SitesBLAST

SitesBLAST – Find functional sites

SitesBLAST

Comparing WP_027177793.1 NCBI__GCF_000429985.1:WP_027177793.1 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)

Q9FG67 Methylthioalkylmalate synthase 1, chloroplastic; 2-isopropylmalate synthase 3; EC 2.3.3.17 from Arabidopsis thaliana (Mouse-ear cress) (see paper)
31% identity, 95% coverage: 2:351/368 of query aligns to 87:464/506 of Q9FG67

query
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Q9FG67

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S102 (≠ Y17) mutation to F: In gsm1-1; loss of conversion of C3 to C4 glucosinolates.
A290 (= A187) 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)
31% identity, 95% coverage: 2:351/368 of query aligns to 20:397/409 of 6e1jA

query
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6e1jA

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binding coenzyme a: Q30 (= Q12), F60 (≠ W42), S63 (vs. gap), I95 (≠ W67), R97 (≠ P69), F121 (≠ G89), K132 (≠ R100), L133 (= L101), S322 (= S280), G323 (= G281), I324 (≠ L282), D327 (≠ H285), K331 (= K289), L359 (≠ K313), R362 (≠ K316), H363 (≠ A317)
binding 4-(methylsulfanyl)-2-oxobutanoic acid: P192 (≠ S160), T194 (≠ S162), H225 (= H189), H227 (= H191)
binding manganese (ii) ion: D27 (≠ E9), V82 (≠ T62), E84 (vs. gap), H225 (= H189), H227 (= H191)

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)
29% identity, 95% coverage: 2:351/368 of query aligns to 87:464/503 of Q9FN52

query
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Q9FN52

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G263 (= G164) mutation to E: In gsm2-1; loss of activity and lack of C6, C7 and C8 aliphatic 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, 89% coverage: 2:329/368 of query aligns to 24:356/399 of 6ktqA

query
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6ktqA

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binding 2-oxoglutaric acid: R30 (= R8), R154 (≠ S128), T156 (≠ G130), E158 (= E132), S184 (≠ R158), T188 (≠ S162), H216 (= H189), H218 (= H191)
binding coenzyme a: V67 (≠ I43), R96 (≠ P69), A97 (≠ C70), F116 (≠ G89), H128 (≠ L101), E158 (= E132)
binding zinc ion: E31 (= E9), H216 (= H189), H218 (= H191)

3ivtB Homocitrate synthase lys4 bound to 2-og (see paper)
29% identity, 94% coverage: 2:346/368 of query aligns to 32:380/400 of 3ivtB

query
sites
3ivtB

L

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A

active site: Q42 (= Q12)
binding 2-oxoglutaric acid: R38 (= R8), H98 (≠ W67), R158 (≠ S128), S160 (≠ G130), T192 (≠ S162), H219 (= H189), H221 (= H191)
binding zinc ion: E39 (= E9), H219 (= H189), H221 (= H191)

Q9Y823 Homocitrate synthase, mitochondrial; HCS; EC 2.3.3.14 from Schizosaccharomyces pombe (strain 972 / ATCC 24843) (Fission yeast) (see 2 papers)
29% identity, 94% coverage: 2:346/368 of query aligns to 37:385/418 of Q9Y823

query
sites
Q9Y823

L

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x
R

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x
Y

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V

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x
Q

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A

R43 (= R8) binding 2-oxoglutarate; mutation R->A,K,Q: Abolishes the catalytic activity.
E44 (= E9) binding 2-oxoglutarate; binding L-lysine; binding Zn(2+)
Q47 (= Q12) mutation to A: Abolishes the catalytic activity.
E74 (= E39) 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 (≠ W67) binding 2-oxoglutarate; mutation to A: Substantially impairs catalytic efficiency.
D123 (≠ N87) binding L-lysine; mutation to N: Does not affect the catalytic activity but impairs L-lysine inhibition.
R163 (≠ S128) 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 (≠ G130) binding 2-oxoglutarate; mutation to A: Results in a moderate decrease in catalytic efficiency.
E167 (= E132) mutation E->A,Q: Abolishes the catalytic activity.
T197 (≠ S162) 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 (≠ A187) mutation to Q: Does not affect the catalytic activity but impairs L-lysine inhibition.
H224 (= H189) binding 2-oxoglutarate; binding Zn(2+)
H226 (= H191) binding 2-oxoglutarate; binding Zn(2+)
R288 (≠ K250) mutation to K: Does not affect the catalytic activity but impairs L-lysine inhibition.
Y332 (≠ F294) mutation to A: Abolishes the catalytic activity.; mutation to F: Results in a decrease in catalytic efficiency.
Q364 (≠ D325) mutation to R: Does not affect the catalytic activity but impairs L-lysine inhibition.

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)
30% identity, 89% coverage: 1:329/368 of query aligns to 8:349/517 of Q9JZG1

query
sites
Q9JZG1

M

I

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E

V

C

S

T

V

V

L

N

G

G

I

L

G

G

E

E

R

R

S

A

G

G

I
x
N

A

A

A

S

T

V

E

E

L

I

A

V

A

M

Y

A

L

L

A

K

L

V

R

R

C

H

G

D

-

L

-

F

-

G

-

L

K

E

K

T

R

G

Y

I

S

D

T

T

Q

T

K

Q

I

I

K

V

A

P

L

S

C

S

S

K

M

L

V

V

A

S

L

T

E

I

A

T

G

G

V

Y

V

P

V

V

P

Q

R

P

T

N

K

K

A

A

V

I

V

V

G

G

E

A

D

N

I

A

F

F

A

S

C

H

E

E

S

S

G

G

L

I

H

H

T

Q

H

D

A

G

L

V

S

L

K

K

S

H

P

R

E

E

L

T

F

Y

E

E

P

I

Y

M

Q

S

P

A

E

E

S

S

V

V

G

G

-

W

I

A

S

T

R

N

K

R

L

L

A

S

V

L

G

G

G

K

K

L

S

S

G

G

K

R

A

N

A

A

V

F

K

K

S

T

A

K

L

L

K

A

D

D

C

L

G

G

V

I

E

E

D16 (≠ E9) binding Mn(2+)
H204 (= H189) binding Mn(2+)
H206 (= H191) binding Mn(2+)
N240 (≠ I225) binding Mn(2+)

Sites not aligning to the query:

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

3mi3A Homocitrate synthase lys4 bound to lysine (see paper)
29% identity, 94% coverage: 2:346/368 of query aligns to 14:351/370 of 3mi3A

query
sites
3mi3A

L

I

I

I

D

E

T

S

T

T

L

L

R
|
R

E
|
E

G

G

A

E

Q
|
Q

L

F

F

A

G

N

A

A

Y

F

F

F

N

D

L

T

S

E

T

K

R

K

K

I

K

Q

I

I

A

A

A

K

G

A

L

L

A

D

E

N

V

F

G

G

I

V

D

D

E

Y

I

I

E

E

L

L

-

T

G

S

W

P

I

V

G

A

Q

S

D

E

N

Q

L

S

G

R

T

Q

L

D

A

C

E

E

Y

A

I

I

K

C

D

K

I

L

S

G

K

L

D

K

T

C

Y

K

L

I

S

L

V

T

W

H

T

I

P

R

C

C

R

H

E

M

A

D

D

D

I

A

M

R

K

V

A

A

S

V

K

E

L

T

P

G

I

V

D

D

R

G

V

V

N
x
D

I

V

G

V

V

I

P

G

V

T

S

S

D

M

L

T

H

Y

I

I

E

-

R

-

L

-

G

-

L

-

D

-

R

-

N

-

G

-

L

-

L

I

H

D

R

S

L

A

S

T

S

E

A

V

I

I

R

N

T

F

A

V

K

K

A

S

F

K

G

G

I

I

E

E

Y

-

V

V

S

R

V

F

G

S

M

S

E

E

D

D

V

S

S

F

R

R

A

S

D

D

P

L

D

V

F

D

A

L

L

L

T

S

V

L

A

Y

A

K

H

A

A

V

K

D

N

K

C

I

G

G

A

V

S

N

R

R

I

V

R

G

L

I

S

A

D

D

S
x
T

L

V

G

G

Q

C

L

A

T

T

P

P

K

R

S

Q

M

V

E

Y

K

D

L

L

I

I

E

R

T

T

F

L

R

R

N

G

H

V

V

V

K

S

I

C

D

D

T

I

A

E

V

C

H
|
H

C

F

H
|
H

D

N

D

D

F

T

G

G

M

M

A

A

T

I

A

A

N

N

A

A

V

Y

T

C

A

A

L

L

E

E

C

A

G

G

A

A

D

T

Y

H

A

I

D

D

V

T

S

S

V

I

L

L

G

G

I

I

G

G

E

E

R

R

S

N

G

G

I

I

A

T

A

P

T

L

E

G

E

A

L

L

A

L

A

A

Y

R

L

M

A

Y

L

V

R

T

C

D

G

R

K

E

-

Y

-

I

-

T

K

H

R

K

Y

Y

S

K

T

L

Q

N

K

Q

I

L

K

R

A

E

L

L

C

E

S

N

M

L

V

V

A

A

L

D

E

A

A

V

G

E

V

V

V

Q

V

I

P

P

R

F

T

N

K

N

A

Y

V

I

V

T

G

G

E

M

D

C

I

A

F

F

A

T

C

H

E

K

S

A

G

G

L

I

H

H

T

A

H

K

A

A

L

I

S

L

K

A

S

N

P

P

E

S

L

T

F

Y

E

E

P

I

Y

L

Q

K

P

P

E

E

S

D

V

F

G

G

I

M

S

S

R

R

K

Y

L

V

A

H

V

V

G

G

G

S

K

R

-

L

S

T

G

G

K

W

A

N

A

A

V

I

K

K

S

S

A

R

L

A

K

E

D

Q

C

L

G

N

V

L

E

H

N

L

D

T

P

D

K

A

D

Q

I

A

T

K

A

E

L

L

T

T

M

V

A

R

V

I

R

K

Q

K

L

L

S

A

active site: Q24 (= Q12)
binding lysine: R20 (= R8), D100 (≠ N87), T163 (≠ S162), H190 (= H189), H192 (= H191)
binding zinc ion: E21 (= E9), H190 (= H189), H192 (= H191)

3ivsA Homocitrate synthase lys4 (see paper)
29% identity, 94% coverage: 2:346/368 of query aligns to 14:351/364 of 3ivsA

query
sites
3ivsA

L

I

I

I

D

E

T

S

T

T

L

L

R

R

E
|
E

G

G

A

E

Q
|
Q

L

F

F

A

G

N

A

A

Y

F

F

F

N

D

L

T

S

E

T

K

R

K

K

I

K

Q

I

I

A

A

A

K

G

A

L

L

A

D

E

N

V

F

G

G

I

V

D

D

E

Y

I

I

E

E

L

L

-

T

G

S

W

P

I

V

G

A

Q

S

D

E

N

Q

L

S

G

R

T

Q

L

D

A

C

E

E

Y

A

I

I

K

C

D

K

I

L

S

G

K

L

D

K

T

C

Y

K

L

I

S

L

V

T

W

H

T

I

P

R

C

C

R

H

E

M

A

D

D

D

I

A

M

R

K

V

A

A

S

V

K

E

L

T

P

G

I

V

D

D

R

G

V

V

N

D

I

V

G

V

V

I

P

G

V

T

S

T

D

-

L

-

H

-

I

-

E

-

R

-

L

-

G

-

L

-

D

-

R

-

N

-

G

Y

L

I

H

D

R

S

L

A

S

T

S

E

A

V

I

I

R

N

T

F

A

V

K

K

A

S

F

K

G

G

I

I

E

E

Y

-

V

V

S

R

V

F

G

S

M

S

E

E

D

D

V

S

S

F

R

R

A

S

D

D

P

L

D

V

F

D

A

L

L

L

T

S

V

L

A

Y

A

K

H

A

A

V

K

D

N

K

C

I

G

G

A

V

S

N

R

R

I

V

R

G

L

I

S

A

D

D

S

T

L

V

G

G

Q

C

L

A

T

T

P

P

K

R

S

Q

M

V

E

Y

K

D

L

L

I

I

E

R

T

T

F

L

R

R

N

G

H

V

V

V

K

S

I

C

D

D

T

I

A

E

V

C

H
|
H

C

F

H
|
H

D

N

D

D

F

T

G

G

M

M

A

A

T

I

A

A

N

N

A

A

V

Y

T

C

A

A

L

L

E

E

C

A

G

G

A

A

D

T

Y

H

A

I

D

D

V

T

S

S

V

I

L

L

G

G

I

I

G

G

E

E

R

R

S

N

G

G

I

I

A

T

A

P

T

L

E

G

E

A

L

L

A

L

A

A

Y

R

L

M

A

Y

L

V

-

T

-

D

-

R

R

E

C

Y

G

I

K

T

K

H

R

K

Y

Y

S

K

T

L

Q

N

K

Q

I

L

K

R

A

E

L

L

C

E

S

N

M

L

V

V

A

A

L

D

E

A

A

V

G

E

V

V

V

Q

V

I

P

P

R

F

T

N

K

N

A

Y

V

I

V

T

G

G

E

M

D

C

I

A

F

F

A

T

C

H

E

K

S

A

G

G

L

I

H

H

T

A

H

K

A

A

L

I

S

L

K

A

S

N

P

P

E

S

L

T

F

Y

E

E

P

I

Y

L

Q

K

P

P

E

E

S

D

V

F

G

G

I

M

S

S

R

R

K

Y

L

V

A

H

V

V

G

G

G

S

K

R

-

L

S

T

G

G

K

W

A

N

A

A

V

I

K

K

S

S

A

R

L

A

K

E

D

Q

C

L

G

N

V

L

E

H

N

L

D

Q

P

A

K

K

D

E

I

L

T

T

A

V

L

R

T

I

-

K

M

L

A

A

V

V

R

R

Q

T

L

L

S

A

active site: Q24 (= Q12)
binding cobalt (ii) ion: E21 (= E9), H188 (= H189), H190 (= H191)

O87198 Homocitrate synthase; HCS; EC 2.3.3.14 from Thermus thermophilus (strain ATCC BAA-163 / DSM 7039 / HB27) (see paper)
29% identity, 94% coverage: 2:348/368 of query aligns to 6:358/376 of O87198

query
sites
O87198

L

I

I

I

D

D

T

S

T

T

L

L

R
|
R

E
|
E

G

G

A

E

Q

Q

L

F

F

E

G

K

A

A

Y

N

F

F

N

S

L

T

S

Q

T

D

R

K

K

V

K

E

I

I

A

A

A

K

G

A

L

L

A

D

E

E

V

F

G

G

I

I

D

E

E

Y

I

I

E

E

L

V

G

T

W

T

-

P

I

V

G

A

Q

S

D

P

N

Q

L

S

G

R

T

K

L

D

A

A

E

E

Y

V

I

L

K

A

D

S

I

L

S

G

K

L

D

K

T

A

Y

K

L

V

S

V

V

T

W
x
H

T

I

P

Q

C

C

R

R

E

-

A

-

D

-

I

-

M

L

K

D

A

A

S

A

K

K

L

V

P

A

I

V

D

E

R

-

V

-

N

-

I

T

G

G

V

V

P

Q

V

G

S

I

D
|
D

L

L

-

L

-

F

-

G

-

T

-

S

-

K

H

Y

I

L

E

R

E

A

R

A

L

H

G

G

L

R

D

D

R

I

N

P

G

R

L

I

H

E

R

E

L

A

S

K

S

E

A

V

I

I

R

A

T

Y

A

I

K

R

-

E

-

A

A

A

F

P

G

H

I

V

E

E

Y

-

V

V

S
x
R

V

F

G
x
S

M

A

E

E

D

D

V

T

S

F

R

R

A

S

D

E

P

E

D

Q

F

D

A

L

L

L

T

A

V

V

A

Y

A

-

H

E

A

A

K

V

N

A

C

P

G

Y

A

V

S

D

R

R

I

V

R

G

L

L

S

A

D

D

S
x
T

L

V

G

G

Q

V

L

A

T

T

P

P

K

R

S

Q

M

V

E

Y

K

A

L

L

I

V

E

R

T

E

F

V

R

R

N

R

H

V

V

V

-

G

-

P

K

R

I

V

D

D

T

I

A

E

V

F

H
|
H

C

G

H
|
H

D

N

D

D

F

T

G

G

M

C

A

A

T

I

A

A

N

N

A

A

V

Y

T

E

A

A

L

I

E

E

C

A

G

G

A

A

D

T

Y

H

A

V

D

D

V

T

S

T

V

I

L

L

G

G

I

I

G

G

E

E

R

R

S

N

G

G

I

I

A

T

A

P

T

-

E

-

L

L

A

G

Y

F

L

L

A

A

L

R

R

M

C

Y

G

T

-

L

-

Q

-

P

-

E

-

Y

-

V

K

R

R

K

Y

Y

S

K

T

L

Q

E

K

M

I

L

K

P

A

E

L

L

C

D

S

R

M

M

V

V

A

A

L

R

E

M

A

V

G

G

V

V

V

E

V

I

P

P

R

F

T

N

K

N

A

Y

V

I

V

T

G

G

E

E

D

T

I

A

F

F

A

S

C

H

E

K

S

A

G

G

L

M

H

H

T

L

H

K

A

A

L

I

S

Y

K

I

S

N

P

P

E

E

L

A

F

Y

E

E

P

P

Y

Y

Q

P

P

P

E

E

S

V

V

F

G

G

I

V

S

K

R

R

K

K

L

L

A

I

V

I

G

A

G

S

K

R

-

L

S

T

G

G

K

R

A

H

A

A

V

I

K

K

S

A

A

R

L

A

K

E

D

E

C

L

G

G

V

L

E

H

N

Y

D

G

P

E

K

E

D

E

I

L

T

H

A

R

L

V

T

T

M

Q

A

H

V

I

R

K

Q

A

L

L

S

A

S

D

R

R

R12 (= R8) binding 2-oxoglutarate
E13 (= E9) binding Mg(2+)
H72 (≠ W67) 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 (= D94) binding L-lysine
R133 (≠ S128) binding 2-oxoglutarate
S135 (≠ G130) binding L-lysine
T166 (≠ S162) binding 2-oxoglutarate; binding L-lysine
H195 (= H189) binding Mg(2+)
H197 (= H191) binding Mg(2+)

2zyfA Crystal structure of homocitrate synthase from thermus thermophilus complexed with magnesuim ion and alpha-ketoglutarate (see paper)
31% identity, 84% coverage: 2:310/368 of query aligns to 6:313/314 of 2zyfA

query
sites
2zyfA

L

I

I

I

D

D

T

S

T

T

L

L

R
|
R

E
|
E

G

G

A

E

Q
|
Q

L

F

F

E

G

K

A

A

Y

N

F

F

N

S

L

T

S

Q

T

D

R

K

K

V

K

E

I

I

A

A

A

K

G

A

L

L

A

D

E

E

V

F

G

G

I

I

D

E

E

Y

I

I

E

E

L

V

G

T

W

T

-

P

I

V

G

A

Q

S

D

P

N

Q

L

S

G

R

T

K

L

D

A

A

E

E

Y

V

I

L

K

A

D

S

I

L

S

G

K

L

D

K

T

A

Y

K

L

V

S

V

V

T

W
x
H

T

I

P

Q

C

C

R

R

E

-

A

-

D

-

I

-

M

L

K

D

A

A

S

A

K

K

L

V

P

A

I

V

D

E

R

-

V

-

N

-

I

T

G

G

V

V

P

Q

V

G

S

I

D

D

L

L

H
x
L

I

F

E

G

E

T

R

S

L

K

G

G

L

R

D

D

R

I

N

P

G

R

L

I

H

E

R

E

L

A

S

K

S

E

A

V

I

I

R

A

T

Y

A

I

K

R

-

E

-

A

A

A

F

P

G

H

I

V

E

E

Y

-

V

V

S
x
R

V

F

G

S

M

A

E

E

D

D

V

T

S

F

R

R

A

S

D

E

P

E

D

Q

F

D

A

L

L

L

T

A

V

V

A

Y

A

-

H

E

A

A

K

V

N

A

C

P

G

Y

A

V

S

D

R

R

I

V

R

G

L

L

S

A

D

D

S
x
T

L

V

G

G

Q

V

L

A

T

T

P

P

K

R

S

Q

M

V

E

Y

K

A

L

L

I

V

E

R

T

E

F

V

R

R

N

R

H

V

V

V

-

G

-

P

K

R

I

V

D

D

T

I

A

E

V

F

H
|
H

C

G

H
|
H

D

N

D

D

F

T

G

G

M

C

A

A

T

I

A

A

N

N

A

A

V

Y

T

E

A

A

L

I

E

E

C

A

G

G

A

A

D

T

Y

H

A

V

D

D

V

T

S

T

V

I

L

L

G

G

I

I

G

G

E

E

R

R

S

N

G

G

I

I

A

T

A

P

T

-

E

-

L

L

A

G

Y

F

L

L

A

A

L

R

R

M

C

Y

G

T

-

L

-

Q

-

P

-

E

-

Y

-

V

K

R

R

K

Y

Y

S

K

T

L

Q

E

K

M

I

L

K

P

A

E

L

L

C

D

S

R

M

M

V

V

A

A

L

R

E

M

A

V

G

G

V

V

V

E

V

I

P

P

R

F

T

N

K

N

A

Y

V

I

V

T

G

G

E

E

D

T

I

A

F

F

A

S

C

H

E

K

S

A

G

G

L

M

H

H

T

L

H

K

A

A

L

I

S

Y

K

I

S

N

P

P

E

E

L

A

F

Y

E

E

P

P

Y

Y

Q

P

P

P

E

E

S

V

V

F

G

G

I

V

S

K

R

R

K

K

L

L

A

I

V

I

active site: Q16 (= Q12)
binding 2-oxoglutaric acid: R12 (= R8), H72 (≠ W67), L94 (≠ H96), R127 (≠ S128), T160 (≠ S162), H189 (= H189)
binding magnesium ion: E13 (= E9), H189 (= H189), H191 (= H191)

2ztjA Crystal structure of homocitrate synthase from thermus thermophilus complexed with alpha-ketoglutarate (see paper)
31% identity, 84% coverage: 2:310/368 of query aligns to 6:311/312 of 2ztjA

query
sites
2ztjA

L

I

I

I

D

D

T

S

T

T

L

L

R
|
R

E
|
E

G

G

A

E

Q
|
Q

L

F

F

E

G

K

A

A

Y

N

F

F

N

S

L

T

S

Q

T

D

R

K

K

V

K

E

I

I

A

A

A

K

G

A

L

L

A

D

E

E

V

F

G

G

I

I

D

E

E

Y

I

I

E

E

L

V

G

T

W

T

-

P

I

V

G

A

Q

S

D

P

N

Q

L

S

G

R

T

K

L

D

A

A

E

E

Y

V

I

L

K

A

D

S

I

L

S

G

K

L

D

K

T

A

Y

K

L

V

S

V

V

T

W
x
H

T

I

P

Q

C

C

R

R

E

-

A

-

D

-

I

-

M

L

K

D

A

A

S

A

K

K

L

V

P

A

I

V

D

E

R

-

V

-

N

-

I

T

G

G

V

V

P

Q

V

G

S

I

D

D

L

L

H

-

I

-

E

-

R
x
L

L

F

G

G

L

T

D

G

R

R

N

D

G

-

L

-

L

I

H

P

R

R

L

I

S

I

S

E

A

E

I

A

R

K

T

E

A

V

K

I

A

A

F

Y

G

I

I

R

E

E

-

A

-

P

-

H

-

V

Y

E

V

V

S
x
R

V

F

G

S

M

A

E

E

D

D

V

T

S

F

R

R

A

S

D

E

P

E

D

Q

F

D

A

L

L

L

T

A

V

V

A

Y

A

-

H

E

A

A

K

V

N

A

C

P

G

Y

A

V

S

D

R

R

I

V

R

G

L

L

S
x
A

D

D

S
x
T

L

V

G

G

Q

V

L

A

T

T

P

P

K

R

S

Q

M

V

E

Y

K

A

L

L

I

V

E

R

T

E

F

V

R

R

N

R

H

V

V

V

-

G

-

P

K

R

I

V

D

D

T

I

A

E

V

F

H
|
H

C

G

H
|
H

D

N

D

D

F

T

G

G

M

C

A

A

T

I

A

A

N

N

A

A

V

Y

T

E

A

A

L

I

E

E

C

A

G

G

A

A

D

T

Y

H

A

V

D

D

V

T

S

T

V

I

L

L

G

G

I

I

G

G

E

E

R

R

S

N

G

G

I

I

A

T

A

P

T

-

E

-

L

L

A

G

Y

F

L

L

A

A

L

R

R

M

C

Y

G

T

-

L

-

Q

-

P

-

E

-

Y

-

V

K

R

R

K

Y

Y

S

K

T

L

Q

E

K

M

I

L

K

P

A

E

L

L

C

D

S

R

M

M

V

V

A

A

L

R

E

M

A

V

G

G

V

V

V

E

V

I

P

P

R

F

T

N

K

N

A

Y

V

I

V

T

G

G

E

E

D

T

I

A

F

F

A

S

C

H

E

K

S

A

G

G

L

M

H

H

T

L

H

K

A

A

L

I

S

Y

K

I

S

N

P

P

E

E

L

A

F

Y

E

E

P

P

Y

Y

Q

P

P

P

E

E

S

V

V

F

G

G

I

V

S

K

R

R

K

K

L

L

A

I

V

I

active site: Q16 (= Q12)
binding 2-oxoglutaric acid: R12 (= R8), H72 (≠ W67), L94 (≠ R100), R125 (≠ S128), A156 (≠ S160), T158 (≠ S162), H187 (= H189), H189 (= H191)
binding copper (ii) ion: E13 (= E9), H187 (= H189), H189 (= H191)

3a9iA Crystal structure of homocitrate synthase from thermus thermophilus complexed with lys (see paper)
31% identity, 82% coverage: 2:304/368 of query aligns to 5:306/347 of 3a9iA

query
sites
3a9iA

L

I

I

I

D

D

T

S

T

T

L

L

R
|
R

E
|
E

G

G

A

E

Q

Q

L

F

F

E

G

K

A

A

Y

N

F

F

N

S

L

T

S

Q

T

D

R

K

K

V

K

E

I

I

A

A

A

K

G

A

L

L

A

D

E

E

V

F

G

G

I

I

D

E

E

Y

I

I

E

E

L

V

G

T

W

T

-

P

I

V

G

A

Q

S

D

P

N

Q

L

S

G

R

T

K

L

D

A

A

E

E

Y

V

I

L

K

A

D

S

I

L

S

G

K

L

D

K

T

A

Y

K

L

V

S

V

V

T

W

H

T

I

P

Q

C

C

R

R

E

-

A

-

D

-

I

-

M

L

K

D

A

A

S

A

K

K

L

V

P

A

I

V

D

E

R

-

V

-

N

-

I

T

G

G

V

V

P

Q

V

G

S

I

D
|
D

L

L

H

L

I

F

E

G

E

T

R

S

L

K

G

Y

L

L

D

D

R

I

N

P

G

R

L

I

H

E

R

E

L

A

S

K

S

E

A

V

I

I

R

A

T

Y

A

I

K

R

-

E

-

A

A

A

F

P

G

H

I

V

E

E

Y

-

V

V

S

R

V

F

G
x
S

M

A

E

E

D

D

V

T

S

F

R

R

A

S

D

E

P

E

D

Q

F

D

A

L

L

L

T

A

V

V

A

Y

A

-

H

E

A

A

K

V

N

A

C

P

G

Y

A

V

S

D

R

R

I

V

R

G

L

L

S

A

D

D

S
x
T

L

V

G

G

Q

V

L

A

T

T

P

P

K

R

S

Q

M

V

E

Y

K

A

L

L

I

V

E

R

T

E

F

V

R

R

N

R

H

V

V

V

-

G

-

P

K

R

I

V

D

D

T

I

A

E

V

F

H
|
H

C

G

H
|
H

D

N

D

D

F

T

G

G

M

C

A

A

T

I

A

A

N

N

A

A

V

Y

T

E

A

A

L

I

E

E

C

A

G

G

A

A

D

T

Y

H

A

V

D

D

V

T

S

T

V

I

L

L

G

G

I

I

G

G

E

E

R

R

S

N

G

G

I

I

A

T

A

P

T

-

E

-

L

L

A

G

Y

F

L

L

A

A

L

R

R

M

C

Y

G

T

-

L

-

Q

-

P

-

E

-

Y

-

V

K

R

R

K

Y

Y

S

K

T

L

Q

E

K

M

I

L

K

P

A

E

L

L

C

D

S

R

M

M

V

V

A

A

L

R

E

M

A

V

G

G

V

V

V

E

V

I

P

P

R

F

T

N

K

N

A

Y

V

I

V

T

G

G

E

E

D

T

I

A

F

F

A

S

C

H

E

K

S

A

G

G

L

M

H

H

T

L

H

K

A

A

L

I

S

Y

K

I

S

N

P

P

E

E

L

A

F

Y

E

E

P

P

Y

Y

Q

P

P

P

E

E

S

V

V

F

G

G

I

V

binding cobalt (ii) ion: E12 (= E9), H188 (= H189), H190 (= H191)
binding lysine: R11 (= R8), D91 (= D94), S128 (≠ G130), T159 (≠ S162), H188 (= H189), H190 (= H191)

4ov4A Isopropylmalate synthase binding with ketoisovalerate (see paper)
26% identity, 98% coverage: 4:363/368 of query aligns to 8:379/379 of 4ov4A

query
sites
4ov4A

D

D

T

V

T

T

L

L

R
|
R

E
x
D

G

G

A

N

Q
|
Q

L

A

F

L

G

K

A

R

Y

P

F

W

N

T

L

I

S

D

T

E

R

K

K

I

K

E

I

V

A

F

A

D

G

L

L

L

A

V

E

E

V

L

G

N

I

V

D

D

E

G

I

I

E

E

L

V

G

G

W

F

I

P

G

S

Q

S

D

N

N

E

-

T

-

E

-

F

-

H

-

T

-

C

-

Q

-

V

L

L

G

S

T

K

L

R

A

A

E

P

Y

K

I

G

K

K

D

P

I

I

-

A

-

L

-

S

-

R

-

A

S

N

K

Q

D

N

T

E

Y

I

L

A

S

V

V

T

W

W

T

E

P

A

C

I

R

Q

E

K

A

A

D

D

I

C

M

-

K

-

A

-

S

-

K

-

L

-

P

-

I

-

D

P

R

R

V

M

N

H

I

I

G

V

V

Y

P

P

V

V

S

S

D

D

L

F

H

S

I

I

E

K

E

H

R

V

L

L

G

K

L

I

D

S

R

E

N

K

G

E

L

V

L

L

H

Q

R

K

L

I

S

R

S

N

A

S

I

I

R

S

T

F

A

A

K

R

A

S

F

I

-

V

-

G

-

P

G

G

I

I

E

E

Y

-

V

I

S

Q

V

F

G

S

M

G

E

E

D

H

V

F

S

G

R

D

A

A

D

I

P

E

D

N

F

F

A

A

L

F

T

T

V

K

A

E

A

A

H

F

-

L

-

T

A

A

K

I

N

E

C

A

G

G

A

A

S

N

R

I

I

I

R

N

L

L

S
x
P

D

N

S
x
T

L

V

G

E

Q

R

L

Y

T

R

P

P

K

M

S

V

M

F

E

V

K

N

L

M

I

V

E

K

T

E

F

I

R

K

N

D

H

V

V

V

K

K

I

-

D

D

T

K

A

A

V

I

-

I

-

S

-

I

H
|
H

C

T

H
|
H

D

N

D

D

F

L

G

G

M

M

A

A

T

T

A

A

N

T

A

S

V

V

T

E

A

S

L

V

E

Y

C

V

G

G

A

A

D

E

Y

Q

A

I

D

E

V

V

S

A

V

L

L

N

G

G

I

L

G

G

E

E

R

R

S

A

G

G

I

N

A

T

A

N

T

L

E

Y

E

E

L

T

A

A

A

I

Y

A

L

L

A

H

L

Q

R

N

C

G

G

E

K

N

K

L

R

N

Y

I

S

N

T

F

Q

Q

K

R

I

I

K

Y

A

P

L

T

C

A

S

K

M

R

V

I

A

S

L

E

E

L

A

T

G

G

V

I

V

P

V

I

P

G

R

E

T

K

K

T

A

P

V

I

G

G

E

E

D

D

I

I

F

F

A

S

C

H

E

R

S

S

G

G

L

I

H

H

T

Q

H

H

A

-

L

-

S

-

K

Q

S

S

P

K

E

G

L

A

F

Y

E

R

P

T

Y

F

Q

S

P

P

E

E

S

F

V

V

G

G

I

R

S

M

R

D

K

K

-

E

-

T

L

I

A

S

V

F

G

T

G

N

K

Q

S

S

G

G

K

H

A

K

A

A

V

I

K

E

S

F

A

L

L

L

K

H

D

Q

C

R

G

G

V

I

E

Q

N

V

D

S

P

K

K

E

D

G

I

I

T

H

A

H

L

L

T

F

M

S

A

L

V

A

R

K

Q

S

L

I

S

S

R

R

L

E

-

N

K

N

R

R

P

E

L

I

T

T

R

E

S

A

E

E

F

L

I

V

K

A

L

L

S

S

S

Q

active site: Q16 (= Q12)
binding 3-methyl-2-oxobutanoic acid: R12 (= R8), P174 (≠ S160), T176 (≠ S162), H205 (= H189), H207 (= H191)
binding zinc ion: D13 (≠ E9), H205 (= H189), H207 (= H191)

4ov9A Structure of isopropylmalate synthase binding with alpha- isopropylmalate (see paper)
27% identity, 98% coverage: 4:362/368 of query aligns to 8:380/380 of 4ov9A

query
sites
4ov9A

D

D

T

V

T

T

L

L

R
|
R

E
x
D

G

G

A

N

Q
|
Q

L

A

F

L

G

K

A

R

Y

P

F

W

N

T

L

I

S

D

T

E

R

K

K

I

K

E

I

V

A

F

A

D

G

L

L

L

A

V

E

E

V

L

G

N

I

V

D

D

E

G

I

I

E

E

L

V

G

G

W

F

I

P

G

S

Q

S

D

N

N

E

-

T

-

E

-

F

-

H

-

T

-

C

-

Q

-

V

L

L

G

S

T

K

L

R

A

A

E

P

Y

K

I

G

K

K

D

P

I

I

-

A

-
x
L

-

S

-

R

-

A

S

N

K

Q

D

N

T

E

Y

I

L

A

S

V

V

T

W

W

T

E

P

A

C

I

R

Q

E

K

A

A

D

D

I

C

M

-

K

-

A

-

S

-

K

-

L

-

P

-

I

-

D

P

R

R

V

M

N

H

I

I

G

V

V

Y

P

P

V

V

S

S

D

D

L

F

H

S

I

I

E

K

E

H

R

V

L

L

G

K

L

I

D

S

R

E

N

K

G

E

L

V

L

L

H

Q

R

K

L

I

S

R

S

N

A

S

I

I

R

S

T

F

A

A

K

R

A

S

F

I

-

V

-

G

-

P

G

G

I

I

E

E

Y

-

V

I

S

Q

V

F

G

S

M

G

E

E

D

H

V

F

S

G

R

D

A

A

D

I

P

E

D

N

F

F

A

A

L

F

T

T

V

K

A

E

A

A

H

F

-

L

-

T

A

A

K

I

N

E

C

A

G

G

A

A

S

N

R

I

I

I

R

N

L

L

S

P

D

N

S
x
T

L

V

G

E

Q

R

L

Y

T

R

P

P

K

M

S

V

M

F

E

V

K

N

L

M

I

V

E

K

T

E

F

I

R

K

N

D

H

V

V

V

K

K

I

-

D

D

T

K

A

A

V

I

-

I

-

S

-

I

H
|
H

C

T

H
|
H

D

N

D

D

F

L

G

G

M

M

A

A

T

T

A

A

N

T

A

S

V

V

T

E

A

S

L

V

E

Y

C

V

G

G

A

A

D

E

Y

Q

A

I

D

E

V

V

S

A

V

L

L

N

G

G

I

L

G

G

E

E

R

R

S

A

G

G

I

N

A

T

A

N

T

L

E

Y

E

E

L

T

A

A

A

I

Y

A

L

L

A

H

L

Q

R

N

C

G

G

E

K

N

K

L

R

N

Y

I

S

N

T

F

Q

Q

K

R

I

I

K

Y

A

P

L

T

C

A

S

K

M

R

V

I

A

S

L

E

E

L

A

T

G

G

V

I

V

P

V

I

P

G

R

E

T

K

K

T

A

P

V

I

G

G

E

E

D

D

I

I

F

F

A

S

C

H

E

R

S

S

G

G

L

I

H

H

T

-

H

Q

A

T

L

L

S

H

K

Q

S

S

P

K

E

G

L

A

F

Y

E

R

P

T

Y

F

Q

S

P

P

E

E

S

F

V

V

G

G

I

R

S

M

R

D

K

K

-

E

-

T

L

I

A

S

V

F

G

T

G

N

K

Q

S

S

G

G

K

H

A

K

A

A

V

I

K

E

S

F

A

L

L

L

K

H

D

Q

C

R

G

G

V

I

E

Q

N

V

D

S

P

K

K

E

D

G

I

I

T

H

A

H

L

L

T

F

M

S

A

L

V

A

R

K

Q

S

L

I

S

S

R

R

L

E

-

N

K

N

R

R

P

E

L

I

T

T

R

E

S

A

E

E

F

L

I

V

K

A

L

L

S

S

active site: Q16 (= Q12)
binding (2S)-2-hydroxy-2-(propan-2-yl)butanedioic acid: R12 (= R8), L73 (vs. gap), T176 (≠ S162), H205 (= H189), H207 (= H191)
binding zinc ion: D13 (≠ E9), H205 (= H189), H207 (= H191)

3rmjB Crystal structure of truncated alpha-isopropylmalate synthase from neisseria meningitidis (see paper)
29% identity, 76% coverage: 1:280/368 of query aligns to 5:296/308 of 3rmjB

query
sites
3rmjB

M

I

L

I

I

F

D

D

T

T

L

L

R

R

E
x
D

G

G

A

E

Q
|
Q

L

S

F

P

G

G

A

A

Y

A

F

M

N

T

L

K

S

E

T

E

R

K

K

I

K

R

I

V

A

A

A

R

G

Q

L

L

A

E

E

K

V

L

G

G

I

V

D

D

E

I

I

I

E

E

L

A

G

G

W

F

I

A

G

A

Q

A

D

S

-

P

-

G

N

D

L

F

G

E

T

A

L

V

A

N

E

A

Y

I

I

A

K

K

D

T

I

I

S

T

K

K

D

S

T

T

Y

V

L

C

S

S

V

L

W

-

T

S

P

R

C

A

R

I

E

E

A

R

D

D

I

I

M

R

K

Q

A

A

S

G

K

E

L

A

-

V

-

A

-

P

-

A

P

P

I

K

D

K

R

R

V

I

N

H

I

T

G

F

V

I

P

A

V

T

S

S

D

P

L

I

H

H

I

M

E

E

E

Y

R

K

L

L

G

K

L

M

D

K

R

P

N

K

G

Q

L

V

L

I

H

E

R

A

L

A

S

V

S

K

A

A

I

V

R

K

T

I

A

A

K

R

A

E

F

Y

G

-

I

T

E

D

Y

D

V

V

S

E

V

F

G

S

M

C

E

E

D

D

V

A

S

L

R

R

A

S

D

E

P

I

D

D

F

F

A

L

L

A

T

E

V

I

A

C

A

G

H

A

A

V

K

I

N

E

C

A

G

G

A

A

S

T

R

T

I

I

R

N

L

I

S

P

D

D

S

T

L

V

G

G

Q

Y

L

S

T

I

P

P

K

Y

S

K

M

T

E

E

K

E

-

F

-

R

-

E

L

L

I

I

E

A

T

K

F

T

R

P

N

N

H

G

V

G

K

K

I

V

D

V

T

W

A

S

V

A

H
|
H

C

C

H
|
H

D

N

D

D

F

L

G

G

M

L

A

A

T

V

A

A

N

N

A

S

V

L

T

A

A

A

L

L

E

K

C

G

G

G

A

A

D

R

Y

Q

A

V

D

E

V

C

S

T

V

V

L

N

G

G

I

L

G

G

E

E

R

R

S

A

G

G

I
x
N

A

A

A

S

T

V

E

E

L

I

A

V

A

M

Y

A

L

L

A

K

L

V

R

R

C

H

G

D

-

L

-

F

-

G

-

L

K

E

K

T

R

G

Y

I

S

D

T

T

Q

T

K

Q

I

I

K

V

A

P

L

S

C

S

S

K

M

L

V

V

A

S

L

T

E

I

A

T

G

G

V

Y

V

P

V

V

P

Q

R

P

T

N

K

K

A

A

V

I

V

V

G

G

E

A

D

N

I

A

F

F

A

S

C

H

E

E

S

T

active site: Q16 (= Q12)
binding manganese (ii) ion: D13 (≠ E9), H201 (= H189), H203 (= H191), N237 (≠ I225)

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, 89% coverage: 2:328/368 of query aligns to 10:347/516 of Q8F3Q1

query
sites
Q8F3Q1

L

I

I

L

D

D

T

V

T

T

L

L

R
|
R

E
x
D

G

G

A

E

Q

Q

L

T

F

R

G

G

A

V

Y

S

F

F

N

S

L

T

S

S

T

E

R

K

K

L

K

N

I

I

A

A

A

K

G

F

L

L

A

L

E

Q

-

K

V

L

G

N

I

V

D

D

E

R

I

V

E

E

L

I

G

A

-

S

-

A

W

R

I

V

G

S

Q

K

D

G

N

E

L

L

G

E

T

T

L

V

A

Q

E

K

Y

I

I

M

K

E

D

W

I

A

S

A

K

T

D

E

T

Q

Y

L

-

T

-

E

-

R

-

I

-

E

-

I

L
|
L

S

G

V
x
F

W

V

T

D

P

G

C

N

R

K

E

T

A

V

D

D

I

W

M

I

K

K

A

D

S

S

K

G

L

A

P

K

I

V

D

-

R

-

V

L

N

N

I

L

G
x
L

V

T

P

K

V

G

S

S

D

L

L

H

H

H

I

L

E

E

E

K

R

Q

L

L

G

G

L

K

D

T

R

P

N

K

G

E

L

F

H

T

R

D

L

V

S

S

S

F

A

V

I

I

R

E

T

Y

A

A

K

I

A

K

F

S

G

G

I

L

E

K

Y

-

V

I

S

N

V

V

G
x
Y

M

L

E
|
E

D

D

V

W

S

S

-

N

-

G

-

F

R

R

A

N

D

S

P

P

D

D

F

Y

A

V

L

K

T

S

V

L

A

V

A

E

H

H

A

L

K

S

N

K

C

E

G

H

A

I

S

E

R

R

I

I

R

F

L

L

S

P

D

D

S
x
T

L

L

G

G

Q

V

L

L

T

S

P

P

K

E

S

E

M

T

E

F

K

Q

L

G

I

V

E

D

T

S

F

L

-

I

R

Q

N

K

H

Y

V

P

K

D

I

I

D

H

T

F

A

E

V

F

H

H

C

G

H

H

D

N

D

D

F

Y

G

D

M

L

A

S

T

V

A

A

N

N

A

S

V

L

T

Q

A

A

L

I

E

R

C

A

G

G

A

V

D

K

Y

G

A

L

D

H

V

A

S

S

V

I

L

N

G

G

I

L

G

G

E

E

R

R

S

A

G

G

I

N

A

T

A

P

T

L

E

E

E

A

L

L

A

V

A

T

Y

T

L

I

A

H

L

D

R

K

C

S

G

N

K

S

K

K

R

T

Y

N

S

I

T

N

Q

E

-

I

K

A

I

I

K

T

A

E

L

A

C

S

S

R

M

L

V

V

A

E

L

V

E

F

A

S

G

G

V

K

V

R

V

I

P

S

R

A

T

N

K

R

A

P

V

I

V

V

G

G

E

E

D

D

I

V

F

F

A

T

C

Q

E

T

S

A

G

G

L

V

H
|
H

T

A

H
x
D

A

G

L

D

S

K

K

K

S

G

P
x
N

E
x
L

L
x
Y

F

A

E

N

P

P

Y

I

Q

L

P

P

E

E

S

R

V

F

G

G

I

R

S

K

R

R

K

S

L

Y

A

A

V

L

G

G

G

K

K

L

S

A

G

G

K

K

A

A

A

S

V

I

K

S

S

E

A

N

L

V

K

K

D

Q

C

L

G

G

V

M

R16 (= R8) mutation R->K,Q: Loss of activity.
RD 16:17 (≠ RE 8:9) binding pyruvate
D17 (≠ E9) 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 (= L64) 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 (≠ V66) mutation to A: 5-fold increase in Km for acetyl-CoA and 120-fold decrease in kcat.
L104 (≠ G89) mutation to V: 1.8-fold increase in Km for pyruvate and 3.4-fold decrease in kcat.
Y144 (≠ G130) 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 (= E132) mutation E->D,Q: Minor effects on the binding of acetyl-CoA, but causes a strong decrease in kcat.
T179 (≠ S162) binding pyruvate; mutation to A: 16.4-fold increase in Km for pyruvate and 186-fold decrease in kcat.
H302 (= H283) mutation H->A,N: Loss of activity.
D304 (≠ H285) mutation to A: 5.2-fold increase in Km for acetyl-CoA and 16.6-fold decrease in kcat.
N310 (≠ P291) mutation to A: 2.2-fold increase in Km for acetyl-CoA and 1.7-fold decrease in kcat.
L311 (≠ E292) mutation to A: 8-fold increase in Km for acetyl-CoA and 6-fold decrease in kcat.
Y312 (≠ L293) 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.

3bliA Crystal structure of the catalytic domain of licms in complexed with pyruvate and acetyl-coa (see paper)
25% identity, 80% coverage: 2:294/368 of query aligns to 4:307/311 of 3bliA

query
sites
3bliA

L

I

I

L

D

D

T

V

T

T

L

L

R
|
R

E
x
D

G

G

A

E

Q
|
Q

L

T

F

R

G

G

A

V

Y

S

F

F

N

S

L

T

S

S

T

E

R

K

K

L

K

N

I

I

A

A

A

K

G

F

L

L

A

L

E

Q

-

K

V

L

G

N

I

V

D

D

E

R

I

V

E

E

L

I

G

A

-

S

-

A

W
x
R

I
x
V

G

S

Q

K

D

G

N

E

L

L

G

E

T

T

L

V

A

Q

E

K

Y

I

I

M

K

E

D

W

I

A

S

A

K

T

D

E

T

Q

Y

L

-

T

-

E

-

R

-

I

-

E

-

I

L

L

S

G

V

F

W

V

T

D

P

G

C

N

R

K

E

T

A

V

D

D

I

W

M

I

K

K

A

D

S

S

K

G

L

A

P

K

I

V

D

-

R

-

V

L

N

N

I

L

G

L

V

T

P

K

V

G

S

S

D

L

L

H

H

H

I

L

E

E

E

K

R

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L

L

G

G

L

K

D

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N

K

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A

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I

I

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Y

A

A

K

I

A

K

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G

G

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-

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x
Y

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E

D

D

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W

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S

-

N

-

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R

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Y

A

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H

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N

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A

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V

A

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L

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K

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F

active site: Q14 (= Q12)
binding acetyl coenzyme *a: Q14 (= Q12), R47 (≠ W42), V48 (≠ I43), E140 (= E132)
binding pyruvic acid: R10 (= R8), Y138 (≠ G130), P171 (≠ S160), T173 (≠ S162)
binding zinc ion: D11 (≠ E9), H201 (= H189), H203 (= H191)

Q8TB92 3-hydroxy-3-methylglutaryl-CoA lyase, cytoplasmic; 3-hydroxy-3-methylglutaryl-CoA lyase-like protein 1; HMGCL-like 1; Endoplasmic reticulum 3-hydroxy-3-methylglutaryl-CoA lyase; er-cHL; EC 4.1.3.4 from Homo sapiens (Human) (see 2 papers)
31% identity, 38% coverage: 97:235/368 of query aligns to 188:330/370 of Q8TB92

query
sites
Q8TB92

I

I

E

E

R

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M

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G

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D

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H

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H

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G

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L237 (≠ A149) mutation to S: Abolishes catalytic activity.
H278 (= H189) mutation to R: Abolishes catalytic activity.

Sites not aligning to the query:

2 modified: N-myristoyl glycine; G→A: Abolishes myristoylation and induces a subcellular location change.
86 R→Q: Abolishes catalytic activity.

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)
27% identity, 64% coverage: 2:235/368 of query aligns to 35:285/325 of P35914

query
sites
P35914

L

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H

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D

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G

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G

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E37 (≠ D4) to K: in HMGCLD; activity lower than 5% respect to the wild-type; mutation to D: Normal activity.
R41 (= R8) to Q: in HMGCLD; loss of activity and of proton exchange; dbSNP:rs121964997; mutation to M: Reduced activity, and loss of proton exchange.
D42 (≠ E9) 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 (≠ G15) to N: in HMGCLD; abolishes almost all enzymatic activity
E72 (= E39) mutation to A: Loss of activity, and reduced affinity for metal cofactor and substrate.
S142 (≠ D104) to F: in HMGCLD; activity lower than 5% respect to the wild-type
C174 (≠ M131) to Y: in HMGCLD; activity lower than 5% respect to the wild-type; dbSNP:rs765475941
F192 (≠ A149) to S: in HMGCLD; activity lower than 5% respect to the wild-type
I200 (= I157) to F: in HMGCLD; activity lower than 5% respect to the wild-type
G203 (≠ S160) to E: in HMGCLD; complete loss of activity; dbSNP:rs1553131940
D204 (= D161) mutation to A: Reduced activity, and reduced affinity for metal cofactor and substrate.
H233 (= H189) to R: in HMGCLD; loss of activity; dbSNP:rs727503963; mutation to A: Loss of activity, and reduced proton exchange rate.
E279 (= E229) mutation to A: Reduced thermal stability, but normal activity.
D280 (≠ E230) 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_027177793.1 NCBI__GCF_000429985.1:WP_027177793.1
MLIDTTLREGAQLFGAYFNLSTRKKIAAGLAEVGIDEIELGWIGQDNLGTLAEYIKDISK
DTYLSVWTPCREADIMKASKLPIDRVNIGVPVSDLHIEERLGLDRNGLLHRLSSAIRTAK
AFGIEYVSVGMEDVSRADPDFALTVAAHAKNCGASRIRLSDSLGQLTPKSMEKLIETFRN
HVKIDTAVHCHDDFGMATANAVTALECGADYADVSVLGIGERSGIAATEELAAYLALRCG
KKRYSTQKIKALCSMVALEAGVVVPRTKAVVGEDIFACESGLHTHALSKSPELFEPYQPE
SVGISRKLAVGGKSGKAAVKSALKDCGVENDPKDITALTMAVRQLSSRLKRPLTRSEFIK
LSSGEHLS

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