V

M
x
R

L

F

D

S

A

A

E

E

H

D

F

T

F

F

D

R

G

S

W

E

R

E

H

Q

D

D

R

L

S

L

F

A

A

V

L

Y

D

E

V

A

L

V

A

A

A

P

A

Y

A

V

D

D

A

-

G

-

A

-

E

-

R

R

L

V

V

G

L

L

C

A

D

D

T
|
T

N

V

G

G

G

V

T

A

L

T

P

P

D

R

D

Q

V

V

G

Y

P

A

I

L

V

V

D

R

D

E

V

V

R

R

A

R

A

V

V

V

A

G

T

P

P

R

L

V

G

D

V

I

H

E

F

F

-
x
H

-

G

H
|
H

N

N

D

D

S

T

G

G

C

C

A

A

V

I

A

A

N

N

S

A

L

Y

L

E

A

A

V

I

A

E

H

A

G

G

V

A

I

T

Q

H

V

V

Q

D

G

T

C

T

M

I

N

L

G

G

Y

I

G

G

E

E

R

R

T

N

G

G

N

I

A

T

N

P

L

L

V

-

P

-

V

-

I

-

A

-

G

G

L

G

S

F

L

L

K

A

R

R

S

-

V

M

R

Y

T

T

I

L

P

Q

P

P

E

E

-

Y

-

V

-

R

-

K

-

Y

N

K

L

L

E

E

L

M

L

L

T

P

T

E

V

L

S

D

R

R

H

M

I

V

A

A

E

R

L

M

T

V

N

G

Q

V

P

E

L

I

P

P

P

F

Q

N

S

N

P

Y

Y

I

V

T

G

G

A

E

S

T

A

A

F

F

T

S

H

H

K

K

A

A

G

G

L

M

H

H

V

L

S

K

A

A

I

I

A

Y

R

I

R

N

R

P

D

E

A

A

Y

Y

E

E

H

P

I

Y

D

P

P

P

T

E

L

V

V

F

G

G

N

V

T

K

T

R

R

K

F

L

V

I

S

A

active site: Q16 (= Q21)
binding 2-oxoglutaric acid: R12 (= R17), H72 (≠ A74), L94 (≠ A96), R127 (≠ M147), T160 (= T184), H189 (vs. gap)
binding magnesium ion: E13 (≠ D18), H189 (vs. gap), H191 (= H213)

3a9iA Crystal structure of homocitrate synthase from thermus thermophilus complexed with lys (see paper)
28% identity, 69% coverage: 8:374/530 of query aligns to 2:330/347 of 3a9iA

query
sites
3a9iA

E

E

V

W

E

K

I

I

Y

I

D

D

T

S

T

T

L

L

R
|
R

D
x
E

G

G

S

E

Q

Q

Q

F

E

E

G

K

I

A

S

N

L

F

S

S

V

T

D

Q

D

D

K

K

L

V

K

E

V

I

A

A

R

K

Q

A

L

L

D

D

A

E

L

F

G

G

V

I

H

E

Y

Y

I

I

E

E

G

V

G

T

W

T

P

P

G

V

A

A

N

S

P

P

-

Q

-

S

-

R

K

K

D

D

A

A

A

E

F

V

F

L

A

A

R

S

A

L

R

G

D

L

E

K

L

A

A

K

L

V

H

V

T

T

A

H

Q

I

L

Q

V

C

A

R

F

L

G

D

S

A

T

A

R

K

R

V

A

A

S

V

T

E

T

T

A

G

E

V

S

Q

D

G

P

I

N
x
D

L

L

A

L

A

F

L

G

T

T

N

S

A

K

G

Y

V

L

G

D

L

I

A

P

C

R

I

I

V

I

A

E

K

E

A

A

W

K

D

E

V

-

H

-

V

V

I

I

H

A

A

Y

L

I

R

R

T

E

S

A

L

A

P

P

E

H

A

-

V

-

A

-

M

-

V

-

A

-

D

-

S

-

V

-

R

-

W

-

L

-

V

-

D

-

H

-

G

-

I

V

R

E

V

V

M

R

L

F

D
x
S

A

A

E

E

H

D

F

T

F

F

D

R

G

S

W

E

R

E

H

Q

D

D

R

L

S

L

F

A

A

V

L

Y

D

E

V

A

L

V

A

A

A

P

A

Y

A

V

D

D

A

-

G

-

A

-

E

-

R

R

L

V

V

G

L

L

C

A

D

D

T
|
T

N

V

G

G

G

V

T

A

L

T

P

P

D

R

D

Q

V

V

G

Y

P

A

I

L

V

V

D

R

D

E

V

V

R

R

A

R

A

V

V

V

A

G

T

P

P

R

L

V

G

D

V

I

H

E

F

F

-
x
H

-

G

H
|
H

N

N

D

D

S

T

G

G

C

C

A

A

V

I

A

A

N

N

S

A

L

Y

L

E

A

A

V

I

A

E

H

A

G

G

V

A

I

T

Q

H

V

V

Q

D

G

T

C

T

M

I

N

L

G

G

Y

I

G

G

E

E

R

R

T

N

G

G

N

I

A

T

N

P

L

L

V

G

P

G

V

F

I

L

A

A

G

R

L

M

S

Y

L

-

K

-

R

-

S

-

V

-

R

-

T

T

I

L

P

Q

P

P

E

E

-

Y

-

V

-

R

-

K

-

Y

N

K

L

L

E

E

L

M

L

L

T

P

T

E

V

L

S

D

R

R

H

M

I

V

A

A

E

R

L

M

T

V

N

G

Q

V

P

E

L

I

P

P

P

F

Q

N

S

N

P

Y

Y

I

V

T

G

G

A

E

S

T

A

A

F

F

T

S

H

H

K

K

A

A

G

G

L

M

H

H

V

L

S

K

A

A

I

I

A

Y

R

I

R

N

R

P

D

E

A

A

Y

Y

E

E

H

P

I

Y

D

P

P

P

T

E

L

V

V

F

G

G

N

V

T

K

T

-

R

-

F

-

V

-

S

-

E

-

M

-

A

-

G

-

R

-

Q

-

S

-

I

-

Q

-

L

-

K

-

A

-

T

-

Q

-

L

-

G

G

I

L

D

H

L

Y

G

G

E

E

D

E

I

L

A

H

E

R

V

V

L

T

R

Q

R

H

L

I

K

K

D

A

L

L

E

A

H

D

R

R

G

G

binding cobalt (ii) ion: E12 (≠ D18), H188 (vs. gap), H190 (= H213)
binding lysine: R11 (= R17), D91 (≠ N94), S128 (≠ D149), T159 (= T184), H188 (vs. gap), H190 (= H213)

2ztjA Crystal structure of homocitrate synthase from thermus thermophilus complexed with alpha-ketoglutarate (see paper)
30% identity, 62% coverage: 8:336/530 of query aligns to 3:312/312 of 2ztjA

query
sites
2ztjA

E

E

V

W

E

K

I

I

Y

I

D

D

T

S

T

T

L

L

R
|
R

D
x
E

G

G

S

E

Q
|
Q

Q

F

E

E

G

K

I

A

S

N

L

F

S

S

V

T

D

Q

D

D

K

K

L

V

K

E

V

I

A

A

R

K

Q

A

L

L

D

D

A

E

L

F

G

G

V

I

H

E

Y

Y

I

I

E

E

G

V

G

T

W

T

P

P

G

V

A

A

N

S

P

P

-

Q

-

S

-

R

K

K

D

D

A

A

A

E

F

V

F

L

A

A

R

S

A

L

R

G

D

L

E

K

L

A

A

K

L

V

H

V

T

T

A
x
H

Q

I

L

Q

V

C

A

R

F

L

G

D

S

A

T

A

R

K

R

V

A

A

S

V

T

E

T

T

A

G

E

V

S

Q

D

G

P

I

N

D

L

L

A

-

L
|
L

T

F

N

G

A

T

G

G

V

R

G

D

L

I

A

P

C

R

I

I

V

I

A

E

K

E

A

A

W

K

D

E

V

-

H

-

V

V

I

I

H

A

A

Y

L

I

R

R

T

E

S

A

L

A

P

P

E

H

A

-

V

-

A

-

M

-

V

-

A

-

D

-

S

-

V

-

R

-

W

-

L

-

V

-

D

-

H

-

G

-

I

V

R

E

V

V

M
x
R

L

F

D

S

A

A

E

E

H

D

F

T

F

F

D

R

G

S

W

E

R

E

H

Q

D

D

R

L

S

L

F

A

A

V

L

Y

D

E

V

A

L

V

A

A

A

P

A

Y

A

V

D

D

A

-

G

-

A

-

E

-

R

R

L

V

V

G

L

L

C
x
A

D

D

T
|
T

N

V

G

G

G

V

T

A

L

T

P

P

D

R

D

Q

V

V

G

Y

P

A

I

L

V

V

D

R

D

E

V

V

R

R

A

R

A

V

V

V

A

G

T

P

P

R

L

V

G

D

V

I

H

E

F

F

-
x
H

-

G

H
|
H

N

N

D

D

S

T

G

G

C

C

A

A

V

I

A

A

N

N

S

A

L

Y

L

E

A

A

V

I

A

E

H

A

G

G

V

A

I

T

Q

H

V

V

Q

D

G

T

C

T

M

I

N

L

G

G

Y

I

G

G

E

E

R

R

T

N

G

G

N

I

A

T

N

P

L

L

V

-

P

-

V

-

I

-

A

-

G

G

L

G

S

F

L

L

K

A

R

R

S

-

V

M

R

Y

T

T

I

L

P

Q

P

P

E

E

-

Y

-

V

-

R

-

K

-

Y

N

K

L

L

E

E

L

M

L

L

T

P

T

E

V

L

S

D

R

R

H

M

I

V

A

A

E

R

L

M

T

V

N

G

Q

V

P

E

L

I

P

P

P

F

Q

N

S

N

P

Y

Y

I

V

T

G

G

A

E

S

T

A

A

F

F

T

S

H

H

K

K

A

A

G

G

L

M

H

H

V

L

S

K

A

A

I

I

A

Y

R

I

R

N

R

P

D

E

A

A

Y

Y

E

E

H

P

I

Y

D

P

P

P

T

E

L

V

V

F

G

G

N

V

T

K

T

R

R

K

F

L

V

I

S

A

active site: Q16 (= Q21)
binding 2-oxoglutaric acid: R12 (= R17), H72 (≠ A74), L94 (= L98), R125 (≠ M147), A156 (≠ C182), T158 (= T184), H187 (vs. gap), H189 (= H213)
binding copper (ii) ion: E13 (≠ D18), H187 (vs. gap), H189 (= H213)

Q8F3Q1 (R)-citramalate synthase CimA; LiCMS; EC 2.3.3.21 from Leptospira interrogans serogroup Icterohaemorrhagiae serovar Lai (strain 56601) (see 2 papers)
26% identity, 93% coverage: 9:500/530 of query aligns to 8:491/516 of Q8F3Q1

query
sites
Q8F3Q1

V

L

E

E

I

I

Y

L

D

D

T

V

T

T

L

L

R
|
R

D
|
D

G

G

S

E

Q

Q

Q

T

E

R

G

G

I

V

S

S

L

F

S

S

V

T

D

S

D

E

K

K

L

L

K

N

V

I

A

A

R

K

-

F

Q

L

L

L

D

Q

A

K

L

L

G

N

V

V

H

D

Y

R

I

V

E

E

G

I

G

A

W

S

P

A

G

R

A

V

N

S

P

K

K

G

D

E

A

L

A

E

F

T

F

V

A

Q

R

K

A

I

R

M

D

E

E

W

L

A

A

A

L

-

H

-

T

T

A

E

Q

Q

L

L

V

-

A

-

F

-

G

-

S

-

T

T

R

E

R

R

A

I

S

E

T

I

T
x
L

A

G

E
x
F

S

V

D

D

P

G

N

N

L

K

A

T

A

V

-

D

-

W

L

I

T

K

N

D

A

S

G

G

V

A

G

K

L

V

A

L

C

N

I

L

V
x
L

A

T

K

K

A

G

W

S

D

L

V

H

H

H

V

L

I

E

H

K

A

Q

L

L

R

G

T

K

S

T

L

P

P

K

E

E

A

F

V

F

A

T

M

D

V

V

A

S

D

F

S

V

V

I

R

E

W

Y

L

A

V

I

D

K

H

S

G

G

I

L

R

K

V

I

M

N

L

V

D
x
Y

A

L

E
|
E

H

D

F

W

F

S

D

N

G

G

W

F

R

R

H

N

D

S

R

P

S

D

F

Y

A

V

L

K

D

S

V

L

L

V

A

E

A

H

A

L

A

S

D

K

A

E

G

H

A

I

E

E

R

R

L

I

V

F

L

L

C

P

D

D

T
|
T

N

L

G

G

G

V

T

L

L

S

P

P

D

E

V

T

G

F

P

Q

I

G

V

V

D

D

D

S

-

L

V

I

R

Q

A

K

A

Y

V

P

A

D

T

I

P

H

L

F

G

E

V

F

H

H

F

G

H

H

N

N

D

D

S

Y

G

D

C

L

A

S

V

V

A

A

N

N

S

S

L

L

L

Q

A

A

V

I

A

R

H

A

G

G

V

V

I

K

Q

G

V

L

Q

H

G

A

C

S

M

I

N

N

G

G

Y

L

G

G

E

E

R

R

T

A

G

G

N

N

A

T

N

P

L

L

V

E

P

A

V

L

I

V

A

T

G

T

L

I

S

H

L

D

K

K

R

S

S

N

V

S

R

K

T

T

I

-

P

-

P

N

E

I

N

N

L

E

E

I

L

A

L

I

T

T

T

E

V

A

S

S

R

R

H

L

I

V

A

E

E

V

L

F

T

S

N

G

Q

K

P

R

L

I

P

S

P

A

Q

N

S

R

P

P

Y

I

V

V

G

G

A

E

S

D

A

V

F

F

T

T

H

Q

K

T

A

A

G

G

L

V

H
|
H

V

A

S
x
D

A

G

I

D

A

K

R

K

R

G

R
x
N

D
x
L

A
x
Y

Y

A

E

N

H

P

I

I

D

L

P

P

T

E

L

R

V

F

G

G

N

R

T

K

T

R

R

S

F

Y

V

A

V

L

S

G

E

K

M

L

A

A

G

G

R

K

Q

A

S

S

I

I

Q

S

L

E

K

N

A

V

T

K

Q

Q

L

L

G

G

I

M

D

V

L

L

G

S

E

E

D

V

I

L

A

Q

E

K

V

V

L

L

R

E

R

R

L

V

K

I

D

E

L

L

E

G

H

D

R

Q

G

N

Y

K

H

L

F

V

E

T

A

P

A

E

D

D

G

-

S

-

L

L

E

P

L

F

L

I

R

A

R

D

A

V

S

S

G

G

W

R

T

T

L

G

D

E

D

K

V

V

A

L

V

-

E

-

S

-

Y

-

R

-

T

T

I

I

S

K

D

S

C

C

M

N

T

I

D

H

-

S

-

G

-

I

G

G

P

I

R

R

A

P

T

-

E

H

A

A

T

Q

V

I

K

E

L

L

T

E

V

Y

N

Q

D

G

R

K

R

I

V

H

I

K

A

E

T

I

A

S

E

E

G

G

N

D

G

G

P

G

V
x
Y

N
x
D

A

A

L

F

D

M

E

N

A

A

L

L

R

T

A

K

A

I

-

T

-

N

-

R

L

L

D

G

P

I

A

S

F

I

P

P

L

-

K

-

T

-

V

-

K

K

L
|
L

T

I

D

D

F
x
Y

K

E

V

V

R

R

V
x
I

L

P

D

P

S

G

D

G

Q

K

G

-

T
|
T

D

D

A

A

T

L

V
|
V

R

E

V

T

L

R

I

I

D

T

F

W

Q

N

-

K

-

S

-

L

-

D

-

L

D

E

P

E

E

D

D

Q

T

T

W

F

T

K

T

T

T

M

G

G

V

V

R16 (= R17) mutation R->K,Q: Loss of activity.
RD 16:17 (= RD 17:18) binding pyruvate
D17 (= D18) mutation to A: 34-fold increase in Km for pyruvate and 315-fold decrease in kcat.; mutation to N: 4.4-fold increase in Km for pyruvate and 480-fold decrease in kcat.
L81 (≠ T88) mutation to A: 4.7-fold increase in Km for pyruvate and 15.7-fold decrease in kcat.; mutation to V: 3.3-fold increase in Km for pyruvate and 10.1-fold decrease in kcat.
F83 (≠ E90) mutation to A: 5-fold increase in Km for acetyl-CoA and 120-fold decrease in kcat.
L104 (≠ V109) mutation to V: 1.8-fold increase in Km for pyruvate and 3.4-fold decrease in kcat.
Y144 (≠ D149) binding pyruvate; mutation to L: 259-fold increase in Km for pyruvate and 76-fold decrease in kcat.; mutation to V: 114-fold increase in Km for pyruvate and 5.3-fold decrease in kcat.
E146 (= E151) mutation E->D,Q: Minor effects on the binding of acetyl-CoA, but causes a strong decrease in kcat.
T179 (= T184) binding pyruvate; mutation to A: 16.4-fold increase in Km for pyruvate and 186-fold decrease in kcat.
H302 (= H308) mutation H->A,N: Loss of activity.
D304 (≠ S310) mutation to A: 5.2-fold increase in Km for acetyl-CoA and 16.6-fold decrease in kcat.
N310 (≠ R316) mutation to A: 2.2-fold increase in Km for acetyl-CoA and 1.7-fold decrease in kcat.
L311 (≠ D317) mutation to A: 8-fold increase in Km for acetyl-CoA and 6-fold decrease in kcat.
Y312 (≠ A318) mutation to A: Loss of activity.
Y430 (≠ V441) mutation to L: No change in Km for acetyl-CoA and 2.3-fold decrease in kcat. Severely impairs inhibition by isoleucine.
D431 (≠ N442) mutation to A: 1.8-fold decrease in Km for acetyl-CoA and 5-fold decrease in kcat.
L451 (= L464) mutation to V: 1.5-fold increase in Km for acetyl-CoA and 4.3 decrease in kcat.
Y454 (≠ F467) mutation to A: 1.4 decrease in Km for acetyl-CoA and 17-fold decrease in kcat. Still inhibited by isoleucine and weakly inhibited by leucine.
I458 (≠ V471) mutation to A: 1.3-fold decrease in Km for acetyl-CoA and 14-fold decrease in kcat. Abolishes inhibition by isoleucine.
T464 (= T478) mutation to A: 1.8-fold decrease in Km for acetyl-CoA and 4.3-fold decrease in kcat.
V468 (= V482) mutation to A: No change in Km for acetyl-CoA and 2-fold decrease in kcat. Increases inhibition by isoleucine and leucine becomes an effective inhibitor.

Sites not aligning to the query:

493 P→A: 1.5-fold decrease in Km for acetyl-CoA and 2.6-fold decrease in kcat.
495 Q→A: 1.6-fold decrease in Km for acetyl-CoA and 2.8-fold decrease in kcat.

3rmjB Crystal structure of truncated alpha-isopropylmalate synthase from neisseria meningitidis (see paper)
27% identity, 56% coverage: 9:304/530 of query aligns to 4:295/308 of 3rmjB

query
sites
3rmjB

V

V

E

I

I

I

Y

F

D

D

T

T

L

L

R

R

D
|
D

G

G

S

E

Q
|
Q

Q

S

E

P

G

G

I

A

S

A

L

M

S

T

V

K

D

E

K

K

L

I

K

R

V

V

A

A

R

R

Q

Q

L

L

D

E

A

K

L

L

G

G

V

V

H

D

Y

I

I

I

E

E

G

A

G

G

W

F

P

A

G

A

A

A

N

S

P

P

K

G

D

D

-

F

-

E

-

A

-

V

-

N

-

A

-

I

-

A

-

K

-

T

-

I

-

T

-

K

-

S

-

T

A

V

A

C

F

S

F

L

A

S

R

R

A

A

R

I

D

E

E

R

L

D

A

I

L

R

H

Q

T

A

A

G

Q

E

L

A

V

V

A

A

F

P

G

A

S

P

T

K

R

K

R

R

A

I

S

H

T

T

T

F

A

I

E

A

S

T

D

S

P

P

N

-

L

-

A

-

L

-

T

-

N

-

A

-

G

-

V

-

G

-

L

-

A

-

C

-

I

-

V

-

A

-

K

-

A

-

W

-

D

-

V

I

H

H

V

M

I

E

H

Y

A

K

L

L

R

K

T

M

S

K

L

P

P

K

E

Q

A

V

V

I

A

E

M

A

V

A

A

V

D

K

S

A

V

V

R

K

W

I

L

A

V

R

D

E

H

Y

G

T

I

D

R

D

V

V

M

E

L

F

D

S

A

C

E

E

H

-

F

-

D

D

G

A

W

L

R

R

H

S

D

E

R

I

S

D

F

F

A

L

L

A

D

E

V

I

L

C

A

G

A

A

A

V

A

I

D

E

A

A

G

G

A

A

E

T

R

T

L

I

V

N

L

I

C

P

D

D

T

T

N

V

G

G

G

Y

T

S

L

I

P

P

D

Y

D

K

V

T

G

E

P

E

I

F

V

F

D

R

D

E

V

L

R

I

A

A

A

-

V

-

A

K

T

T

P

P

L

N

G

G

-

G

-

K

-

V

-

W

-

S

V

A

H
|
H

F

C

H
|
H

N

N

D

D

S

L

G

G

C

L

A

A

V

V

A

A

N

N

S

S

L

L

L

A

A

A

V

L

A

K

H

G

G

G

V

A

I

R

Q

Q

V

V

Q

E

G

C

C

T

M

V

N

N

G

G

Y

L

G

G

E

E

R

R

T

A

G

G

N
|
N

A

A

N

S

L

V

V

E

P

E

V

I

I

V

A

M

G

A

L

L

S

K

L

V

K

R

R

H

S

D

V

L

R

F

T

G

I

L

P

E

P

T

E

G

-

I

N

D

L

T

E

T

L

Q

L

I

T

V

T

P

V

S

S

S

R

K

H

L

I

V

A

S

E

T

L

I

T

T

N

G

Q

Y

P

P

L

V

P

Q

P

P

Q

N

S

K

P

A

Y

I

V

V

G

G

A

A

S

N

A

A

F

F

T

S

H

H

K

E

active site: Q16 (= Q21)
binding manganese (ii) ion: D13 (= D18), H201 (= H211), H203 (= H213), N237 (= N247)

3mi3A Homocitrate synthase lys4 bound to lysine (see paper)
26% identity, 68% coverage: 11:370/530 of query aligns to 14:350/370 of 3mi3A

query
sites
3mi3A

I

I

Y

I

D

E

T

S

T

T

L

L

R
|
R

D
x
E

G

G

S

E

Q
|
Q

Q

F

E

A

G

N

I

A

S

F

L

F

S

D

V

T

D

E

D

K

K

K

L

I

K

Q

V

I

A

A

R

K

Q

A

L

L

D

D

A

N

L

F

G

G

V

V

H

D

Y

Y

I

I

E

E

G

L

G

T

W

S

P

P

G

V

A

A

N

S

P

E

K

Q

D

S

A

R

A

Q

F

D

F

-

A

C

R

E

A

A

R

I

D

C

E

K

L

L

A

G

L

L

H

K

T

C

A

K

Q

I

L

L

V

-

A

-

F

-

G

-

S

-

T

-

R

-

A

T

S

H

T

I

T

R

A

C

E

H

S

M

D

D

P

D

N

A

L

R

A

V

A

A

L

V

T

E

N

T

A

G

G

V

V

D

G

G

L

V

A
x
D

C

V

I

V

V

I

A

G

K

-

A

-

W

-

D

-

V

-

H

-

V

-

I

-

H

-

A

-

L

-

R

-

T

T

S

S

L

M

P

T

E

Y

A

I

V

I

A

D

M

S

V

A

A

T

D

E

S

V

V

I

R

N

W

F

L

V

V

K

D

S

H

K

G

G

I

I

R

E

V

V

M

R

L

F

D

S

A

S

E

E

H

-

F

-

D

D

G

S

W

F

R

R

H

S

D

D

R

L

S

V

F

D

A

L

L

L

D

S

V

L

L

Y

A

K

A

A

A

V

A

D

D

K

A

I

G

G

A

V

E

N

R

R

L

V

V

G

L

I

C

A

D

D

T
|
T

N

V

G

G

G

C

T

A

L

T

P

P

D

R

D

Q

V

V

G

Y

P

D

I

L

V

I

D

R

D

T

V

L

R

R

A

G

A

V

V

V

A

S

T

C

P

D

L

I

G

E

V

C

H
|
H

F

F

H
|
H

N

N

D

D

S

T

G

G

C

M

A

A

V

I

A

A

N

N

S

A

L

Y

L

C

A

A

V

L

A

E

H

A

G

G

V

A

I

T

Q

H

V

I

Q

D

G

T

C

S

M

I

N

L

G

G

Y

I

G

G

E

E

R

R

T

N

G

G

N

I

A

T

N

P

L

L

V

G

P

A

V

L

I

L

A

A

G

R

L

M

S

Y

L

V

K

T

R

D

S

R

V

E

R

Y

T

I

I

T

P

H

P

K

E

Y

N

K

L

L

E

N

L

Q

L

L

T

R

T

E

V

L

S

E

R

N

H

L

I

V

A

A

E

D

L

A

T

V

N

E

Q

V

P

Q

L

I

P

P

P

F

Q

N

S

N

P

Y

Y

I

V

T

G

G

A

M

S

C

A

A

F

F

T

T

H

H

K

K

A

A

G

G

L

I

H

H

V

A

S

K

A

A

I

I

A

L

R

A

R

N

R

P

D

S

A

T

Y

Y

E

E

H

I

I

L

D

K

P

P

T

E

L

D

V

F

G

G

N

-

T

M

T

S

R

R

F

Y

V

V

V

H

-

V

-

G

S

S

E

R

M

L

A

T

G

G

R

W

Q

N

S

A

I

I

Q

K

L

S

K

R

A

A

T

E

Q

Q

L

L

G

N

I

L

D

H

L

L

G

T

E

D

D

A

D

Q

I

A

A

K

E

E

V

L

L

T

R

V

R

R

L

I

K

K

D

K

L

L

active site: Q24 (= Q21)
binding lysine: R20 (= R17), D100 (≠ A106), T163 (= T184), H190 (= H211), H192 (= H213)
binding zinc ion: E21 (≠ D18), H190 (= H211), H192 (= H213)

Q9Y823 Homocitrate synthase, mitochondrial; HCS; EC 2.3.3.14 from Schizosaccharomyces pombe (strain 972 / ATCC 24843) (Fission yeast) (see 2 papers)
26% identity, 68% coverage: 11:370/530 of query aligns to 37:384/418 of Q9Y823

query
sites
Q9Y823

I

I

Y

I

D

E

T

S

T

T

L

L

R
|
R

D
x
E

G

G

S

E

Q
|
Q

Q

F

E

A

G

N

I

A

S

F

L

F

S

D

V

T

D

E

D

K

K

K

L

I

K

Q

V

I

A

A

R

K

Q

A

L

L

D

D

A

N

L

F

G

G

V

V

H

D

Y

Y

I

I

E
|
E

G

L

G

T

W

S

P

P

G

V

A

A

N

S

P

E

K

Q

D

S

A

R

A

Q

F

D

F

-

A

C

R

E

A

A

R

I

D

C

E

K

L

L

A

G

L

L

H

K

T

C

A

K

Q

I

L

L

V

T

A
x
H

F

I

G

-

S

-

T

-

R

-

A

-

S

-

T

-

T

R

A

C

E

H

S

M

D

D

P

D

N

A

L

R

A

V

A

A

L

V

T

E

N

T

A

G

G

V

V

D

G

G

L

V

A
x
D

C

V

I

V

V

I

A

G

K

T

A

S

W

Q

D

-

V

-

H

-

V

-

I

-

H

Y

A

L

L

R

R

K

T

Y

S

S

L

H

P

G

E

K

A

D

V

M

A

T

M

Y

V

I

A

I

D

D

S

S

-

A

-

T

-

E

-

V

V

I

R

N

W

F

L

V

V

K

D

S

H

K

G

G

I

I

R

E

V

V

M
x
R

L

F

D
x
S

A

S

E
|
E

H

-

F

-

D

D

G

S

W

F

R

R

H

S

D

D

R

L

S

V

F

D

A

L

L

L

D

S

V

L

L

Y

A

K

A

A

A

V

A

D

D

K

A

I

G

G

A

V

E

N

R

R

L

V

V

G

L

I

C

A

D

D

T
|
T

N

V

G

G

G

C

T

A

L

T

P

P

D

R

D

Q

V

V

G

Y

P

D

I

L

V

I

D

R

D

T

V

L

R

R

A

G

A

V

V

V

A

S

T

C

P

D

L

I

G
x
E

V

C

H
|
H

F

F

H
|
H

N

N

D

D

S

T

G

G

C

M

A

A

V

I

A

A

N

N

S

A

L

Y

L

C

A

A

V

L

A

E

H

A

G

G

V

A

I

T

Q

H

V

I

Q

D

G

T

C

S

M

I

N

L

G

G

Y

I

G

G

E

E

R

R

T

N

G

G

N

I

A

T

N

P

L

L

V

G

P

A

V

L

I

L

A

A

G

R

L

M

S

Y

L

V

K

T

R

D

S

R

V

E

R

Y

T

I

I

T

P

H

P

K

E

Y

N

K

L

L

E

N

L

Q

L

L

T
x
R

T

E

V

L

S

E

R

N

H

L

I

V

A

A

E

D

L

A

T

V

N

E

Q

V

P

Q

L

I

P

P

P

F

Q

N

S

N

P

Y

Y

I

V

T

G

G

A

M

S

C

A

A

F

F

T

T

H

H

K

K

A

A

G

G

L

I

H

H

V

A

S

K

A

A

I

I

A

L

R

A

R

N

R

P

D

S

A

T

Y
|
Y

E

E

H

I

I

L

D

K

P

P

T

E

L

D

V

F

G

G

N

-

T

M

T

S

R

R

F

Y

V

V

V

H

-

V

-

G

S

S

E

R

M

L

A

T

G

G

R

W

Q

N

S

A

I

I

Q

K

L

S

K

R

A

A

T

E

Q
|
Q

L

L

G

N

I

L

D

H

L

L

G

T

E

D

D

A

D

Q

I

A

A

K

E

E

V

L

L

T

R

V

R

R

L

I

K

K

D

K

L

L

R43 (= R17) binding 2-oxoglutarate; mutation R->A,K,Q: Abolishes the catalytic activity.
E44 (≠ D18) binding 2-oxoglutarate; binding L-lysine; binding Zn(2+)
Q47 (= Q21) mutation to A: Abolishes the catalytic activity.
E74 (= E48) mutation to A: Abolishes the catalytic activity.; mutation to Q: Results in a moderate decrease in the turnover number and a slight increase in the Km value for each substrate.
H103 (≠ A78) binding 2-oxoglutarate; mutation to A: Substantially impairs catalytic efficiency.
D123 (≠ A106) binding L-lysine; mutation to N: Does not affect the catalytic activity but impairs L-lysine inhibition.
R163 (≠ M147) binding 2-oxoglutarate; mutation R->A,Q: Abolishes the catalytic activity.; mutation to K: Severely diminishes affinity for 2-oxoglutarate and substantially impairs catalytic efficiency.
S165 (≠ D149) binding 2-oxoglutarate; mutation to A: Results in a moderate decrease in catalytic efficiency.
E167 (= E151) mutation E->A,Q: Abolishes the catalytic activity.
T197 (= T184) binding 2-oxoglutarate; binding L-lysine; mutation to A: Exhibits a 25-fold decrease in catalytic efficiency.; mutation to S: Results in a modest decrease in catalytic efficiency.; mutation to V: Abolishes the catalytic activity.
E222 (≠ G209) mutation to Q: Does not affect the catalytic activity but impairs L-lysine inhibition.
H224 (= H211) binding 2-oxoglutarate; binding Zn(2+)
H226 (= H213) binding 2-oxoglutarate; binding Zn(2+)
R288 (≠ T275) mutation to K: Does not affect the catalytic activity but impairs L-lysine inhibition.
Y332 (= Y319) mutation to A: Abolishes the catalytic activity.; mutation to F: Results in a decrease in catalytic efficiency.
Q364 (= Q350) mutation to R: Does not affect the catalytic activity but impairs L-lysine inhibition.

3ivtB Homocitrate synthase lys4 bound to 2-og (see paper)
26% identity, 68% coverage: 11:370/530 of query aligns to 32:379/400 of 3ivtB

query
sites
3ivtB

I

I

Y

I

D

E

T

S

T

T

L

L

R
|
R

D
x
E

G

G

S

E

Q
|
Q

Q

F

E

A

G

N

I

A

S

F

L

F

S

D

V

T

D

E

D

K

K

K

L

I

K

Q

V

I

A

A

R

K

Q

A

L

L

D

D

A

N

L

F

G

G

V

V

H

D

Y

Y

I

I

E

E

G

L

G

T

W

S

P

P

G

V

A

A

N

S

P

E

K

Q

D

S

A

R

A

Q

F

D

F

-

A

C

R

E

A

A

R

I

D

C

E

K

L

L

A

G

L

L

H

K

T

C

A

K

Q

I

L

L

V

-

A

-

F

-

G

-

S

-

T

-

R

-

A

T

S
x
H

T

I

T

R

A

C

E

H

S

M

D

D

P

D

N

A

L

R

A

V

A

A

L

V

T

E

N

T

A

G

G

V

V

D

G

G

L

V

A

D

C

V

I

V

V

I

A

G

K

T

A

S

W

Q

D

-

V

-

H

-

V

-

I

-

H

Y

A

L

L

R

R

K

T

Y

S

S

L

H

P

G

E

K

A

D

V

M

A

T

M

Y

V

I

A

I

D

D

S

S

-

A

-

T

-

E

-

V

V

I

R

N

W

F

L

V

V

K

D

S

H

K

G

G

I

I

R

E

V

V

M
x
R

L

F

D
x
S

A

S

E

E

H

-

F

-

D

D

G

S

W

F

R

R

H

S

D

D

R

L

S

V

F

D

A

L

L

L

D

S

V

L

L

Y

A

K

A

A

A

V

A

D

D

K

A

I

G

G

A

V

E

N

R

R

L

V

V

G

L

I

C

A

D

D

T
|
T

N

V

G

G

G

C

T

A

L

T

P

P

D

R

D

Q

V

V

G

Y

P

D

I

L

V

I

D

R

D

T

V

L

R

R

A

G

A

V

V

V

A

S

T

C

P

D

L

I

G

E

V

C

H
|
H

F

F

H
|
H

N

N

D

D

S

T

G

G

C

M

A

A

V

I

A

A

N

N

S

A

L

Y

L

C

A

A

V

L

A

E

H

A

G

G

V

A

I

T

Q

H

V

I

Q

D

G

T

C

S

M

I

N

L

G

G

Y

I

G

G

E

E

R

R

T

N

G

G

N

I

A

T

N

P

L

L

V

G

P

A

V

L

I

L

A

A

G

R

L

M

S

Y

L

V

K

T

R

D

S

R

V

E

R

Y

T

I

I

T

P

H

P

K

E

Y

N

K

L

L

E

N

L

Q

L

L

T

R

T

E

V

L

S

E

R

N

H

L

I

V

A

A

E

D

L

A

T

V

N

E

Q

V

P

Q

L

I

P

P

P

F

Q

N

S

N

P

Y

Y

I

V

T

G

G

A

M

S

C

A

A

F

F

T

T

H

H

K

K

A

A

G

G

L

I

H

H

V

A

S

K

A

A

I

I

A

L

R

A

R

N

R

P

D

S

A

T

Y

Y

E

E

H

I

I

L

D

K

P

P

T

E

L

D

V

F

G

G

N

-

T

M

T

S

R

R

F

Y

V

V

V

H

-

V

-

G

S

S

E

R

M

L

A

T

G

G

R

W

Q

N

S

A

I

I

Q

K

L

S

K

R

A

A

T

E

Q

Q

L

L

G

N

I

L

D

H

L

L

G

T

E

D

D

A

D

Q

I

A

A

K

E

E

V

L

L

T

R

V

R

R

L

I

K

K

D

K

L

L

active site: Q42 (= Q21)
binding 2-oxoglutaric acid: R38 (= R17), H98 (≠ S86), R158 (≠ M147), S160 (≠ D149), T192 (= T184), H219 (= H211), H221 (= H213)
binding zinc ion: E39 (≠ D18), H219 (= H211), H221 (= H213)

3ivsA Homocitrate synthase lys4 (see paper)
25% identity, 67% coverage: 11:367/530 of query aligns to 14:345/364 of 3ivsA

query
sites
3ivsA

I

I

Y

I

D

E

T

S

T

T

L

L

R

R

D
x
E

G

G

S

E

Q
|
Q

Q

F

E

A

G

N

I

A

S

F

L

F

S

D

V

T

D

E

D

K

K

K

L

I

K

Q

V

I

A

A

R

K

Q

A

L

L

D

D

A

N

L

F

G

G

V

V

H

D

Y

Y

I

I

E

E

G

L

G

T

W

S

P

P

G

V

A

A

N

S

P

E

K

Q

-

S

-

R

-

Q

D

D

A

C

A

E

F

A

F

I

A

C

R

K

A

L

R

G

D

L

E

K

L

C

A

K

L

I

H

L

T

T

A

H

Q

I

L

R

V

C

A

H

F

M

G

D

S

D

T

A

R

R

R

V

A

A

S

V

T

E

T

T

A

G

E

V

S

D

D

G

P

V

N

D

L

V

A

V

A

-

L

-

T

-

N

-

A

-

G

-

V

I

G

G

L

T

A

T

C

Y

I

I

V

I

A

D

K

S

A

A

W

T

D

E

V

V

H

-

V

-

I

-

H

-

A

-

L

-

R

-

T

-

S

-

L

-

P

-

E

-

A

-

V

-

A

-

M

-

V

-

A

-

D

-

S

-

V

I

R

N

W

F

L

V

V

K

D

S

H

K

G

G

I

I

R

E

V

V

M

R

L

F

D

S

A

S

E

E

H

-

F

-

D

D

G

S

W

F

R

R

H

S

D

D

R

L

S

V

F

D

A

L

L

L

D

S

V

L

L

Y

A

K

A

A

A

V

A

D

D

K

A

I

G

G

A

V

E

N

R

R

L

V

V

G

L

I

C

A

D

D

T

T

N

V

G

G

G

C

T

A

L

T

P

P

D

R

D

Q

V

V

G

Y

P

D

I

L

V

I

D

R

D

T

V

L

R

R

A

G

A

V

V

V

A

S

T

C

P

D

L

I

G

E

V

C

H
|
H

F

F

H
|
H

N

N

D

D

S

T

G

G

C

M

A

A

V

I

A

A

N

N

S

A

L

Y

L

C

A

A

V

L

A

E

H

A

G

G

V

A

I

T

Q

H

V

I

Q

D

G

T

C

S

M

I

N

L

G

G

Y

I

G

G

E

E

R

R

T

N

G

G

N

I

A

T

N

P

L

L

V

G

P

A

V

L

I

L

A

A

G

R

L

M

S

Y

L

V

K

T

R

D

S

R

V

E

R

Y

T

I

I

T

P

H

P

K

E

Y

N

K

L

L

E

N

L

Q

L

L

T

R

T

E

V

L

S

E

R

N

H

L

I

V

A

A

E

D

L

A

T

V

N

E

Q

V

P

Q

L

I

P

P

P

F

Q

N

S

N

P

Y

Y

I

V

T

G

G

A

M

S

C

A

A

F

F

T

T

H

H

K

K

A

A

G

G

L

I

H

H

V

A

S

K

A

A

I

I

A

L

R

A

R

N

R

P

D

S

A

T

Y

Y

E

E

H

I

I

L

D

K

P

P

T

E

L

D

V

F

G

G

N

-

T

M

T

S

R

R

F

Y

V

V

V

H

-

V

-

G

S

S

E

R

M

L

A

T

G

G

R

W

Q

N

S

A

I

I

Q

K

L

S

K

R

A

A

T

E

Q

Q

L

L

G

N

I

L

D

H

L

L

G

Q

E

A

D

K

D

E

I

L

A

T

E

V

V

R

L

I

R

K

L

L

active site: Q24 (= Q21)
binding cobalt (ii) ion: E21 (≠ D18), H188 (= H211), H190 (= H213)

3bliA Crystal structure of the catalytic domain of licms in complexed with pyruvate and acetyl-coa (see paper)
26% identity, 57% coverage: 9:311/530 of query aligns to 2:299/311 of 3bliA

query
sites
3bliA

V

L

E

E

I

I

Y

L

D

D

T

V

T

T

L

L

R
|
R

D
|
D

G

G

S

E

Q
|
Q

Q

T

E

R

G

G

I

V

S

S

L

F

S

S

V

T

D

S

D

E

K

K

L

L

K

N

V

I

A

A

R

K

-

F

Q

L

L

L

D

Q

A

K

L

L

G

N

V

V

H

D

Y

R

I

V

E

E

G

I

G

A

W

S

P

A

G
x
R

A
x
V

N

S

P

K

K

G

D

E

A

L

A

E

F

T

F

V

A

Q

R

K

A

I

R

M

D

E

E

W

L

A

A

A

L

-

H

-

T

T

A

E

Q

Q

L

L

V

-

A

-

F

-

G

-

S

-

T

T

R

E

R

R

A

I

S

E

T

I

T

L

A

G

E

F

S

V

D

D

P

G

N

N

L

K

A

T

A

V

-

D

-

W

L

I

T

K

N

D

A

S

G

G

V

A

G

K

L

V

A

L

C

N

I

L

V

L

A

T

K

K

A

G

W

S

D

L

V

H

H

H

V

L

I

E

H

K

A

Q

L

L

R

G

T

K

S

T

L

P

P

K

E

E

A

F

V

F

A

T

M

D

V

V

A

S

D

F

S

V

V

I

R

E

W

Y

L

A

V

I

D

K

H

S

G

G

I

L

R

K

V

I

M

N

L

V

D
x
Y

A

L

E
|
E

H

D

F

W

F

S

D

N

G

G

W

F

R

R

H

N

D

S

R

P

S

D

F

Y

A

V

L

K

D

S

V

L

L

V

A

E

A

H

A

L

A

S

D

K

A

E

G

H

A

I

E

E

R

R

L

I

V

F

L

L

C
x
P

D

D

T
|
T

N

L

G

G

G

V

T

L

L

S

P

P

D

E

V

T

G

F

P

Q

I

G

V

V

D

D

D

S

-

L

V

I

R

Q

A

K

A

Y

V

P

A

D

T

I

P

H

L

F

G

E

V

F

H
|
H

F

G

H
|
H

N

N

D

D

S

Y

G

D

C

L

A

S

V

V

A

A

N

N

S

S

L

L

L

Q

A

A

V

I

A

R

H

A

G

G

V

V

I

K

Q

G

V

L

Q

H

G

A

C

S

M

I

N

N

G

G

Y

L

G

G

E

E

R

R

T

A

G

G

N

N

A

T

N

P

L

L

V

E

P

A

V

L

I

V

A

T

G

T

L

I

S

H

L

D

K

K

R

S

S

N

V

S

R

K

T

T

I

N

P

I

P

N

E

E

N

I

L

-

E

-

L

A

L

I

T

T

T

E

V

A

S

S

R

R

H

L

I

V

A

E

E

V

L

F

T

S

N

G

Q

K

P

R

L

I

P

S

P

A

Q

N

S

R

P

P

Y

I

V

V

G

G

A

E

S

D

A

V

F

F

T

T

H

Q

K

T

A

A

G

G

L

V

H

N

V

L

S

Y

A

A

active site: Q14 (= Q21)
binding acetyl coenzyme *a: Q14 (= Q21), R47 (≠ G53), V48 (≠ A54), E140 (= E151)
binding pyruvic acid: R10 (= R17), Y138 (≠ D149), P171 (≠ C182), T173 (= T184)
binding zinc ion: D11 (= D18), H201 (= H211), H203 (= H213)

P9WQB3 2-isopropylmalate synthase; Alpha-IPM synthase; Alpha-isopropylmalate synthase; EC 2.3.3.13 from Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv) (see 2 papers)
27% identity, 45% coverage: 208:448/530 of query aligns to 282:542/644 of P9WQB3

query
sites
P9WQB3

L
|
L

G
x
S

V
x
L

H
|
H

F
x
P

H
|
H

N
|
N

D
|
D

S
x
R

G
|
G

C
x
T

A
|
A

V
|
V

A
|
A

N
x
A

S
x
A

L
x
E

L
|
L

A
x
G

V
x
F

A
|
A

H
x
A

G
|
G

V
x
A

I
x
D

Q
x
R

V
x
I

Q
x
E

G
|
G

C
|
C

M
x
L

N
x
F

G
|
G

Y
x
N

G
|
G

E
|
E

R
|
R

T
|
T

G
|
G

N
|
N

A
x
V

N
x
C

L
|
L

V
|
V

P

-

V

-

I

-

A

-

G
x
T

L
|
L

S
x
G

L
|
L

K
x
N

R
x
L

S
x
F

V
x
S

R
|
R

T
x
G

I
x
V

P
x
D

P
|
P

E
x
Q

-
x
I

N
x
D

L
x
F

E
x
S

L
x
N

L
x
I

T
x
D

T
x
E

V
x
I

S
x
R

R
|
R

H
x
T

I
x
V

A
x
E

E
x
Y

L
x
C

T
x
N

N
x
Q

Q
x
L

P
|
P

L
x
V

P
x
H

P
x
E

Q
x
R

S
x
H

P
|
P

Y
|
Y

V
x
G

G
|
G

A
x
D

S
x
L

A
x
V

F
x
Y

T
|
T

H
x
A

K
x
F

A
x
S

G
|
G

L
x
S

H
|
H

V
x
Q

S
x
D

A
|
A

I
|
I

A
x
N

R
x
K

R
x
G

R
x
L

D
|
D

A
|
A

-
x
M

-
x
K

-
x
L

-
x
D

-
x
A

-
x
D

-
x
A

-
x
D

-
x
C

-
x
D

-
x
V

-
x
D

-
x
M

-
x
L

-
x
W

-
x
Q

-
x
V

-
x
P

Y
|
Y

E
x
L

H
x
P

I
|
I

D
|
D

P
|
P

T
x
R

L
x
D

V
|
V

G
|
G

N
x
R

T
|
T

T
x
Y

R
x
E

F
x
A

V
|
V

-
x
I

-
x
R

V
|
V

S
x
N

E
x
S

M
x
Q

A
x
S

G
|
G

R
x
K

Q
x
G

S
x
G

I
x
V

-
x
A

Q
x
Y

L
x
I

K
x
M

A
x
K

T
|
T

Q
x
D

L
x
H

G
|
G

I
x
L

D
x
S

L
|
L

G
x
P

-
x
R

-
x
L

E
x
Q

D
x
I

D
x
E

I
x
F

A
x
S

E
x
Q

V
|
V

L
x
I

R
x
Q

R
x
K

L
x
I

K
x
A

D
x
E

L

-

E

-

H

-

R

-

G
|
G

Y
x
T

H
x
A

F
x
G

E
|
E

A
x
G

D
x
E

G
x
V

S
|
S

L
x
P

E
x
K

L
x
E

L
x
M

L
x
W

R
x
D

R
x
A

A
x
F

S
x
A

G
x
E

W
x
E

T
x
Y

L
|
L

D
x
A

D
x
P

V
|
V

-
x
R

A
x
P

V
x
L

E
|
E

S
x
R

Y
x
I

R
|
R

T
x
Q

I
x
H

S
x
V

D
|
D

C
x
A

M
x
A

T
x
D

D
|
D

G
x
D

P
x
G

R
x
G

A
x
T

T
|
T

E
x
S

A
x
I

T
|
T

V
x
A

K
x
T

L
x
V

T
x
K

V
x
I

N
|
N

D
x
G

R
x
V

R
x
E

V
x
T

I
x
E

A
x
I

T
x
S

A
x
G

E
x
S

G
|
G

N
|
N

G
|
G

P
|
P

V
x
L

N
x
A

A
|
A

L
x
F

D
x
V

E
x
H

A
|
A

L
|
L

H285 (= H211) binding 3-methyl-2-oxobutanoate
H287 (= H213) binding 3-methyl-2-oxobutanoate
369:424 (vs. 298:333, 25% identical) Subdomain I
425:433 (vs. 334:340, 33% identical) Linker
434:490 (vs. 341:397, 13% identical) Subdomain II
N532 (= N438) binding L-leucine
A536 (≠ N442) binding L-leucine

Sites not aligning to the query:

51:368 N-terminal domain
80 binding 3-methyl-2-oxobutanoate
254 binding 3-methyl-2-oxobutanoate
426:644 Required for the condensation reaction. Not required to bind substrate
491:644 Regulatory domain
563 binding L-leucine
565 binding L-leucine
625 binding L-leucine
627 binding L-leucine

3figB Crystal structure of leucine-bound leua from mycobacterium tuberculosis (see paper)
24% identity, 82% coverage: 16:448/530 of query aligns to 62:510/577 of 3figB

query
sites
3figB

L

L

R

R

D
|
D

G

G

S

N

Q

Q

Q

A

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A

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binding leucine: G501 (= G439), P502 (= P440), L503 (≠ V441), A504 (≠ N442)
binding zinc ion: D64 (= D18), H268 (= H211), H270 (= H213)

Sites not aligning to the query:

binding leucine: 531, 533, 558, 560

Query Sequence

>WP_015798940.1 NCBI__GCF_000023265.1:WP_015798940.1
MSAGFPAEVEIYDTTLRDGSQQEGISLSVDDKLKVARQLDALGVHYIEGGWPGANPKDAA
FFARARDELALHTAQLVAFGSTRRASTTAESDPNLAALTNAGVGLACIVAKAWDVHVIHA
LRTSLPEAVAMVADSVRWLVDHGIRVMLDAEHFFDGWRHDRSFALDVLAAAADAGAERLV
LCDTNGGTLPDDVGPIVDDVRAAVATPLGVHFHNDSGCAVANSLLAVAHGVIQVQGCMNG
YGERTGNANLVPVIAGLSLKRSVRTIPPENLELLTTVSRHIAELTNQPLPPQSPYVGASA
FTHKAGLHVSAIARRRDAYEHIDPTLVGNTTRFVVSEMAGRQSIQLKATQLGIDLGEDDI
AEVLRRLKDLEHRGYHFEAADGSLELLLRRASGWTLDDVAVESYRTISDCMTDGPRATEA
TVKLTVNDRRVIATAEGNGPVNALDEALRAALDPAFPLLKTVKLTDFKVRVLDSDQGTDA
TVRVLIDFQDPEDTWTTTGVSTNVIDASFEALLDGLIVAIARARDRGEEW

Or try a new SitesBLAST search

SitesBLAST's Database

SitesBLAST's database includes (1) SwissProt entries with experimentally-supported functional features; and (2) protein structures with bound ligands, from the BioLip database.

by Morgan Price, Arkin group
Lawrence Berkeley National Laboratory