SitesBLAST

SitesBLAST – Find functional sites

SitesBLAST

Comparing WP_018123594.1 NCBI__GCF_000375485.1:WP_018123594.1 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)
29% identity, 84% coverage: 2:447/533 of query aligns to 5:439/517 of Q9JZG1

query
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Q9JZG1

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D16 (= D13) binding Mn(2+)
H204 (= H206) binding Mn(2+)
H206 (= H208) binding Mn(2+)
N240 (= N242) binding Mn(2+)

Sites not aligning to the query:

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

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: 3:365/533 of query aligns to 21:370/399 of 6ktqA

query
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6ktqA

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binding 2-oxoglutaric acid: R30 (= R12), R154 (≠ F141), T156 (≠ D143), E158 (= E145), S184 (≠ V174), T188 (= T178), H216 (= H206), H218 (= H208)
binding coenzyme a: V67 (≠ S49), R96 (≠ K80), A97 (= A81), F116 (= F103), H128 (≠ L115), E158 (= E145)
binding zinc ion: E31 (≠ D13), H216 (= H206), H218 (= H208)

Q9FG67 Methylthioalkylmalate synthase 1, chloroplastic; 2-isopropylmalate synthase 3; EC 2.3.3.17 from Arabidopsis thaliana (Mouse-ear cress) (see paper)
29% identity, 72% coverage: 4:388/533 of query aligns to 85:485/506 of Q9FG67

query
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Q9FG67

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L

A

V

E

T

A

S

S

S

F

D

E

E

L

I

M

S

F

L

H

E

K

K

I

L

S102 (≠ N21) mutation to F: In gsm1-1; loss of conversion of C3 to C4 glucosinolates.
A290 (≠ G204) mutation to T: In gsm1-2; loss of conversion of C3 to C4 glucosinolates.

6e1jA Crystal structure of methylthioalkylmalate synthase (bjumam1.1) from brassica juncea (see paper)
28% identity, 67% coverage: 4:360/533 of query aligns to 18:384/409 of 6e1jA

query
sites
6e1jA

I

V

A

R

I

V

Y

F

D

D

T

T

L

L

R

R

D
|
D

G

G

T

E

Q
|
Q

A

S

E

P

E

G

L

A

N

A

L

L

T

T

T

P

K

P

D

Q

K

K

V

I

R

E

I

I

A

A

A

R

K

Q

L

L

D

A

E

K

L

L

G

R

V

V

H

D

Y

I

I

M

E

E

G

V

G

G

W
x
F

P

P

G

V

S
|
S

N

S

P

E

T

E

D

E

-

F

-

E

-

T

-

I

-

Q

-

T

-

I

-

A

K

K

Q

T

F

V

F

G

D

N

E

E

I
x
V

A

D

E
|
E

H

E

T

T

F

G

K

Y

N

I

A

P

S

V

I

I

A

C

A

V

F
x
I

G

A

S
x
R

T

S

F

-

N

-

P

-

K

-

A

K

D

E

P

R

D

D

S

I

D

K

P

A

I

A

F

W

Q

E

S

S

L

V

L

K

T

Y

C

A

G

K

A

R

E

P

V

R

F

I

T

V

I

I

F
|
F

G

T

K

S

T

T

W

S

D

D

L

I

H

H

A

L

T

K

L

Y

A
x
K

L
|
L

N

K

I

M

D

T

T

R

E

E

R

E

N

V

I

V

E

D

I

M

I

V

R

A

Q

S

S

S

V

I

A

R

H

F

L

A

R

K

P

S

H

L

A

G

R

F

E

E

-

D

V

I

F

E

F

F

D

G

A

C

E

E

H

-

F

-

D

D

G

G

F

G

R

R

A

S

N

D

P

K

E

D

F

Y

A

I

L

C

S

T

C

V

L

F

E

E

A

E

A

A

H

I

E

K

A

A

G

G

A

A

D

T

V

T

L

L

V

A

L

C

C
x
P

D

D

T
|
T

N

V

G

G

G

I

S

N

L

M

P

P

Y

H

Q

E

I

Y

A

G

E

K

G

L

V

V

N

R

A

Y

V

I

R

K

T

A

R

N

I

T

P

P

-

G

-

I

-

D

N

D

A

V

A

I

V

F

G

S

I

A

H
|
H

A

C

H
|
H

N

N

D

D

G

L

E

G

L

V

A

A

V

T

A

A

N

N

S

T

L

I

E

A

A

G

I

I

R

C

H

A

G

G

A

A

V

R

H

Q

V

V

Q

E

G

V

T

T

M

I

N

N

G

G

Y

I

G

G

E

E

R

R

C

S

G

G

N

N

A

A

N

P

L

L

C

E

S

E

I

V

P

M

N

A

L

L

E

K

L

C

K

R

L

G

G

A

M

F

E

V

S

M

I

G

G

G

A

V

E

Y

-

T

-

R

-

I

N

D

M

T

S

R

R

Q

L

I

T

M

E

A

V

T

S

S

H

K

Y

M

I

V

S

Q

E

E

I

Y

A

T

N

G

L

L

R

Y

P

V

F

Q

M

P

R

H

Q

K

P

P

F

I

V

V

G

G

A

A

S

N

A

C

F

F

A

V

H

H

K

E

G
x
S

G
|
G

V
x
I

H

H

V

Q

S
x
D

A

G

V

I

R

L

K
|
K

D

N

S

R

R

S

T

T

Y

Y

E

E

H

I

I

I

K

S

P

P

T

E

D

D

V

V

G

G

N

V

M

V

Q

K

R

S

-

Q

-

N

-

S

-

G

V

I

L

V

L

L

S

G

D

K

L
|
L

A

S

G

G

R
|
R

S
x
H

N

A

L

V

L

K

H

G

K

R

A

L

E

K

Q

E

F

L

G

G

H

Y

P

-

L

-

E

E

K

I

G

S

D

D

P

E

R

K

L

L

D

N

Q

E

L

V

binding coenzyme a: Q30 (= Q16), F60 (≠ W46), S63 (= S49), I95 (≠ F73), R97 (≠ S75), F121 (= F103), K132 (≠ A114), L133 (= L115), S322 (≠ G300), G323 (= G301), I324 (≠ V302), D327 (≠ S305), K331 (= K309), L359 (= L333), R362 (= R336), H363 (≠ S337)
binding 4-(methylsulfanyl)-2-oxobutanoic acid: P192 (≠ C176), T194 (= T178), H225 (= H206), H227 (= H208)
binding manganese (ii) ion: D27 (= D13), V82 (≠ I60), E84 (= E62), H225 (= H206), H227 (= H208)

O87198 Homocitrate synthase; HCS; EC 2.3.3.14 from Thermus thermophilus (strain ATCC BAA-163 / DSM 7039 / HB27) (see paper)
30% identity, 68% coverage: 1:365/533 of query aligns to 1:353/376 of O87198

query
sites
O87198

M

M

H

R

R

E

I

W

A

K

I

I

Y

I

D

D

T

S

T

T

L

L

R
|
R

D
x
E

G

G

T

E

Q

Q

A

F

E

E

E

K

L

A

N

N

L

F

T

S

T

T

K

Q

D

D

K

K

V

V

R

E

I

I

A

A

A

K

K

A

L

L

D

D

E

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

S

A

N

S

P

P

T

Q

D

S

K

R

Q

K

F

D

F

A

D

E

E

V

I

L

A

A

E

S

H

L

T

G

F

L

K

K

N

A

A

K

S

V

I

V

A

T

A
x
H

F

I

G

Q

S

C

T

R

F

L

N

-

P

-

K

-

A

-

D

-

P

-

D

-

S

-

D

D

P

A

I

A

F

K

Q

V

S

A

L

V

L

E

T

T

C

G

G

V

A

Q

E

G

V

I

F
x
D

T

L

I

L

F

F

G

G

K

T

T

S

W

K

D

Y

L

L

H

R

A

A

T

-

L

-

A

A

L

H

N

G

I

R

D

D

T

I

E

P

R

R

N

I

I

I

E

E

I

E

I

A

R

K

Q

E

S

V

V

I

A

A

H

Y

L

I

R

R

-

E

-

A

P

P

H

H

A

V

R

-

E

E

V

V

F
x
R

F

F

D
x
S

A

A

E

E

H

-

F

-

D

D

G

T

F

F

R

R

A

S

N

E

P

E

E

Q

F

D

A

L

L

L

S

A

C

V

L

Y

E

E

A

A

A

V

H

A

E

P

A

Y

G

-

A

V

D

D

V

R

L

V

V

G

L

L

C

A

D

D

T
|
T

N

V

G

G

G

V

S

A

L

T

P

P

Y

R

Q

Q

I

V

A

Y

E

A

G

L

V

V

N

R

A

E

V

V

R

R

T

R

R

V

I

V

-

G

P

P

N

R

A

V

A

D

V

I

G

E

I

F

H
|
H

A

G

H
|
H

N

N

D

D

G

T

E

G

L

C

A

A

V

I

A

A

N

N

S

A

L

Y

E

E

A

A

I

I

R

E

H

A

G

G

A

A

V

T

H

H

V

V

Q

D

G

T

T

T

M

I

N

L

G

G

Y

I

G

G

E

E

R

R

C

N

G

G

N

I

A

T

N

P

L

L

C

G

S

G

I

F

I

L

P

A

N

R

L

M

E

-

L

Y

K

T

L

L

G

Q

M

P

E

E

S

Y

I

V

G

R

A

R

E

K

-

Y

N

K

M

L

S

E

R

M

L

L

T

P

E

E

V

L

S

D

H

R

Y

M

I

V

S

A

E

R

I

M

A

V

N

G

L

V

R

E

P

I

F

P

M

F

R

N

Q

N

P

Y

F

I

V

T

G

G

A

E

S

T

A

A

F

F

A

S

H

H

K

K

G

A

G

G

V

M

H

H

V

L

S

K

A

A

V

I

R

Y

K

I

D

N

S

P

R

E

T

A

Y

Y

E

E

H

P

I

Y

K

P

P

P

T

E

D

V

V

F

G

G

N

V

M

K

Q

R

R

K

V

L

L

I

-

A

S

S

D

R

L

L

A

T

G

G

R

R

S

H

N

A

L

I

L

K

H

A

K

R

A

A

E

E

Q

E

F

L

G

G

H

-

P

-

L

L

E

H

K

Y

G

G

D

E

P

E

R

E

L

L

D

H

Q

R

L

V

V

T

R

Q

E

H

L

I

K

K

R12 (= R12) binding 2-oxoglutarate
E13 (≠ D13) binding Mg(2+)
H72 (≠ A72) 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 (≠ F100) binding L-lysine
R133 (≠ F141) binding 2-oxoglutarate
S135 (≠ D143) binding L-lysine
T166 (= T178) binding 2-oxoglutarate; binding L-lysine
H195 (= H206) binding Mg(2+)
H197 (= H208) binding Mg(2+)

3rmjB Crystal structure of truncated alpha-isopropylmalate synthase from neisseria meningitidis (see paper)
30% identity, 56% coverage: 2:299/533 of query aligns to 2:295/308 of 3rmjB

query
sites
3rmjB

H

N

R

R

I

V

A

I

I

I

Y

F

D

D

T

T

L

L

R

R

D
|
D

G

G

T

E

Q
|
Q

A

S

E

P

E

G

L

A

N

A

L

M

T

T

T

K

K

E

D

E

K

K

V

I

R

R

I

V

A

A

A

R

K

Q

L

L

D

E

E

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

S

A

N

S

P

P

T

G

D

D

K

F

Q

E

F

A

F

V

D

N

E

A

I

I

A

A

E

K

H

-

T

T

F

I

K

T

N

K

A

S

S

T

I

V

A

C

A

S

F

L

G

S

S

R

T

A

F

I

N

-

P

-

K

-

A

-

D

E

P

R

D

D

S

I

D

R

P

Q

I

A

F

G

Q

E

S

A

L

V

L

A

T

P

C

A

G

P

A

K

E

K

V

R

F

I

T

H

I

T

F

F

G

I

K

A

T

T

W

S

D

P

L

I

H

H

A

M

T

E

L

Y

A

K

L

L

N

K

I

M

D

K

T

P

E

K

R

Q

N

V

I

I

E

E

I

A

R

V

Q

K

S

A

V

V

A

K

H

I

L

A

R

R

P

E

H

Y

A

T

R

D

E

D

V

V

F

E

F

F

D

S

A

C

E

E

H

-

F

-

D

D

G

A

F

L

R

R

A

S

N

E

P

I

E

D

F

F

A

L

L

A

S

E

C

I

L

C

E

G

A

A

A

V

H

I

E

E

A

A

G

G

A

A

D

T

V

T

L

I

V

N

L

I

C

P

D

D

T

T

N

V

G

G

G

Y

S

S

L

I

P

P

Y

Y

Q

K

I

T

A

E

E

E

G

F

V

F

N

R

A

E

V

L

R

I

T

A

R

K

I

T

P

P

N

N

A

G

V

K

G

V

I

V

-

W

-

S

-

A

H
|
H

A

C

H
|
H

N

N

D

D

G

L

E

G

L

L

A

A

V

V

A

A

N

N

S

S

L

L

E

A

A

A

I

L

R

K

H

G

G

G

A

A

V

R

H

Q

V

V

Q

E

G

C

T

T

M

V

N

N

G

G

Y

L

G

G

E

E

R

R

C

A

G

G

N
|
N

A

A

N

S

L

V

C

E

S

E

I

I

I

V

P

M

N

A

L

L

E

K

L

V

K

R

-

H

-

D

-

L

L

F

G

G

M

L

E

E

S

T

I

-

G

-

A

G

E

I

N

D

M

T

S

T

R

Q

L

I

T

V

E

P

V

S

S

S

H

K

Y

L

I

V

S

S

E

T

I

I

A

T

N

G

L

Y

R

P

P

V

F

Q

M

P

R

N

Q

K

P

A

F

I

V

V

G

G

A

A

S

N

A

A

F

F

A

S

H

H

K

E

active site: Q16 (= Q16)
binding manganese (ii) ion: D13 (= D13), H201 (= H206), H203 (= H208), N237 (= N242)

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)
28% identity, 65% coverage: 4:350/533 of query aligns to 85:443/503 of Q9FN52

query
sites
Q9FN52

I

V

A

R

I

V

Y

L

D

D

T

T

L

L

R

R

D

D

G

G

T

E

Q

Q

A

S

E

P

E

G

L

A

N

A

L

L

T

T

T

P

K

P

D

Q

K

K

V

L

R

E

I

I

A

A

A

R

K

Q

L

L

D

A

E

K

L

L

G

R

V

V

H

D

Y

I

I

M

E

E

G

V

G

G

W

F

P

P

G

V

S

S

N

S

P

E

T

E

D

E

-

F

-

E

-

A

-

I

-

K

-

T

-

I

-

A

K

K

Q

T

F

V

F

G

D

N

E

E

I

V

A

D

E

E

H

E

T

T

F

G

K

Y

N

V

A

P

S

V

I

I

A

C

A

G

F

I

G

A

S

R

T

C

F

-

N

-

P

-

K

-

A

K

D

K

P

R

D

D

S

I

D

E

P

A

I

T

F

W

Q

E

S

A

L

L

L

K

T

Y

C

A

G

K

A

R

E

P

V

R

F

V

T

M

I

L

F

F

G

T

K

S

T

T

W

S

D

E

L

I

H

H

A

M

T

K

L

Y

A

K

L

L

N

K

I

K

D

T

T

K

E

E

R

E

N

V

I

I

E

E

I

M

I

A

R

V

Q

N

S

S

V

V

A

K

H

Y

L

A

R

K

P

S

H

L

A

G

-

F

R

K

E

D

V

I

F

Q

F

F

D

G

A

C

E

E

H

-

F

-

D

D

G

G

F

G

R

R

A

T

N

E

P

K

E

D

F

F

A

I

L

C

S

K

C

I

L

L

E

G

A

E

A

S

H

I

E

K

A

A

G

G

A

A

D

T

V

T

L

V

V

G

L

F

C

A

D

D

T

T

N

V

G
|
G

G

I

S

N

L

M

P

P

Y

Q

Q

E

I

F

A

G

E

E

G

L

V

V

N

A

A

Y

V

V

R

I

T

E

R

N

I

T

P

P

N

G

A

A

-

D

-

I

A

V

V

F

G

A

I

I

H

H

A

C

H

H

N

N

D

D

G

L

E

G

L

V

A

A

V

T

A

A

N

N

S

T

L

I

E

S

A

G

I

I

R

C

H

A

G

G

A

A

V

R

H

Q

V

V

Q

E

G

V

T

T

M

I

N

N

G

G

Y

I

G

G

E

E

R

R

C

S

G

G

N

N

A

A

N

P

L

L

C

E

S

E

I

V

P

M

N

A

L

L

E

K

L

C

K

R

-

G

-

E

L

S

G

L

M

M

E

D

S

G

I

V

G

Y

A

T

E

K

N

I

M

D

S

S

R

R

-

Q

L

I

T

M

E

A

V

T

S

S

H

K

Y

M

I

V

S

Q

E

E

I

H

A

T

N

G

L

M

R

Y

P

V

F

Q

M

P

R

H

Q

K

P

P

F

I

V

V

G

G

A

D

S

N

A

C

F

F

A

V

H

H

K

E

G

S

G

G

V

I

H

H

V

Q

S

D

A

G

V

I

R

L

K

K

D

N

S

R

R

S

T

T

Y

Y

E

E

H

I

I

L

K

S

P

P

T

E

D

D

V

V

G

G

N

I

M

V

Q

K

R

S

-

E

-

N

-

S

-

G

V

I

L

V

L

L

S

G

D

K

L

L

A

S

G

G

R

R

S

H

N

A

L

V

L

K

H

D

K

R

A

L

E

K

Q

E

F

L

G

G

H

Y

P

E

L

I

G263 (= G180) mutation to E: In gsm2-1; loss of activity and lack of C6, C7 and C8 aliphatic glucosinolates.

2zyfA Crystal structure of homocitrate synthase from thermus thermophilus complexed with magnesuim ion and alpha-ketoglutarate (see paper)
29% identity, 62% coverage: 1:331/533 of query aligns to 1:314/314 of 2zyfA

query
sites
2zyfA

M

M

H

R

R

E

I

W

A

K

I

I

Y

I

D

D

T

S

T

T

L

L

R
|
R

D
x
E

G

G

T

E

Q
|
Q

A

F

E

E

E

K

L

A

N

N

L

F

T

S

T

T

K

Q

D

D

K

K

V

V

R

E

I

I

A

A

A

K

K

A

L

L

D

D

E

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

S

A

N

S

P

P

T

Q

D

S

K

R

Q

K

F

D

F

A

D

E

E

V

I

L

A

A

E

S

H

L

T

G

F

L

K

K

N

A

A

K

S

V

I

V

A

T

A
x
H

F

-

G

-

S

-

T

-

F

-

N

-

P

-

K

-

A

-

D

-

P

-

D

-

S

-

D

-

P

-

I

-

F

I

Q

Q

S

C

L

R

L

L

T

D

C

A

G

A

A

K

E

V

V

A

F

V

T

E

I

T

F

G

G

V

K

Q

T

G

W

I

D

D

L

L

H
x
L

A

F

T

G

L

T

A

S

L

K

N

G

I

R

D

D

T

I

E

P

R

R

N

I

I

I

E

E

I

E

I

A

R

K

Q

E

S

V

V

I

A

A

H

Y

L

I

R

R

-

E

-

A

P

P

H

H

A

V

R

-

E

E

V

V

F
x
R

F

F

D

S

A

A

E

E

H

-

F

-

D

D

G

T

F

F

R

R

A

S

N

E

P

E

E

Q

F

D

A

L

L

L

S

A

C

V

L

Y

E

E

A

A

A

V

H

A

E

P

A

Y

G

-

A

V

D

D

V

R

L

V

V

G

L

L

C

A

D

D

T
|
T

N

V

G

G

G

V

S

A

L

T

P

P

Y

R

Q

Q

I

V

A

Y

E

A

G

L

V

V

N

R

A

E

V

V

R

R

T

R

R

V

I

V

-

G

P

P

N

R

A

V

A

D

V

I

G

E

I

F

H
|
H

A

G

H
|
H

N

N

D

D

G

T

E

G

L

C

A

A

V

I

A

A

N

N

S

A

L

Y

E

E

A

A

I

I

R

E

H

A

G

G

A

A

V

T

H

H

V

V

Q

D

G

T

T

T

M

I

N

L

G

G

Y

I

G

G

E

E

R

R

C

N

G

G

N

I

A

T

N

P

L

L

C

G

S

G

I

F

I

L

P

A

N

R

L

M

E

-

L

Y

K

T

L

L

G

Q

M

P

E

E

S

Y

I

V

G

R

A

R

E

K

-

Y

N

K

M

L

S

E

R

M

L

L

T

P

E

E

V

L

S

D

H

R

Y

M

I

V

S

A

E

R

I

M

A

V

N

G

L

V

R

E

P

I

F

P

M

F

R

N

Q

N

P

Y

F

I

V

T

G

G

A

E

S

T

A

A

F

F

A

S

H

H

K

K

G

A

G

G

V

M

H

H

V

L

S

K

A

A

V

I

R

Y

K

I

D

N

S

P

R

E

T

A

Y

Y

E

E

H

P

I

Y

K

P

P

P

T

E

D

V

V

F

G

G

N

V

M

K

Q

R

R

K

V

L

L

I

S

A

active site: Q16 (= Q16)
binding 2-oxoglutaric acid: R12 (= R12), H72 (≠ A72), L94 (≠ H110), R127 (≠ F141), T160 (= T178), H189 (= H206)
binding magnesium ion: E13 (≠ D13), H189 (= H206), H191 (= H208)

2ztjA Crystal structure of homocitrate synthase from thermus thermophilus complexed with alpha-ketoglutarate (see paper)
29% identity, 62% coverage: 1:331/533 of query aligns to 1:312/312 of 2ztjA

query
sites
2ztjA

M

M

H

R

R

E

I

W

A

K

I

I

Y

I

D

D

T

S

T

T

L

L

R
|
R

D
x
E

G

G

T

E

Q
|
Q

A

F

E

E

E

K

L

A

N

N

L

F

T

S

T

T

K

Q

D

D

K

K

V

V

R

E

I

I

A

A

A

K

K

A

L

L

D

D

E

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

S

A

N

S

P

P

T

Q

D

S

K

R

Q

K

F

D

F

A

D

E

E

V

I

L

A

A

E

S

H

L

T

G

F

L

K

K

N

A

A

K

S

V

I

V

A

T

A
x
H

F

I

G

Q

S

C

T

R

F

L

N

-

P

-

K

-

A

-

D

-

P

-

D

-

S

-

D

D

P

A

I

A

F

K

Q

V

S

A

L

V

L

E

T

T

C

G

G

V

A

Q

E

G

V

I

F

D

T

L

I
x
L

F

F

G

G

K

T

T

G

W

R

D

D

L

I

H

-

A

-

T

-

L

-

A

-

L

-

N

-

I

-

D

-

T

-

E

P

R

R

N

I

I

I

E

E

I

E

I

A

R

K

Q

E

S

V

V

I

A

A

H

Y

L

I

R

R

-

E

-

A

P

P

H

H

A

V

R

-

E

E

V

V

F
x
R

F

F

D

S

A

A

E

E

H

-

F

-

D

D

G

T

F

F

R

R

A

S

N

E

P

E

E

Q

F

D

A

L

L

L

S

A

C

V

L

Y

E

E

A

A

A

V

H

A

E

P

A

Y

G

-

A

V

D

D

V

R

L

V

V

G

L

L

C
x
A

D

D

T
|
T

N

V

G

G

G

V

S

A

L

T

P

P

Y

R

Q

Q

I

V

A

Y

E

A

G

L

V

V

N

R

A

E

V

V

R

R

T

R

R

V

I

V

-

G

P

P

N

R

A

V

A

D

V

I

G

E

I

F

H
|
H

A

G

H
|
H

N

N

D

D

G

T

E

G

L

C

A

A

V

I

A

A

N

N

S

A

L

Y

E

E

A

A

I

I

R

E

H

A

G

G

A

A

V

T

H

H

V

V

Q

D

G

T

T

T

M

I

N

L

G

G

Y

I

G

G

E

E

R

R

C

N

G

G

N

I

A

T

N

P

L

L

C

G

S

G

I

F

I

L

P

A

N

R

L

M

E

-

L

Y

K

T

L

L

G

Q

M

P

E

E

S

Y

I

V

G

R

A

R

E

K

-

Y

N

K

M

L

S

E

R

M

L

L

T

P

E

E

V

L

S

D

H

R

Y

M

I

V

S

A

E

R

I

M

A

V

N

G

L

V

R

E

P

I

F

P

M

F

R

N

Q

N

P

Y

F

I

V

T

G

G

A

E

S

T

A

A

F

F

A

S

H

H

K

K

G

A

G

G

V

M

H

H

V

L

S

K

A

A

V

I

R

Y

K

I

D

N

S

P

R

E

T

A

Y

Y

E

E

H

P

I

Y

K

P

P

P

T

E

D

V

V

F

G

G

N

V

M

K

Q

R

R

K

V

L

L

I

S

A

active site: Q16 (= Q16)
binding 2-oxoglutaric acid: R12 (= R12), H72 (≠ A72), L94 (≠ I102), R125 (≠ F141), A156 (≠ C176), T158 (= T178), H187 (= H206), H189 (= H208)
binding copper (ii) ion: E13 (≠ D13), H187 (= H206), H189 (= H208)

3a9iA Crystal structure of homocitrate synthase from thermus thermophilus complexed with lys (see paper)
30% identity, 68% coverage: 6:365/533 of query aligns to 5:342/347 of 3a9iA

query
sites
3a9iA

I

I

Y

I

D

D

T

S

T

T

L

L

R
|
R

D
x
E

G

G

T

E

Q

Q

A

F

E

E

E

K

L

A

N

N

L

F

T

S

T

T

K

Q

D

D

K

K

V

V

R

E

I

I

A

A

A

K

K

A

L

L

D

D

E

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

S

A

N

S

P

P

T

Q

D

S

K

R

Q

K

F

D

F

A

D

E

E

V

I

L

A

A

E

S

H

L

T

G

F

L

K

K

N

A

A

K

S

V

I

V

A

T

A

H

F

I

G

Q

S

C

T

R

F

L

N

-

P

-

K

-

A

-

D

-

P

-

D

-

S

-

D

D

P

A

I

A

F

K

Q

V

S

A

L

V

L

E

T

T

C

G

G

V

A

Q

E

G

V

I

F
x
D

T

L

I

L

F

F

G

G

K

T

T

S

W

K

D

Y

L

L

H

-

A

-

T

-

L

-

A

-

L

-

N

-

I

-

D

D

T

I

E

P

R

R

N

I

I

I

E

E

I

E

I

A

R

K

Q

E

S

V

V

I

A

A

H

Y

L

I

R

R

-

E

-

A

P

P

H

H

A

V

R

-

E

E

V

V

F

R

F

F

D
x
S

A

A

E

E

H

-

F

-

D

D

G

T

F

F

R

R

A

S

N

E

P

E

E

Q

F

D

A

L

L

L

S

A

C

V

L

Y

E

E

A

A

A

V

H

A

E

P

A

Y

G

-

A

V

D

D

V

R

L

V

V

G

L

L

C

A

D

D

T
|
T

N

V

G

G

G

V

S

A

L

T

P

P

Y

R

Q

Q

I

V

A

Y

E

A

G

L

V

V

N

R

A

E

V

V

R

R

T

R

R

V

I

V

-

G

P

P

N

R

A

V

A

D

V

I

G

E

I

F

H
|
H

A

G

H
|
H

N

N

D

D

G

T

E

G

L

C

A

A

V

I

A

A

N

N

S

A

L

Y

E

E

A

A

I

I

R

E

H

A

G

G

A

A

V

T

H

H

V

V

Q

D

G

T

T

T

M

I

N

L

G

G

Y

I

G

G

E

E

R

R

C

N

G

G

N

I

A

T

N

P

L

L

C

G

S

G

I

F

I

L

P

A

N

R

L

M

E

-

L

Y

K

T

L

L

G

Q

M

P

E

E

S

Y

I

V

G

R

A

R

E

K

-

Y

N

K

M

L

S

E

R

M

L

L

T

P

E

E

V

L

S

D

H

R

Y

M

I

V

S

A

E

R

I

M

A

V

N

G

L

V

R

E

P

I

F

P

M

F

R

N

Q

N

P

Y

F

I

V

T

G

G

A

E

S

T

A

A

F

F

A

S

H

H

K

K

G

A

G

G

V

M

H

H

V

L

S

K

A

A

V

I

R

Y

K

I

D

N

S

P

R

E

T

A

Y

Y

E

E

H

P

I

Y

K

P

P

P

T

E

D

V

V

F

G

G

N

-

M

-

Q

-

R

-

V

-

L

-

L

V

S

K

D

G

L

L

A

H

G

Y

R

G

S

E

N

E

L

E

L

L

H

H

K

R

A

V

E

T

Q

Q

F

H

G

I

H

K

P

A

L

L

-

A

E

D

K

R

G

G

D

Q

P

L

R

T

L

L

D

E

Q

E

L

L

V

D

R

R

E

I

L

L

K

R

binding cobalt (ii) ion: E12 (≠ D13), H188 (= H206), H190 (= H208)
binding lysine: R11 (= R12), D91 (≠ F100), S128 (≠ D143), T159 (= T178), H188 (= H206), H190 (= H208)

4ov9A Structure of isopropylmalate synthase binding with alpha- isopropylmalate (see paper)
28% identity, 64% coverage: 4:346/533 of query aligns to 4:338/380 of 4ov9A

query
sites
4ov9A

I

I

A

H

I

I

Y

Q

D

D

T

V

T

T

L

L

R
|
R

D
|
D

G

G

T

N

Q
|
Q

A

A

E

L

E

K

L

R

N

P

L

W

T

T

T

I

K

D

D

E

K

K

V

I

R

E

I

V

A

F

A

D

K

L

L

L

D

V

E

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

S

S

N

N

P

E

T

T

D

E

K

F

Q

H

F

T

F

C

D

Q

E

V

I

L

A

S

E

K

H

R

T

A

F

P

K

K

N

G

A

K

S

P

I

I

A

A

F
x
L

G

S

S

-

T

-

F

-

N

-

P

-

K

R

A

A

D

N

P

Q

D

N

S

E

D

I

P

A

I

V

-

T

F

W

Q

E

S

A

L

I

L

Q

T

K

C

A

G

D

A

C

E

P

V

R

F

M

T

H

I

I

F

V

G

Y

K

P

T

V

W

S

D

D

L

F

H

S

A

I

T

K

L

H

A

V

L

L

N

K

I

I

D

S

T

E

E

K

R

E

N

V

I

L

E

Q

I

K

I

I

R

R

Q

N

S

S

V

I

A

S

H

F

L

A

R

R

P

S

-

I

-

V

-

G

H

P

A

G

R

I

E

E

V

I

F

Q

F

F

D

S

A

G

E

E

H

H

F

F

F

G

D

D

G

A

F

I

R

E

A

-

N

N

P

F

E

A

F

F

A

T

L

K

S

E

C

A

L

F

E

L

A

T

A

A

H

I

E

E

A

A

G

G

A

A

D

N

V

I

L

I

V

N

L

L

C

P

D

N

T
|
T

N

V

G

E

G

R

S

Y

L

R

P

P

Y

M

Q

V

I

F

A

V

E

N

G

M

V

V

N

K

A

E

V

I

R

K

T

D

R

V

I

V

P

K

N

D

A

K

A

A

V

I

-

I

G

S

I

I

H
|
H

A

T

H
|
H

N

N

D

D

G

L

E

G

L

M

A

A

V

T

A

A

N

T

S

S

L

V

E

E

A

S

I

V

R

Y

H

V

G

G

A

A

V

E

H

Q

V

I

Q

E

G

V

T

A

M

L

N

N

G

G

Y

L

G

G

E

E

R

R

C

A

G

G

N

N

A

T

N

N

L

L

C

-

S

-

I

-

P

-

N

-

L

Y

E

E

L

T

K

A

L

I

G

A

M

L

E

H

S

Q

I

N

G

G

A

E

E

N

-

L

-

N

-

I

N

N

M

F

S

Q

R

R

L

I

T

Y

E

P

V

T

S

A

H

K

Y

R

I

I

S

S

E

E

I

L

A

T

N

G

L

I

R

P

P

I

F

G

M

E

R

K

Q

T

P

P

F

I

V

I

G

G

A

E

S

D

A

I

F

F

A

S

H

H

K

R

G

S

G

G

V

I

H

H

V

-

S

Q

A

T

V

L

R

H

K

Q

D

S

S

K

R

G

T

A

Y

Y

E

R

H

T

I

F

K

S

P

P

T

E

D

F

V

V

G

G

N

R

M

M

Q

D

R

K

V

E

L

T

L

I

S

S

D

-

L

F

A

T

G

N

R

Q

S

S

N

G

L

-

H

H

K

K

A

A

E

I

Q

E

F

F

active site: Q16 (= Q16)
binding (2S)-2-hydroxy-2-(propan-2-yl)butanedioic acid: R12 (= R12), L73 (≠ F73), T176 (= T178), H205 (= H206), H207 (= H208)
binding zinc ion: D13 (= D13), H205 (= H206), H207 (= H208)

4ov4A Isopropylmalate synthase binding with ketoisovalerate (see paper)
28% identity, 64% coverage: 4:346/533 of query aligns to 4:336/379 of 4ov4A

query
sites
4ov4A

I

I

A

H

I

I

Y

Q

D

D

T

V

T

T

L

L

R
|
R

D
|
D

G

G

T

N

Q
|
Q

A

A

E

L

E

K

L

R

N

P

L

W

T

T

T

I

K

D

D

E

K

K

V

I

R

E

I

V

A

F

A

D

K

L

L

L

D

V

E

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

S

S

N

N

P

E

T

T

D

E

K

F

Q

H

F

T

F

C

D

Q

E

V

I

L

A

S

E

K

H

R

T

A

F

P

K

K

N

G

A

K

S

P

I

I

A

A

F

L

G

S

S

-

T

-

F

-

N

-

P

-

K

R

A

A

D

N

P

Q

D

N

S

E

D

I

P

A

I

V

-

T

F

W

Q

E

S

A

L

I

L

Q

T

K

C

A

G

D

A

C

E

P

V

R

F

M

T

H

I

I

F

V

G

Y

K

P

T

V

W

S

D

D

L

F

H

S

A

I

T

K

L

H

A

V

L

L

N

K

I

I

D

S

T

E

E

K

R

E

N

V

I

L

E

Q

I

K

I

I

R

R

Q

N

S

S

V

I

A

S

H

F

L

A

R

R

P

S

-

I

-

V

-

G

H

P

A

G

R

I

E

E

V

I

F

Q

F

F

D

S

A

G

E

E

H

H

F

F

F

G

D

D

G

A

F

I

R

E

A

-

N

N

P

F

E

A

F

F

A

T

L

K

S

E

C

A

L

F

E

L

A

T

A

A

H

I

E

E

A

A

G

G

A

A

D

N

V

I

L

I

V

N

L

L

C
x
P

D

N

T
|
T

N

V

G

E

G

R

S

Y

L

R

P

P

Y

M

Q

V

I

F

A

V

E

N

G

M

V

V

N

K

A

E

V

I

R

K

T

D

R

V

I

V

P

K

N

D

A

K

A

A

V

I

-

I

G

S

I

I

H
|
H

A

T

H
|
H

N

N

D

D

G

L

E

G

L

M

A

A

V

T

A

A

N

T

S

S

L

V

E

E

A

S

I

V

R

Y

H

V

G

G

A

A

V

E

H

Q

V

I

Q

E

G

V

T

A

M

L

N

N

G

G

Y

L

G

G

E

E

R

R

C

A

G

G

N

N

A

T

N

N

L

L

C

-

S

-

I

-

P

-

N

-

L

Y

E

E

L

T

K

A

L

I

G

A

M

L

E

H

S

Q

I

N

G

G

A

E

E

N

-

L

-

N

-

I

N

N

M

F

S

Q

R

R

L

I

T

Y

E

P

V

T

S

A

H

K

Y

R

I

I

S

S

E

E

I

L

A

T

N

G

L

I

R

P

P

I

F

G

M

E

R

K

Q

T

P

P

F

I

V

I

G

G

A

E

S

D

A

I

F

F

A

S

H

H

K

R

G

S

G

G

V

I

H

H

V

Q

S

H

A

Q

V

S

R

K

K

G

D

A

S

Y

R

R

T

T

Y

F

E

-

H

-

I

-

K

S

P

P

T

E

D

F

V

V

G

G

N

R

M

M

Q

D

R

K

V

E

L

T

L

I

S

S

D

-

L

F

A

T

G

N

R

Q

S

S

N

G

L

-

H

H

K

K

A

A

E

I

Q

E

F

F

active site: Q16 (= Q16)
binding 3-methyl-2-oxobutanoic acid: R12 (= R12), P174 (≠ C176), T176 (= T178), H205 (= H206), H207 (= H208)
binding zinc ion: D13 (= D13), H205 (= H206), H207 (= H208)

Q8F3Q1 (R)-citramalate synthase CimA; LiCMS; EC 2.3.3.21 from Leptospira interrogans serogroup Icterohaemorrhagiae serovar Lai (strain 56601) (see 2 papers)
25% identity, 71% coverage: 3:380/533 of query aligns to 7:384/516 of Q8F3Q1

query
sites
Q8F3Q1

R

R

I

L

A

E

I

I

Y

L

D

D

T

V

T

T

L

L

R
|
R

D
|
D

G

G

T

E

Q

Q

A

T

E

R

E

G

L

V

N

S

L

F

T

S

T

T

K

S

D

E

K

K

V

L

R

N

I

I

A

A

A

K

-

F

K

L

L

L

D

Q

E

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

S

V

N

S

P

K

T

G

D

E

K

L

Q

E

F

T

F

V

D

Q

E

K

I

I

A

M

E

E

H

W

T

-

F

-

K

-

N

-

A

A

S

A

I

T

A

E

A

Q

F

L

G

T

S

E

T

R

F

I

N

E

P

I

K
x
L

A

G

D
x
F

P

V

D

D

S

G

D

N

P

K

I

T

F

V

Q

D

S

W

L

I

L

K

T

D

C

S

G

G

A

A

E

K

V

V

F

L

T

N

I

L

F
x
L

G

T

K

K

T

G

W

S

D

L

L

H

H

H

A

L

T

E

L

K

A

Q

L

L

N

G

I

K

D

T

T

P

E

K

R

E

N

F

I

F

E

T

I

D

I

V

R

S

Q

F

S

V

V

I

A

E

H

Y

L

A

R

I

P

K

H

S

A

G

R

L

E

K

V

I

F

N

F

V

D
x
Y

A

L

E
|
E

H

D

F

W

F

S

D

N

G

G

F

F

R

R

A

N

N

S

P

P

E

D

F

Y

A

V

L

K

S

S

C

L

L

V

E

E

A

H

A

L

H

S

E

K

A

E

G

H

A

I

D

E

V

R

L

I

V

F

L

L

C

P

D

D

T
|
T

N

L

G

G

G

V

S

L

L

S

P

P

Y

E

Q

E

I

T

A

F

E

Q

G

G

V

V

N

D

A

S

V

L

R

I

T

Q

R

K

I

Y

P

P

N

D

A

I

A

H

V

F

G

E

I

F

H

H

A

G

H

H

N

N

D

D

G

Y

E

D

L

L

A

S

V

V

A

A

N

N

S

S

L

L

E

Q

A

A

I

I

R

R

H

A

G

G

A

V

V

K

H

G

V

L

Q

H

G

A

T

S

M

I

N

N

G

G

Y

L

G

G

E

E

R

R

C

A

G

G

N

N

A

T

N

P

L

L

C

E

S

A

I

L

I

V

P

T

N

T

L

I

E

H

L

D

K

K

L

S

G

N

M

S

E

K

S

T

I

-

G

-

A

N

E

I

N

N

M

E

S

I

R

A

L

I

T

T

E

E

V

A

S

S

H

R

Y

L

I

V

S

E

E

V

I

F

A

S

N

G

L

K

R

R

P

I

F

S

M

A

R

N

Q

R

P

P

F

I

V

V

G

G

A

E

S

D

A

V

F

F

A

T

H

Q

K

T

G

A

G

G

V

V

H
|
H

V

A

S
x
D

A

G

V

D

R

K

K

K

D

G

S
x
N

R
x
L

T
x
Y

Y

A

E

N

H

P

I

I

K

L

P

P

T

E

D

R

V

F

G

G

N

R

M

K

Q

R

R

S

V

Y

L

A

L

L

S

G

D

K

L

L

A

A

G

G

R

K

S

A

N

S

L

I

L

S

H

E

K

N

A

V

E

K

Q

Q

F

L

G

G

H

M

-

V

-

L

-

S

-

E

-

V

P

V

L

L

E

Q

K

K

G

V

D

L

P

E

R

R

L

V

D

I

Q

E

L

L

V

G

R

D

E

Q

L

N

K

K

L

L

R

V

E

T

S

P

E

E

G

D

F

L

E

P

Y

F

S

I

V

I

A

A

E

D

A

V

S

S

R16 (= R12) mutation R->K,Q: Loss of activity.
RD 16:17 (= RD 12:13) binding pyruvate
D17 (= D13) 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 (≠ K80) 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 (≠ D82) mutation to A: 5-fold increase in Km for acetyl-CoA and 120-fold decrease in kcat.
L104 (≠ F103) mutation to V: 1.8-fold increase in Km for pyruvate and 3.4-fold decrease in kcat.
Y144 (≠ D143) 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 (= E145) mutation E->D,Q: Minor effects on the binding of acetyl-CoA, but causes a strong decrease in kcat.
T179 (= T178) binding pyruvate; mutation to A: 16.4-fold increase in Km for pyruvate and 186-fold decrease in kcat.
H302 (= H303) mutation H->A,N: Loss of activity.
D304 (≠ S305) mutation to A: 5.2-fold increase in Km for acetyl-CoA and 16.6-fold decrease in kcat.
N310 (≠ S311) mutation to A: 2.2-fold increase in Km for acetyl-CoA and 1.7-fold decrease in kcat.
L311 (≠ R312) mutation to A: 8-fold increase in Km for acetyl-CoA and 6-fold decrease in kcat.
Y312 (≠ T313) mutation to A: Loss of activity.

Sites not aligning to the query:

430 Y→L: No change in Km for acetyl-CoA and 2.3-fold decrease in kcat. Severely impairs inhibition by isoleucine.
431 D→A: 1.8-fold decrease in Km for acetyl-CoA and 5-fold decrease in kcat.
451 L→V: 1.5-fold increase in Km for acetyl-CoA and 4.3 decrease in kcat.
454 Y→A: 1.4 decrease in Km for acetyl-CoA and 17-fold decrease in kcat. Still inhibited by isoleucine and weakly inhibited by leucine.
458 I→A: 1.3-fold decrease in Km for acetyl-CoA and 14-fold decrease in kcat. Abolishes inhibition by isoleucine.
464 T→A: 1.8-fold decrease in Km for acetyl-CoA and 4.3-fold decrease in kcat.
468 V→A: No change in Km for acetyl-CoA and 2-fold decrease in kcat. Increases inhibition by isoleucine and leucine becomes an effective inhibitor.
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.

3ivsA Homocitrate synthase lys4 (see paper)
25% identity, 69% coverage: 1:367/533 of query aligns to 9:348/364 of 3ivsA

query
sites
3ivsA

M

V

H

N

R

N

I

F

A

S

I

I

Y

I

D

E

T

S

T

T

L

L

R

R

D
x
E

G

G

T

E

Q
|
Q

A

F

E

A

E

N

L

A

N

F

L

F

T

D

T

T

K

E

D

K

K

K

V

I

R

Q

I

I

A

A

A

K

K

A

L

L

D

D

E

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

S

A

N

S

P

E

T

Q

D

S

K

R

Q

Q

F

D

F

C

D

E

E

A

I

I

A

C

E

K

H

L

T

G

F

L

K

K

N

C

A

K

S

I

I

L

A

T

A

-

F

-

G

-

S

-

T

-

F

-

N

H

P

I

K

R

A

C

D

H

P

M

D

D

S

D

D

A

P

R

I

V

F

A

Q

V

S

E

L

T

L

G

T

V

C

D

G

G

A

V

E

D

V

V

F

-

T

-

I

V

F

I

G

G

K

T

T

T

W

Y

D

I

L

I

-

D

H

S

A

A

T

T

L

E

A

V

L

I

N

N

I

F

D

V

T

K

E

S

R

K

N

G

I

I

E

-

I

-

R

-

Q

-

S

-

V

-

A

-

H

-

L

-

R

-

P

-

H

-

A

-

R

-

E

E

V

V

F

R

F

F

D

S

A

S

E

E

H

-

F

-

D

D

G

S

F

F

R

R

A

S

N

D

P

L

E

V

F

D

A

L

L

L

S

S

C

L

L

Y

E

K

A

A

A

V

H

D

E

K

A

I

G

G

A

V

D

N

V

R

L

V

V

G

L

I

C

A

D

D

T

T

N

V

G

G

G

C

S

A

L

T

P

P

Y

R

Q

Q

I

V

A

Y

E

D

G

L

V

I

N

R

A

T

V

L

R

R

T

G

R

-

I

V

P

V

N

S

A

C

A

D

V

I

G

E

I

C

H
|
H

A

F

H
|
H

N

N

D

D

G

T

E

G

L

M

A

A

V

I

A

A

N

N

S

A

L

Y

E

C

A

A

I

L

R

E

H

A

G

G

A

A

V

T

H

H

V

I

Q

D

G

T

T

S

M

I

N

L

G

G

Y

I

G

G

E

E

R

R

C

N

G

G

N

I

A

T

N

P

L

L

C

G

S

A

I

L

P

A

N

R

L

M

E

Y

L

V

K

T

L

D

G

R

M

E

E

Y

S

I

I

T

G

H

A

K

E

Y

N

K

M

L

S

N

R

Q

L

L

T

R

E

E

V

L

S

E

H

N

Y

L

I

V

S

A

E

D

I

A

A

V

N

E

L

V

R

Q

P

I

F

P

M

F

R

N

Q

N

P

Y

F

I

V

T

G

G

A

M

S

C

A

A

F

F

A

T

H

H

K

K

G

A

G

G

V

I

H

H

V

A

S

K

A

A

V

I

R

L

K

A

D

N

S

P

R

S

T

T

Y

Y

E

E

H

I

I

L

K

K

P

P

T

E

D

D

V

F

G

G

N

M

M

S

Q

R

R

Y

V

V

L

H

L

V

-

G

S

S

D

R

L

L

A

T

G

G

R

W

S

N

N

A

L

I

L

K

H

S

K

R

A

A

E

E

Q

Q

F

L

G

N

H

L

P

H

L

L

E

Q

K

A

G

K

D

E

P

-

R

-

L

L

D

T

Q

V

L

R

V

I

R

K

E

K

L

L

K

A

L

V

R

R

active site: Q24 (= Q16)
binding cobalt (ii) ion: E21 (≠ D13), H188 (= H206), H190 (= H208)

3ivtB Homocitrate synthase lys4 bound to 2-og (see paper)
25% identity, 69% coverage: 1:367/533 of query aligns to 27:375/400 of 3ivtB

query
sites
3ivtB

M

V

H

N

R

N

I

F

A

S

I

I

Y

I

D

E

T

S

T

T

L

L

R
|
R

D
x
E

G

G

T

E

Q
|
Q

A

F

E

A

E

N

L

A

N

F

L

F

T

D

T

T

K

E

D

K

K

K

V

I

R

Q

I

I

A

A

A

K

K

A

L

L

D

D

E

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

S

A

N

S

P

E

T

Q

D

S

K

R

Q

Q

F

D

F

C

D

E

E

A

I

I

A

C

E

K

H

L

T

G

F

L

K

K

N

C

A

K

S

I

I

L

A

T

A
x
H

F

I

G

-

S

-

T

-

F

-

N

-

P

-

K

R

A

C

D

H

P

M

D

D

S

D

D

A

P

R

I

V

F

A

Q

V

S

E

L

T

L

G

T

V

C

D

G

G

A

V

E

D

V

V

F

-

T

-

I

V

F

I

G

G

K

T

T

S

W

Q

D

Y

L

L

H

R

A

K

T

-

L

Y

A

S

L

H

N

G

I

K

D

D

T

M

E

T

R

Y

N

I

I

I

E

D

I

S

I

A

R

T

Q

E

S

V

V

I

A

N

H

F

L

V

R

K

P

S

H

K

A

G

R

I

E

E

V

V

F
x
R

F

F

D
x
S

A

S

E

E

H

-

F

-

D

D

G

S

F

F

R

R

A

S

N

D

P

L

E

V

F

D

A

L

L

L

S

S

C

L

L

Y

E

K

A

A

A

V

H

D

E

K

A

I

G

G

A

V

D

N

V

R

L

V

V

G

L

I

C

A

D

D

T
|
T

N

V

G

G

G

C

S

A

L

T

P

P

Y

R

Q

Q

I

V

A

Y

E

D

G

L

V

I

N

R

A

T

V

L

R

R

T

G

R

-

I

V

P

V

N

S

A

C

A

D

V

I

G

E

I

C

H
|
H

A

F

H
|
H

N

N

D

D

G

T

E

G

L

M

A

A

V

I

A

A

N

N

S

A

L

Y

E

C

A

A

I

L

R

E

H

A

G

G

A

A

V

T

H

H

V

I

Q

D

G

T

T

S

M

I

N

L

G

G

Y

I

G

G

E

E

R

R

C

N

G

G

N

I

A

T

N

P

L

L

C

G

S

A

I

L

P

A

N

R

L

M

E

Y

L

V

K

T

L

D

G

R

M

E

E

Y

S

I

I

T

G

H

A

K

E

Y

N

K

M

L

S

N

R

Q

L

L

T

R

E

E

V

L

S

E

H

N

Y

L

I

V

S

A

E

D

I

A

A

V

N

E

L

V

R

Q

P

I

F

P

M

F

R

N

Q

N

P

Y

F

I

V

T

G

G

A

M

S

C

A

A

F

F

A

T

H

H

K

K

G

A

G

G

V

I

H

H

V

A

S

K

A

A

V

I

R

L

K

A

D

N

S

P

R

S

T

T

Y

Y

E

E

H

I

I

L

K

K

P

P

T

E

D

D

V

F

G

G

N

M

M

S

Q

R

R

Y

V

V

L

H

L

V

-

G

S

S

D

R

L

L

A

T

G

G

R

W

S

N

N

A

L

I

L

K

H

S

K

R

A

A

E

E

Q

Q

F

L

G

N

H

L

P

H

L

L

E

T

K

-

G

-

D

-

P

-

R

-

L

-

D

D

Q

A

L

Q

V

A

R

K

E

E

L

L

K

T

L

V

R

R

active site: Q42 (= Q16)
binding 2-oxoglutaric acid: R38 (= R12), H98 (≠ A72), R158 (≠ F141), S160 (≠ D143), T192 (= T178), H219 (= H206), H221 (= H208)
binding zinc ion: E39 (≠ D13), H219 (= H206), H221 (= H208)

Q9Y823 Homocitrate synthase, mitochondrial; HCS; EC 2.3.3.14 from Schizosaccharomyces pombe (strain 972 / ATCC 24843) (Fission yeast) (see 2 papers)
25% identity, 69% coverage: 1:367/533 of query aligns to 32:380/418 of Q9Y823

query
sites
Q9Y823

M

V

H

N

R

N

I

F

A

S

I

I

Y

I

D

E

T

S

T

T

L

L

R
|
R

D
x
E

G

G

T

E

Q
|
Q

A

F

E

A

E

N

L

A

N

F

L

F

T

D

T

T

K

E

D

K

K

K

V

I

R

Q

I

I

A

A

A

K

K

A

L

L

D

D

E

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

S

A

N

S

P

E

T

Q

D

S

K

R

Q

Q

F

D

F

C

D

E

E

A

I

I

A

C

E

K

H

L

T

G

F

L

K

K

N

C

A

K

S

I

I

L

A

T

A
x
H

F

I

G

-

S

-

T

-

F

-

N

-

P

-

K

R

A

C

D

H

P

M

D

D

S

D

D

A

P

R

I

V

F

A

Q

V

S

E

L

T

L

G

T

V

C

D

G

G

A

V

E
x
D

V

V

F

-

T

-

I

V

F

I

G

G

K

T

T

S

W

Q

D

Y

L

L

H

R

A

K

T

-

L

Y

A

S

L

H

N

G

I

K

D

D

T

M

E

T

R

Y

N

I

I

I

E

D

I

S

I

A

R

T

Q

E

S

V

V

I

A

N

H

F

L

V

R

K

P

S

H

K

A

G

R

I

E

E

V

V

F
x
R

F

F

D
x
S

A

S

E
|
E

H

-

F

-

D

D

G

S

F

F

R

R

A

S

N

D

P

L

E

V

F

D

A

L

L

L

S

S

C

L

L

Y

E

K

A

A

A

V

H

D

E

K

A

I

G

G

A

V

D

N

V

R

L

V

V

G

L

I

C

A

D

D

T
|
T

N

V

G

G

G

C

S

A

L

T

P

P

Y

R

Q

Q

I

V

A

Y

E

D

G

L

V

I

N

R

A

T

V

L

R

R

T

G

R

-

I

V

P

V

N

S

A

C

A

D

V

I

G
x
E

I

C

H
|
H

A

F

H
|
H

N

N

D

D

G

T

E

G

L

M

A

A

V

I

A

A

N

N

S

A

L

Y

E

C

A

A

I

L

R

E

H

A

G

G

A

A

V

T

H

H

V

I

Q

D

G

T

T

S

M

I

N

L

G

G

Y

I

G

G

E

E

R

R

C

N

G

G

N

I

A

T

N

P

L

L

C

G

S

A

I

L

P

A

N

R

L

M

E

Y

L

V

K

T

L

D

G

R

M

E

E

Y

S

I

I

T

G

H

A

K

E

Y

N

K

M

L

S

N

R

Q

L

L

T
x
R

E

E

V

L

S

E

H

N

Y

L

I

V

S

A

E

D

I

A

A

V

N

E

L

V

R

Q

P

I

F

P

M

F

R

N

Q

N

P

Y

F

I

V

T

G

G

A

M

S

C

A

A

F

F

A

T

H

H

K

K

G

A

G

G

V

I

H

H

V

A

S

K

A

A

V

I

R

L

K

A

D

N

S

P

R

S

T

T

Y
|
Y

E

E

H

I

I

L

K

K

P

P

T

E

D

D

V

F

G

G

N

M

M

S

Q

R

R

Y

V

V

L

H

L

V

-

G

S

S

D

R

L

L

A

T

G

G

R

W

S

N

N

A

L

I

L

K

H

S

K

R

A

A

E

E

Q
|
Q

F

L

G

N

H

L

P

H

L

L

E

T

K

-

G

-

D

-

P

-

R

-

L

-

D

D

Q

A

L

Q

V

A

R

K

E

E

L

L

K

T

L

V

R

R

R43 (= R12) binding 2-oxoglutarate; mutation R->A,K,Q: Abolishes the catalytic activity.
E44 (≠ D13) binding 2-oxoglutarate; binding L-lysine; binding Zn(2+)
Q47 (= Q16) mutation to A: Abolishes the catalytic activity.
E74 (= E43) 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 (≠ A72) binding 2-oxoglutarate; mutation to A: Substantially impairs catalytic efficiency.
D123 (≠ E98) binding L-lysine; mutation to N: Does not affect the catalytic activity but impairs L-lysine inhibition.
R163 (≠ F141) 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 (≠ D143) binding 2-oxoglutarate; mutation to A: Results in a moderate decrease in catalytic efficiency.
E167 (= E145) mutation E->A,Q: Abolishes the catalytic activity.
T197 (= T178) 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 (≠ G204) mutation to Q: Does not affect the catalytic activity but impairs L-lysine inhibition.
H224 (= H206) binding 2-oxoglutarate; binding Zn(2+)
H226 (= H208) binding 2-oxoglutarate; binding Zn(2+)
R288 (≠ T270) mutation to K: Does not affect the catalytic activity but impairs L-lysine inhibition.
Y332 (= Y314) mutation to A: Abolishes the catalytic activity.; mutation to F: Results in a decrease in catalytic efficiency.
Q364 (= Q345) mutation to R: Does not affect the catalytic activity but impairs L-lysine inhibition.

3mi3A Homocitrate synthase lys4 bound to lysine (see paper)
25% identity, 69% coverage: 1:367/533 of query aligns to 9:346/370 of 3mi3A

query
sites
3mi3A

M

V

H

N

R

N

I

F

A

S

I

I

Y

I

D

E

T

S

T

T

L

L

R
|
R

D
x
E

G

G

T

E

Q
|
Q

A

F

E

A

E

N

L

A

N

F

L

F

T

D

T

T

K

E

D

K

K

K

V

I

R

Q

I

I

A

A

A

K

K

A

L

L

D

D

E

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

S

A

N

S

P

E

T

Q

D

S

K

R

Q

Q

F

D

F

C

D

E

E

A

I

I

A

C

E

K

H

L

T

G

F

L

K

K

N

C

A

K

S

I

I

L

A

T

A

-

F

-

G

-

S

-

T

-

F

-

N

H

P

I

K

R

A

C

D

H

P

M

D

D

S

D

D

A

P

R

I

V

F

A

Q

V

S

E

L

T

L

G

T

V

C

D

G

G

A

V

E
x
D

V

V

F

V

T

I

I

G

F

T

G

S

K

M

T

T

W

Y

D

I

L

I

-

D

H

S

A

A

T

T

L

E

A

V

L

I

N

N

I

F

D

V

T

K

E

S

R

K

N

G

I

I

E

E

I

-

R

-

Q

-

S

-

V

-

A

-

H

-

L

-

R

-

P

-

H

-

A

-

R

-

E

-

V

V

F

R

F

F

D

S

A

S

E

E

H

-

F

-

D

D

G

S

F

F

R

R

A

S

N

D

P

L

E

V

F

D

A

L

L

L

S

S

C

L

L

Y

E

K

A

A

A

V

H

D

E

K

A

I

G

G

A

V

D

N

V

R

L

V

V

G

L

I

C

A

D

D

T
|
T

N

V

G

G

G

C

S

A

L

T

P

P

Y

R

Q

Q

I

V

A

Y

E

D

G

L

V

I

N

R

A

T

V

L

R

R

T

G

R

-

I

V

P

V

N

S

A

C

A

D

V

I

G

E

I

C

H
|
H

A

F

H
|
H

N

N

D

D

G

T

E

G

L

M

A

A

V

I

A

A

N

N

S

A

L

Y

E

C

A

A

I

L

R

E

H

A

G

G

A

A

V

T

H

H

V

I

Q

D

G

T

T

S

M

I

N

L

G

G

Y

I

G

G

E

E

R

R

C

N

G

G

N

I

A

T

N

P

L

L

C

G

S

A

I

L

P

A

N

R

L

M

E

Y

L

V

K

T

L

D

G

R

M

E

E

Y

S

I

I

T

G

H

A

K

E

Y

N

K

M

L

S

N

R

Q

L

L

T

R

E

E

V

L

S

E

H

N

Y

L

I

V

S

A

E

D

I

A

A

V

N

E

L

V

R

Q

P

I

F

P

M

F

R

N

Q

N

P

Y

F

I

V

T

G

G

A

M

S

C

A

A

F

F

A

T

H

H

K

K

G

A

G

G

V

I

H

H

V

A

S

K

A

A

V

I

R

L

K

A

D

N

S

P

R

S

T

T

Y

Y

E

E

H

I

I

L

K

K

P

P

T

E

D

D

V

F

G

G

N

M

M

S

Q

R

R

Y

V

V

L

H

L

V

-

G

S

S

D

R

L

L

A

T

G

G

R

W

S

N

N

A

L

I

L

K

H

S

K

R

A

A

E

E

Q

Q

F

L

G

N

H

L

P

H

L

L

E

T

K

-

G

-

D

-

P

-

R

-

L

-

D

D

Q

A

L

Q

V

A

R

K

E

E

L

L

K

T

L

V

R

R

active site: Q24 (= Q16)
binding lysine: R20 (= R12), D100 (≠ E98), T163 (= T178), H190 (= H206), H192 (= H208)
binding zinc ion: E21 (≠ D13), H190 (= H206), H192 (= H208)

3bliA Crystal structure of the catalytic domain of licms in complexed with pyruvate and acetyl-coa (see paper)
26% identity, 57% coverage: 3:306/533 of query aligns to 1:299/311 of 3bliA

query
sites
3bliA

R

R

I

L

A

E

I

I

Y

L

D

D

T

V

T

T

L

L

R
|
R

D
|
D

G

G

T

E

Q
|
Q

A

T

E

R

E

G

L

V

N

S

L

F

T

S

T

T

K

S

D

E

K

K

V

L

R

N

I

I

A

A

A

K

-

F

K

L

L

L

D

Q

E

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

S
x
V

N

S

P

K

T

G

D

E

K

L

Q

E

F

T

F

V

D

Q

E

K

I

I

A

M

E

E

H

W

T

-

F

-

K

-

N

-

A

A

S

A

I

T

A

E

A

Q

F

L

G

T

S

E

T

R

F

I

N

E

P

I

K

L

A

G

D

F

P

V

D

D

S

G

D

N

P

K

I

T

F

V

Q

D

S

W

L

I

L

K

T

D

C

S

G

G

A

A

E

K

V

V

F

L

T

N

I

L

F

L

G

T

K

K

T

G

W

S

D

L

L

H

H

H

A

L

T

E

L

K

A

Q

L

L

N

G

I

K

D

T

T

P

E

K

R

E

N

F

I

F

E

T

I

D

I

V

R

S

Q

F

S

V

V

I

A

E

H

Y

L

A

R

I

P

K

H

S

A

G

R

L

E

K

V

I

F

N

F

V

D
x
Y

A

L

E
|
E

H

D

F

W

F

S

D

N

G

G

F

F

R

R

A

N

N

S

P

P

E

D

F

Y

A

V

L

K

S

S

C

L

L

V

E

E

A

H

A

L

H

S

E

K

A

E

G

H

A

I

D

E

V

R

L

I

V

F

L

L

C
x
P

D

D

T
|
T

N

L

G

G

G

V

S

L

L

S

P

P

Y

E

Q

E

I

T

A

F

E

Q

G

G

V

V

N

D

A

S

V

L

R

I

T

Q

R

K

I

Y

P

P

N

D

A

I

A

H

V

F

G

E

I

F

H
|
H

A

G

H
|
H

N

N

D

D

G

Y

E

D

L

L

A

S

V

V

A

A

N

N

S

S

L

L

E

Q

A

A

I

I

R

R

H

A

G

G

A

V

V

K

H

G

V

L

Q

H

G

A

T

S

M

I

N

N

G

G

Y

L

G

G

E

E

R

R

C

A

G

G

N

N

A

T

N

P

L

L

C

E

S

A

I

L

I

V

P

T

N

T

L

I

E

H

L

D

K

K

L

-

G

-

M

S

E

N

S

S

I

K

G

T

A

N

E

I

N

N

M

E

S

I

R

A

L

I

T

T

E

E

V

A

S

S

H

R

Y

L

I

V

S

E

E

V

I

F

A

S

N

G

L

K

R

R

P

I

F

S

M

A

R

N

Q

R

P

P

F

I

V

V

G

G

A

E

S

D

A

V

F

F

A

T

H

Q

K

T

G

A

G

G

V

V

H

N

V

L

S

Y

A

A

active site: Q14 (= Q16)
binding acetyl coenzyme *a: Q14 (= Q16), R47 (≠ G48), V48 (≠ S49), E140 (= E145)
binding pyruvic acid: R10 (= R12), Y138 (≠ D143), P171 (≠ C176), T173 (= T178)
binding zinc ion: D11 (= D13), H201 (= H206), H203 (= H208)

Q53WI0 4-hydroxy-2-oxovalerate aldolase; HOA; 4-hydroxy-2-keto-pentanoic acid aldolase; 4-hydroxy-2-oxohexanoate aldolase; 4-hydroxy-2-oxopentanoate aldolase; EC 4.1.3.39; EC 4.1.3.43 from Thermus thermophilus (strain ATCC 27634 / DSM 579 / HB8) (see paper)
27% identity, 53% coverage: 6:285/533 of query aligns to 13:278/347 of Q53WI0

query
sites
Q53WI0

I

V

Y

V

D

D

T

T

L

L

R

R

D

D

G

G

T

S

Q

H

A

A

E

H

E

R

L

H

N

Q

L

Y

T

T

T

V

K

E

D

E

K

A

V

R

R

A

I

I

A

A

A

Q

K

A

L

L

D

D

E

E

L

A

G

G

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V

H

Y

Y

A

I

I

E

E

-

V

-

S

-

H

-

G

-

D

-

G

-

L

G

G

W

S

P

S

-

L

-

Q

-

Y

G

G

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F

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S

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R

T

T

D

D

K

E

Q

M

F

E

F

L

D

I

E

R

I

A

A

V

E

R

H

E

T

T

F

V

K

R

N

R

A

A

S

K

I

V

A

A

F

L

G

-

S

-

T

-

F

L

N

L

P

P

K

G

A

I

D

G

P

T

D

R

S

K

D

E

P

-

I

-

F

L

Q

K

S

E

L

A

L

V

T

E

C

A

G

G

A

I

E

Q

V

M

F

V

T

R

I

I

F

A

G

T

K

Q

T

C

W

T

D

E

L

A

H

D

A

I

T

S

L

E

A

Q

-

H

L

F

N

G

I

M

D

A

T

K

E

E

R

M

N

G

I

L

E

E

I

A

I

V

R

G

-

F

Q

L

S

M

V

M

A

S

H

H

L

M

R

R

P

P

H

-

A

-

R

-

E

-

V

-

F

-

D

-

A

-

E

-

H

-

F

-

D

-

G

-

F

-

R

-

A

-

N

-

P

P

E

E

F

F

A

L

L

A

S

E

C

Q

L

A

E

R

A

L

A

M

H

E

E

G

A

Y

G

G

A

A

D

D

V

V

L

V

V

Y

L

I

C

V

D

D

T

S

N

A

G

G

G

A

S

M

L

L

P

P

Y

E

Q

D

I

A

A

Y

E

A

G

R

V

V

N

K

A

A

V

L

R

K

T

E

R

A

I

L

P

S

N

R

A

A

A

K

V

V

G

G

I

F

H

H

A

A

H

H

N

N

D

N

G

L

E

G

L

L

A

A

V

I

A

G

N

N

S

T

L

L

E

A

A

A

I

L

R

A

H

A

G

G

A

A

V

D

H

W

V

V

Q

D

G

A

T

T

M

L

N

R

G

G

Y

Y

G

G

E

A

R

G

C

A

G

G

N

N

A

A

N

P

L

L

C

E

S

V

I

L

I

A

P

A

N

V

L

L

E

D

L

-

K

K

L

A

G

G

M

L

E

N

S

P

I

-

G

G

A

L

E

D

N

V

M

F

S

K

R

L

L

L

T

D

E

A

V

A

S

E

H

Y

Y

V

I

M

S

G

E

P

I

I

A

L

N

H

L

F

R

Q

P

P

F

Y

Sites not aligning to the query:

324 A→G: Increases the channeling efficiency of propanaldehyde from 57% to 94%.

P35914 Hydroxymethylglutaryl-CoA lyase, mitochondrial; HL; HMG-CoA lyase; 3-hydroxy-3-methylglutarate-CoA lyase; EC 4.1.3.4 from Homo sapiens (Human) (see 11 papers)
24% identity, 53% coverage: 2:281/533 of query aligns to 31:311/325 of P35914

query
sites
P35914

H

K

R

R

I

V

A

K

I

I

Y

V

D
x
E

T

V

T

G

L

P

R
|
R

D
|
D

G

G

T

L

Q

Q

A

N

E

E

E
x
K

L

N

N

I

L

V

T

S

T

T

K

P

D

V

K

K

V

I

R

K

I

L

A

I

A

D

K

M

L

L

D

S

E

E

L

A

G

G

V

L

H

S

Y

V

I

I

E
|
E

G

T

G

-

W

-

P

-

G

-

S

T

N

S

P

F

T

V

D

S

K

P

Q

K

F

W

F

V

D

P

E

Q

I

M

A

G

E

D

H

H

T

T

F

E

K

V

N

L

A

K

S

G

I

I

A

Q

A

K

F

F

G

P

S

G

T

I

F

N

N

Y

P

P

K

V

A

L

D

T

P

P

D

N

S

L

D

K

P

G

I

-

F

F

Q

E

S

A

L

A

L

V

T

A

C

A

G

G

A

A

E

K

V

E

F

V

T

V

I

I

F

F

G

G

K

A

T

A

W

S

D

E

L

L

H

F

A

T

T

K

L

K

A

N

L

I

N

N

I

C

D
x
S

T

I

E

E

R

E

N

S

I

F

E

Q

-

R

-

F

-

D

I

A

I

I

R

L

Q

K

S

A

V

A

A

Q

H

S

L

A

R

N

P

I

H

S

A

V

R

R

E

G

V

Y

F

V

F

S

D

C

A

A

E

L

H

G

F
x
C

F

P

D

Y

G

E

F

G

R

K

A

I

N

S

P

P

E

A

F

K

A

V

L

A

S

E

C

V

L

T

E

K

A

K

A
x
F

H

Y

E

S

A

M

G

G

A

C

D

Y

V

E

L
x
I

V

S

L

L

C
x
G

D
|
D

T

T

N

I

G

G

G

V

S

G

L

T

P

P

Y

G

Q

I

I

M

A

K

E

D

G

M

V

L

N

S

A

A

V

V

R

M

T

Q

R

E

I

V

P

P

N

L

A

A

V

L

G

A

I

V

H
|
H

A

C

H

H

N

D

D

T

G

Y

E

G

L

Q

A

A

V

L

A

A

N

N

S

T

L

L

E

M

A

A

I

L

R

Q

H

M

G

G

A

V

V

S

H

V

V

V

Q

D

G

S

T

S

M

V

N

A

G

G

Y

L

G

G

E

-

R

G

C

C

G

P

N

Y

A

A

N

Q

L

G

C

A

S

S

I

-

P

G

N

N

L

L

-

A

-

T

-
x
E

E
x
D

L

L

K

V

L

Y

G

M

M

L

E

E

S

G

I

L

G

G

-

I

-

H

-

T

A

G

E

V

N

N

M

L

S

Q

R

K

L

L

T

L

E

E

V

A

S

G

H

N

Y

F

I

I

S

C

E

Q

I

A

A

L

N

N

E37 (≠ D8) to K: in HMGCLD; activity lower than 5% respect to the wild-type; mutation to D: Normal activity.
R41 (= R12) to Q: in HMGCLD; loss of activity and of proton exchange; dbSNP:rs121964997; mutation to M: Reduced activity, and loss of proton exchange.
D42 (= D13) to E: in HMGCLD; reduced activity; to G: in HMGCLD; loss of activity; dbSNP:rs1467902610; to H: in HMGCLD; loss of activity; mutation D->A,N: Loss of activity, and reduced proton exchange rate.
K48 (≠ E19) to N: in HMGCLD; abolishes almost all enzymatic activity
E72 (= E43) mutation to A: Loss of activity, and reduced affinity for metal cofactor and substrate.
S142 (≠ D118) to F: in HMGCLD; activity lower than 5% respect to the wild-type
C174 (≠ F147) to Y: in HMGCLD; activity lower than 5% respect to the wild-type; dbSNP:rs765475941
F192 (≠ A165) to S: in HMGCLD; activity lower than 5% respect to the wild-type
I200 (≠ L173) to F: in HMGCLD; activity lower than 5% respect to the wild-type
G203 (≠ C176) to E: in HMGCLD; complete loss of activity; dbSNP:rs1553131940
D204 (= D177) mutation to A: Reduced activity, and reduced affinity for metal cofactor and substrate.
H233 (= H206) to R: in HMGCLD; loss of activity; dbSNP:rs727503963; mutation to A: Loss of activity, and reduced proton exchange rate.
E279 (vs. gap) mutation to A: Reduced thermal stability, but normal activity.
D280 (≠ E253) mutation to A: Normal activity.

Sites not aligning to the query:

323 modified: Interchain; C→S: Abolishes interchain homodimerization. Exhibits no DTT stimulated activity.

Query Sequence

>WP_018123594.1 NCBI__GCF_000375485.1:WP_018123594.1
MHRIAIYDTTLRDGTQAEELNLTTKDKVRIAAKLDELGVHYIEGGWPGSNPTDKQFFDEI
AEHTFKNASIAAFGSTFNPKADPDSDPIFQSLLTCGAEVFTIFGKTWDLHATLALNIDTE
RNIEIIRQSVAHLRPHAREVFFDAEHFFDGFRANPEFALSCLEAAHEAGADVLVLCDTNG
GSLPYQIAEGVNAVRTRIPNAAVGIHAHNDGELAVANSLEAIRHGAVHVQGTMNGYGERC
GNANLCSIIPNLELKLGMESIGAENMSRLTEVSHYISEIANLRPFMRQPFVGASAFAHKG
GVHVSAVRKDSRTYEHIKPTDVGNMQRVLLSDLAGRSNLLHKAEQFGHPLEKGDPRLDQL
VRELKLRESEGFEYSVAEASFELMFHKIVSGRHFNYFKFRNFFVVDAKREEDAEPFSEAT
VMVHVGDQEEHTAATGMGPVNALDRALRKALERFYPSLADVRLLDFKVRVLSGAVRDTGG
TASFVRVLVESGDSHERWTTVGVSHNIIEASWQAVVDSYNYKLFREDMRKIGK

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