SitesBLAST

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)
40% identity, 86% coverage: 2:265/307 of query aligns to 32:295/325 of P35914

query
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P35914

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E37 (≠ D7) to K: in HMGCLD; activity lower than 5% respect to the wild-type; mutation to D: Normal activity.
R41 (= R11) to Q: in HMGCLD; loss of activity and of proton exchange; dbSNP:rs121964997; mutation to M: Reduced activity, and loss of proton exchange.
D42 (= D12) 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 (≠ G18) to N: in HMGCLD; abolishes almost all enzymatic activity
E72 (= E42) mutation to A: Loss of activity, and reduced affinity for metal cofactor and substrate.
S142 (= S112) to F: in HMGCLD; activity lower than 5% respect to the wild-type
C174 (= C144) to Y: in HMGCLD; activity lower than 5% respect to the wild-type; dbSNP:rs765475941
F192 (≠ M162) to S: in HMGCLD; activity lower than 5% respect to the wild-type
I200 (= I170) to F: in HMGCLD; activity lower than 5% respect to the wild-type
G203 (≠ A173) to E: in HMGCLD; complete loss of activity; dbSNP:rs1553131940
D204 (= D174) mutation to A: Reduced activity, and reduced affinity for metal cofactor and substrate.
H233 (= H203) to R: in HMGCLD; loss of activity; dbSNP:rs727503963; mutation to A: Loss of activity, and reduced proton exchange rate.
E279 (= E249) mutation to A: Reduced thermal stability, but normal activity.
D280 (= D250) mutation to A: Normal activity.

Sites not aligning to the query:

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

3mp3B Crystal structure of human lyase in complex with inhibitor hg-coa (see paper)
40% identity, 86% coverage: 2:265/307 of query aligns to 5:268/296 of 3mp3B

query
sites
3mp3B

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binding (3R,5S,9R,21S)-1-[(2R,3S,4R,5R)-5-(6-amino-9H-purin-9-yl)-4-hydroxy-3-(phosphonooxy)tetrahydrofuran-2-yl]-3,5,9,21-tetrahydroxy-8,8-dimethyl-10,14,19-trioxo-2,4,6-trioxa-18-thia-11,15-diaza-3,5-diphosphatricosan-23-oic acid 3,5-dioxide: R14 (= R11), D15 (= D12), Q18 (= Q15), F49 (= F46), V50 (= V47), S51 (= S48), W54 (≠ A51), P81 (= P78), N82 (= N79), K84 (= K81), G85 (= G82), N111 (= N108), R122 (≠ V119), Y140 (= Y137), S142 (≠ A139), T178 (= T175), H206 (= H203)
binding magnesium ion: D15 (= D12), H206 (= H203), H208 (= H205)

2cw6A Crystal structure of human hmg-coa lyase: insights into catalysis and the molecular basis for hydroxymethylglutaric aciduria (see paper)
40% identity, 86% coverage: 2:265/307 of query aligns to 5:268/296 of 2cw6A

query
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2cw6A

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binding 3-hydroxypentanedioic acid: Q18 (= Q15), F100 (≠ V97)
binding magnesium ion: D15 (= D12), H206 (= H203), H208 (= H205), N248 (= N245)

3mp5B Crystal structure of human lyase r41m in complex with hmg-coa (see paper)
40% identity, 86% coverage: 2:265/307 of query aligns to 5:268/296 of 3mp5B

query
sites
3mp5B

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binding 3-hydroxy-3-methylglutaryl-coenzyme a: D15 (= D12), Q18 (= Q15), S51 (= S48), W54 (≠ A51), F100 (≠ V97), N111 (= N108), N113 (≠ R110), Y140 (= Y137), S142 (≠ A139), T178 (= T175), C239 (= C236)
binding magnesium ion: D15 (= D12), H206 (= H203), H208 (= H205)

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)
37% identity, 86% coverage: 3:265/307 of query aligns to 78:340/370 of Q8TB92

query
sites
Q8TB92

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L

V

F

M

S

K

R

G

L

I

P

H

A

Q

S

Y

D

P

K

G

V

V

R

R

Y

Y

A

P

G

V

L

L

V

T

P

P

N

N

M

L

K

Q

G

G

Y

F

Q

H

L

H

A

A

T

V

A

A

G

G

A

A

K

T

V

E

V

I

N

S

V

V

V

F

L

G

S

A

V

A

T

S

D

E

T

S

M

F

N

S

Q

K

K

K

N

N

I

I

R

N

M

C

S

S

L

I

D

E

E

E

T

S

A

M

D

G

V

K

C

F

K

E

A

E

I

V

V

V

E

K

R

S

G

A

H

R

L

H

E

M

G

N

V

I

E

P

V

A

Q

R

A

G

Y

Y

L

V

A

S

V

C

A

A

F

L

E

G

C

C

P

P

F

Y

E

E

G

G

L

S

V

I

D

T

P

P

E

Q

V

K

V

V

A

T

R

E

Y

V

A

S

R

K

L

R

M
x
L

H

Y

S

G

A

M

G

G

A

C

A

Y

K

E

I

I

I

S

I

L

A

G

D

D

T

T

I

I

G

G

A

V

A

G

N

T

P

P

T

G

Q

S

V

M

R

K

Q

R

V

M

L

L

D

E

L

S

V

V

V

M

P

K

E

E

V

I

G

P

A

P

D

G

R

A

L

L

S

A

C

V

H
|
H

F

C

H

H

D

D

T

T

R

Y

G

G

M

Q

A

A

L

L

A

A

N

N

I

I

T

L

V

T

A

A

V

L

D

Q

R

M

G

G

V

I

C

N

E

V

F

V

D

D

S

S

S

A

I

V

G

S

G

G

L

L

G

G

C

C

P

P

F

Y

S

A

P

K

G

G

A

A

T

S

G

G

N

N

V

V

A

A

T

T

E

E

D

D

V

L

V

I

L

Y

L

M

L

L

N

N

S

G

M

L

G

G

H

L

D

N

T

T

G

G

I

V

D

N

R86 (= R11) mutation to Q: Abolishes catalytic activity.
L237 (≠ M162) mutation to S: Abolishes catalytic activity.
H278 (= H203) 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.

6ndsA Structure of an hmg-coa lyase from acenitobacter baumannii in complex with coenzyme a and 3-methylmalate
39% identity, 90% coverage: 5:279/307 of query aligns to 10:280/305 of 6ndsA

query
sites
6ndsA

V

V

N

Q

D

E

V

V

G

S

P

P

R

R

D
|
D

G

G

L

L

Q

Q

S

I

Q

E

G

P

K

T

T

W

L

V

S

P

V

T

D

D

A

K

R

K

A

I

Q

D

L

L

I

I

E

N

A

Q

L

L

V

S

G

T

A

M

G

G

L

F

R

S

N

R

I

I

E

E

A

A

G

G

S

S

F

F

V
|
V

S
|
S

P

P

K

K

A

A

V
x
I

P

P

Q

N

M

L

A

R

G

D

T

G

D

E

E

E

L

V

F

F

S

T

R

G

L

I

P

T

A

R

S

H

D

K

K

D

V

I

R

I

Y

Y

A

V

G

G

L

L

V

I

P

P

N
|
N

M

L

K

K

G
|
G

Y

A

Q

L

L
x
R

A

A

T

V

A

E

A

A

G

N

A

A

K

N

V

E

V

L

N

N

V

L

V

V

L

L

S

S

V

A

T

S

D

Q

T

T

M

H

N

N

Q

L

K

A

N
|
N

I
x
M

R
|
R

M

M

S

T

L

K

D

A

E

Q

T

S

A

F

D

A

V

G

C

F

K

T

A

E

I

I

V

V

E

E

R

Q

G

-

H

-

L

L

E

Q

G

G

-

K

V

T

E

Q

V

F

Q

N

A

G

Y

T

L

V

A

A

V

T

A

T

F

F

E

G

C

C

P

P

F

F

E

E

G

G

L

K

V

I

D

S

P

E

E

R

V

E

V

V

A

F

R

S

Y

L

A

V

R

E

L

H

M

Y

H

L

S

K

A

L

G

G

A

I

A

H

K

N

I

I

I

T

I

L

A

A

D

D

T

T

I

T

G

G

A

M

A

A

N

N

P

P

T

V

Q

Q

V

V

R

K

Q

R

V

I

L

V

D

S

L

H

V

V

V

L

P

S

E

L

V

I

G

S

A

P

D

E

R

Q

L

L

S

T

C

L

H
|
H

F

F

H
|
H

D

N

T

T

R

R

G

G

M

L

A

G

L

L

A

T

N

N

I

V

T

L

V

A

A

A

V

Y

D

E

R

V

G

G

V

A

C

R

E

R

F

F

D

D

S

A

I

L

G

G

L

L

G

G

C

C

P

P

F

F

S

A

P

P

G

G

A

A

T

S

G

G

N

N

V

I

A

C

T

T

E

E

D

D

V

L

V

V

L

N

L

M

L

C

N

E

S

E

M

I

G

G

H

I

D

P

T

T

G

T

I

I

D

-

P

-

L

-

D

D

L

L

V

D

P

A

L

L

V

I

H

Q

L

L

A

S

E

R

E

T

L

L

binding coenzyme a: V52 (= V47), S53 (= S48), I57 (≠ V52), N84 (= N79), G87 (= G82), R90 (≠ L85), N113 (= N108), M114 (≠ I109), R115 (= R110)
binding zinc ion: D17 (= D12), H207 (= H203), H209 (= H205)

1ydnA Crystal structure of the hmg-coa lyase from brucella melitensis, northeast structural genomics target lr35. (see paper)
40% identity, 86% coverage: 3:265/307 of query aligns to 4:266/283 of 1ydnA

query
sites
1ydnA

V

V

R

E

V

I

N

V

D

E

V

M

G

A

P

A

R

R

D
|
D

G

G

L

L

Q

Q

S

N

Q

E

G

K

K

R

T

F

L

V

S

P

V

T

D

A

A

D

R

K

A

I

Q

A

L

L

I

I

E

N

A

R

L

L

V

S

G

D

A

C

G

G

L

Y

R

A

N

R

I

I

E

E

A

A

G

T

S

S

F

F

V

V

S

S

P

P

K

K

A

W

V

V

P

P

Q

Q

M

L

A

A

G

D

T

S

D

R

E

E

L

V

F

M

S

A

R

G

L

I

P

R

A

R

S

A

D

D

K

G

V

V

R

R

Y

Y

A

S

G

V

L

L

V

V

P

P

N

N

M

M

K

K

G

G

Y

Y

Q

E

L

A

A

A

T

A

A

A

G

H

A

A

K

D

V

E

V

I

N

A

V

V

V

F

L

I

S

S

V

A

T

S

D

E

T

G

M

F

N

S

Q

K

K

A

N

N

I

I

R

N

M

C

S

T

L

I

D

A

E

E

T

S

A

I

D

E

V

R

C

L

K

S

A

P

I

V

V

I

E

G

R

A

G

A

H

I

L

N

E

D

G

G

V

L

E

A

V

I

Q

R

A

G

Y

Y

L

V

A

S

V

C

A

V

F

V

E

E

C

C

P

P

F

Y

E

D

G

G

L

P

V

V

D

T

P

P

E

Q

V

A

V

V

A

A

R

S

Y

V

A

T

R

E

L

Q

M

L

H

F

S

S

A

L

G

G

A

C

A

H

K

E

I

V

I

S

I

L

A

G

D

D

T

T

I

I

G

G

A

R

A

G

N

T

P

P

T

D

Q

T

V

V

R

A

Q

A

V

M

L

L

D

D

L

A

V

V

V

L

P

A

E

I

V

A

G

P

A

A

D

H

R

S

L

L

S

A

C

G

H
|
H

F

Y

H
|
H

D

D

T

T

R

G

G

G

M

R

A

A

L

L

A

D

N

N

I

I

T

R

V

V

A

S

V

L

D

E

R

K

G

G

V

L

C

R

E

V

F

F

D

D

S

A

S

S

I

V

G

G

L

L

G

G

C

C

P

P

F

F

S

A

P

P

G

G

A

A

T

K

G

G

N
|
N

V

V

A

D

T

T

E

V

D

A

V

V

L

E

L

M

L

L

N

H

S

E

M

M

G

G

H

F

D

E

T

T

G

G

I

L

D

D

binding calcium ion: D13 (= D12), H204 (= H203), H206 (= H205), N246 (= N245)

6ktqA Crystal structure of catalytic domain of homocitrate synthase from sulfolobus acidocaldarius (sahcs(dram)) in complex with alpha- ketoglutarate/zn2+/coa (see paper)
23% identity, 93% coverage: 1:284/307 of query aligns to 20:291/399 of 6ktqA

query
sites
6ktqA

M

M

K

K

V

V

R

G

V

I

N

L

D

D

V

S

G

T

P

L

R
|
R

D
x
E

G

G

L

E

Q

Q

S

T

Q

P

G

G

K

V

T

V

L

F

S

T

V

T

D

D

A

Q

R

R

A

V

Q

E

L

I

I

A

E

K

A

A

L

L

V

S

G

D

A

I

G

G

L

V

R

Q

N

M

I

I

E

E

A

A

G

G

S

H

F

-

V

-

S

-

P

P

K

A

A
x
V

V

S

P

P

Q

D

M

I

A

Y

G

E

T

G

D

I

E

R

L

R

F

I

S

I

R

K

L

L

P

K

A

R

S

E

D

G

K

V

V

I

R

K

Y

-

A

S

G

E

L

I

V

V

P

A

N

H

M

S

K
x
R

G
x
A

Y

V

Q

K

L

R

A

D

T

I

A

E

A

V

G

G

A

A

K

E

V

I

-

E

-

A

-

D

-

R

V

I

N

A

V

I

V
x
F

L

Y

S

G

V

I

T

S

D

D

T

T

M

H

N

L

Q

K

K

A

N

K

I
x
H

R

H

M

T

S

T

L

R

D

D

E

E

T

A

A

L

D

R

V

S

C

I

K

A

A

E

I

T

V

V

E

S

R

Y

G

A

H

K

L

S

E

H

G

G

V

V

E

K

V

V

Q
x
R

A

F

Y
x
T

L

A

A
x
E

V

D

A

A

F

T

E

R

C

A

P

D

F

Y

E

Q

G

Y

L

L

V

L

D

-

P

-

E

E

V

V

V

I

A

-

R

-

Y

-

A

-

R

K

L

T

M

V

H

R

S

D

A

A

G

G

A

A

A

D

K

R

I

V

I
x
S

I

I

A

A

D

D

T
|
T

I

V

G

G

A

V

A

L

N

Y

P

P

T

S

Q

R

V

T

R

R

Q

E

V

L

L

F

D

K

L

D

V

L

V

T

P

S

E

R

V

F

G

P

A

D

D

I

R

E

L

F

S

D

C

I

H
|
H

F

A

H
|
H

D

N

T

D

R

L

G

G

M

M

A

A

L

V

A

A

N

N

I

V

T

L

V

A

A

A

V

A

D

E

R

G

G

G

V

A

C

T

E

I

F

I

D

H

S

T

I

L

G

N

G

G

L

L

G

G

G

-

C

-

P

-

F

-

S

-

P

-

G

-

A

-

T

-

G

E

N

R

V

V

A

G

T

I

E

A

D

P

V

L

V

Q

L

V

L

A

N

A

S

A

M

L

G

K

H

Y

D

H

T

F

G

G

I

I

D

E

P

V

L

V

D

D

L

L

V

K

P

K

L

L

V

S

H

E

L

V

A

A

-

S

-

L

-

V

E

E

E

K

L

Y

T

S

G

G

V

I

P

A

L

L

binding 2-oxoglutaric acid: R30 (= R11), R154 (≠ Q135), T156 (≠ Y137), E158 (≠ A139), S184 (≠ I171), T188 (= T175), H216 (= H203), H218 (= H205)
binding coenzyme a: V67 (≠ A51), R96 (≠ K81), A97 (≠ G82), F116 (≠ V97), H128 (≠ I109), E158 (≠ A139)
binding zinc ion: E31 (≠ D12), H216 (= H203), H218 (= H205)

3ivtB Homocitrate synthase lys4 bound to 2-og (see paper)
26% identity, 73% coverage: 11:234/307 of query aligns to 38:250/400 of 3ivtB

query
sites
3ivtB

R
|
R

D
x
E

G

G

L

E

Q
|
Q

S

F

Q

A

G

N

K

A

T

F

L

F

S

D

V

T

D

E

A

K

R

K

A

I

Q

Q

L

I

I

A

E

K

A

A

L

L

V

D

G

N

A

F

G

G

L

V

R

D

N

Y

I

I

E

E

A

-

G

-

S

-

F

L

V

T

S

S

P

P

K

V

A

A

V

S

P

E

Q

Q

M

S

A

R

G

Q

T

D

D

C

E

E

L

A

F

I

S

C

R

K

L

L

P

G

A

L

S

K

D

C

K

K

V

I

R

-

Y

L

A

T

G
x
H

L

I

V

R

P

C

N

H

M

M

K

D

G

D

Y

A

Q

R

L

V

A

A

T

V

A

E

A

T

G

G

A

V

K

D

V

G

V

V

N

D

V

V

L

I

S

G

V

T

T

S

D

Q

T

Y

M

L

N

R

Q

K

K

Y

N

S

I

H

R

G

M

K

S

D

L

M

D

T

E

Y

T

I

A

I

D

D

V

S

C

A

K

T

A

E

I

V

V

I

E

N

R

F

G

V

H

K

L

S

E

K

G

G

V

I

E

E

V

V

Q
x
R

A

F

Y
x
S

L

S

A

E

V

D

A

S

F

F

E

R

C

-

P

-

F

-

E

S

G

D

L

L

V

V

D

D

P

-

E

-

V

L

A

S

R

L

Y

Y

A

-

R

K

L

A

M

V

H

D

S

K

A

I

G

G

A

V

A

N

K

R

I

V

I

G

I

I

A

A

D

D

T
|
T

I

V

G

G

A

C

A

A

N

T

P

P

T

R

Q

Q

V

V

R

Y

Q

D

V

L

L

I

D

R

L

T

V

L

V

R

P

G

E

V

V

V

G

S

A

C

D

D

R

-

L

I

S

E

C

C

H
|
H

F

F

H
|
H

D

N

T

D

R

T

G

G

M

M

A

A

L

I

A

A

N

N

I

A

T

Y

V

C

A

A

V

L

D

E

R

A

G

G

V

A

C

T

E

H

F

I

D

D

S

T

S

S

I

I

G

L

G

G

L

I

G

G

active site: Q42 (= Q15)
binding 2-oxoglutaric acid: R38 (= R11), H98 (≠ G75), R158 (≠ Q135), S160 (≠ Y137), T192 (= T175), H219 (= H203), H221 (= H205)
binding zinc ion: E39 (≠ D12), H219 (= H203), H221 (= H205)

Q9Y823 Homocitrate synthase, mitochondrial; HCS; EC 2.3.3.14 from Schizosaccharomyces pombe (strain 972 / ATCC 24843) (Fission yeast) (see 2 papers)
26% identity, 73% coverage: 11:234/307 of query aligns to 43:255/418 of Q9Y823

query
sites
Q9Y823

R
|
R

D
x
E

G

G

L

E

Q
|
Q

S

F

Q

A

G

N

K

A

T

F

L

F

S

D

V

T

D

E

A

K

R

K

A

I

Q

Q

L

I

I

A

E

K

A

A

L

L

V

D

G

N

A

F

G

G

L

V

R

D

N

Y

I

I

E
|
E

A

-

G

-

S

-

F

L

V

T

S

S

P

P

K

V

A

A

V

S

P

E

Q

Q

M

S

A

R

G

Q

T

D

D

C

E

E

L

A

F

I

S

C

R

K

L

L

P

G

A

L

S

K

D

C

K

K

V

I

R

-

Y

L

A

T

G
x
H

L

I

V

R

P

C

N

H

M

M

K

D

G

D

Y

A

Q

R

L

V

A

A

T

V

A

E

A

T

G

G

A

V

K

D

V

G

V

V

N
x
D

V

V

L

I

S

G

V

T

T

S

D

Q

T

Y

M

L

N

R

Q

K

K

Y

N

S

I

H

R

G

M

K

S

D

L

M

D

T

E

Y

T

I

A

I

D

D

V

S

C

A

K

T

A

E

I

V

V

I

E

N

R

F

G

V

H

K

L

S

E

K

G

G

V

I

E

E

V

V

Q
x
R

A

F

Y
x
S

L

S

A
x
E

V

D

A

S

F

F

E

R

C

-

P

-

F

-

E

S

G

D

L

L

V

V

D

D

P

-

E

-

V

L

A

S

R

L

Y

Y

A

-

R

K

L

A

M

V

H

D

S

K

A

I

G

G

A

V

A

N

K

R

I

V

I

G

I

I

A

A

D

D

T
|
T

I

V

G

G

A

C

A

A

N

T

P

P

T

R

Q

Q

V

V

R

Y

Q

D

V

L

L

I

D

R

L

T

V

L

V

R

P

G

E

V

V

V

G

S

A

C

D

D

R

-

L

I

S
x
E

C

C

H
|
H

F

F

H
|
H

D

N

T

D

R

T

G

G

M

M

A

A

L

I

A

A

N

N

I

A

T

Y

V

C

A

A

V

L

D

E

R

A

G

G

V

A

C

T

E

H

F

I

D

D

S

T

S

S

I

I

G

L

G

G

L

I

G

G

R43 (= R11) binding ; mutation R->A,K,Q: Abolishes the catalytic activity.
E44 (≠ D12) binding ; binding ; binding
Q47 (= Q15) mutation to A: Abolishes the catalytic activity.
E74 (= E42) 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 (≠ G75) binding ; mutation to A: Substantially impairs catalytic efficiency.
D123 (≠ N95) binding ; mutation to N: Does not affect the catalytic activity but impairs L-lysine inhibition.
R163 (≠ Q135) binding ; mutation R->A,Q: Abolishes the catalytic activity.; mutation to K: Severely diminishes affinity for 2-oxoglutarate and substantially impairs catalytic efficiency.
S165 (≠ Y137) binding ; mutation to A: Results in a moderate decrease in catalytic efficiency.
E167 (≠ A139) mutation E->A,Q: Abolishes the catalytic activity.
T197 (= T175) binding ; binding ; 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 (≠ S201) mutation to Q: Does not affect the catalytic activity but impairs L-lysine inhibition.
H224 (= H203) binding ; binding
H226 (= H205) binding ; binding

Sites not aligning to the query:

288 R→K: Does not affect the catalytic activity but impairs L-lysine inhibition.
332 Y→A: Abolishes the catalytic activity.; Y→F: Results in a decrease in catalytic efficiency.
364 Q→R: Does not affect the catalytic activity but impairs L-lysine inhibition.

3rmjB Crystal structure of truncated alpha-isopropylmalate synthase from neisseria meningitidis (see paper)
24% identity, 92% coverage: 2:284/307 of query aligns to 3:280/308 of 3rmjB

query
sites
3rmjB

K

R

V

V

R

I

V

I

N

F

D

D

V

T

G

T

P

L

R

R

D
|
D

G

G

L

E

Q
|
Q

S

S

Q

P

G

G

K

A

T

A

L

M

S

T

V

K

D

E

A

E

R

K

A

I

Q

R

L

V

I

A

E

R

A

Q

L

L

V

E

G

K

A

L

G

G

L

V

R

D

N

I

I

I

E

E

A

A

G

G

-

F

-

A

-

S

-

P

-

G

S

D

F

F

V

E

S

A

P

V

K

N

A

A

V

I

P

A

Q

K

M

T

A

I

G

T

T

K

D

S

E

T

L

V

F

C

S

S

R

L

L

S

P

R

A

A

S

I

D

E

K

R

-

D

V

I

R

R

Y

Q

A

A

G

G

L

-

V

-

P

-

N

-

M

-

K

-

G

-

Y

-

Q

E

L

A

A

V

T

A

A

P

A

A

G

P

A

K

K

K

V

R

V

I

N

H

V

T

V

F

L

I

S

A

V

T

T

S

D

P

T

I

M

H

N

M

Q

E

K

Y

N

K

I

L

R

K

M

M

S

K

L

P

D

K

E

Q

T

V

A

I

D

E

V

A

C

A

-

V

K

K

A

A

I

V

-

K

V

I

E

A

R

R

G

E

H

Y

L

T

E

D

G

D

V

V

E

E

V

F

Q

S

A

C

Y

E

L

D

A

A

V

L

A

R

F

S

E

E

C

I

P

D

F

F

E

-

G

-

L

-

V

-

D

-

P

-

E

-

V

-

V

L

A

A

R

E

Y

I

A

C

R

G

L

A

M

V

H

I

S

E

A

A

G

G

A

A

A

T

K

T

I

I

I

N

I

I

A

P

D

D

T

T

I

V

G

G

A

Y

A

S

N

I

P

P

T

Y

Q

K

V

T

R

E

Q

E

V

F

L

F

D

R

L

E

V

L

V

I

-

A

-

K

-

T

P

P

E

N

V

G

G

G

A

K

D

V

R

V

L

W

S

S

C

A

H
|
H

F

C

H
|
H

D

N

T

D

R

L

G

G

M

L

A

A

L

V

A

A

N

N

I

S

T

L

V

A

A

A

V

L

D

K

R

G

G

G

V

A

C

R

E

Q

F

V

D

E

S

C

S

T

I

V

G

N

G

G

L

L

G

G

G

-

C

-

P

-

F

-

S

-

P

-

G

E

A

R

T

A

G

G

N
|
N

V

A

A

S

T

V

E

E

D

E

V

I

V

V

L

M

L

A

L

L

-

K

-

V

-

R

-

H

N

D

S

L

M

F

G

G

H

L

D

E

T

T

G

G

I

I

D

D

P

T

L

T

D

Q

L

I

V

V

P

P

L

S

V

S

H

K

L

L

A

V

E

S

E

T

L

I

T

T

G

G

V

Y

P

P

L

V

active site: Q16 (= Q15)
binding manganese (ii) ion: D13 (= D12), H201 (= H203), H203 (= H205), N237 (= N245)

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, 92% coverage: 2:284/307 of query aligns to 6:283/517 of Q9JZG1

query
sites
Q9JZG1

K

R

V

V

R

I

V

I

N

F

D

D

V

T

G

T

P

L

R

R

D
|
D

G

G

L

E

Q

Q

S

S

Q

P

G

G

K

A

T

A

L

M

S

T

V

K

D

E

A

E

R

K

A

I

Q

R

L

V

I

A

E

R

A

Q

L

L

V

E

G

K

A

L

G

G

L

V

R

D

N

I

I

I

E

E

A

A

G

G

-

F

S

A

F

A

V

A

S

S

P

P

-

G

-

D

-

F

K

E

A

A

V

V

P

N

Q

A

M

I

A

A

G

K

T

T

D

I

E

T

L

K

-

S

-

T

-

V

-

C

-

S

F

L

S

S

R

R

L

A

P

I

A

E

S

R

D

D

K

-

V

I

R

R

Y

Q

A

A

G

G

L

-

V

-

P

-

N

-

M

-

K

-

G

-

Y

-

Q

E

L

A

A

V

T

A

A

P

A

A

G

P

A

K

K

K

V

R

V

I

N

H

V

T

V

F

L

I

S

A

V

T

T

S

D

P

T

I

M

H

N

M

Q

E

K

Y

N

K

I

L

R

K

M

M

S

K

L

P

D

K

E

Q

T

V

A

I

D

E

V

A

C

A

-

V

K

K

A

A

I

V

-

K

V

I

E

A

R

R

G

E

H

Y

L

T

E

D

G

D

V

V

E

E

V

F

Q

S

A

C

Y

E

L

D

A

A

V

L

A

R

F

S

E

E

C

I

P

D

F

F

E

-

G

-

L

-

V

-

D

-

P

-

E

-

V

-

V

L

A

A

R

E

Y

I

A

C

R

G

L

A

M

V

H

I

S

E

A

A

G

G

A

A

A

T

K

T

I

I

I

N

I

I

A

P

D

D

T

T

I

V

G

G

A

Y

A

S

N

I

P

P

T

Y

Q

K

V

T

R

E

Q

E

V

F

L

F

D

R

L

E

V

L

V

I

-

A

-

K

-

T

P

P

E

N

V

G

G

G

A

K

D

V

R

V

L

W

S

S

C

A

H
|
H

F

C

H
|
H

D

N

T

D

R

L

G

G

M

L

A

A

L

V

A

A

N

N

I

S

T

L

V

A

A

A

V

L

D

K

R

G

G

G

V

A

C

R

E

Q

F

V

D

E

S

C

S

T

I

V

G

N

G

G

L

L

G

G

G

-

C

-

P

-

F

-

S

-

P

-

G

E

A

R

T

A

G

G

N
|
N

V

A

A

S

T

V

E

E

D

E

V

I

V

V

L

M

L

A

L

L

-

K

-

V

-

R

-

H

N

D

S

L

M

F

G

G

H

L

D

E

T

T

G

G

I

I

D

D

P

T

L

T

D

Q

L

I

V

V

P

P

L

S

V

S

H

K

L

L

A

V

E

S

E

T

L

I

T

T

G

G

V

Y

P

P

L

V

D16 (= D12) binding
H204 (= H203) binding
H206 (= H205) binding
N240 (= N245) binding

Sites not aligning to the query:

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

3ivsA Homocitrate synthase lys4 (see paper)
28% identity, 73% coverage: 11:234/307 of query aligns to 20:219/364 of 3ivsA

query
sites
3ivsA

R

R

D
x
E

G

G

L

E

Q
|
Q

S

F

Q

A

G

N

K

A

T

F

L

F

S

D

V

T

D

E

A

K

R

K

A

I

Q

Q

L

I

I

A

E

K

A

A

L

L

V

D

G

N

A

F

G

G

L

V

R

D

N

Y

I

I

E

E

A

-

G

-

S

-

F

L

V

T

S

S

P

P

K

V

A

A

V

S

P

E

Q

Q

M

S

A

R

G

Q

T

D

D

C

E

E

L

A

F

I

S

C

R

K

L

L

P

G

A

L

S

K

D

C

K

K

V

I

R

-

Y

L

A

T

G

H

L

I

V

R

P

C

N

H

M

M

K

D

G

D

Y

A

Q

R

L

V

A

A

T

V

A

E

A

T

G

G

A

V

K

D

V

G

V

V

N

D

V

V

L

I

S

G

V

T

T

T

D

Y

T

I

M

I

N

D

Q

-

K

-

N

-

I

-

R

-

M

-

S

S

L

A

D

T

E

E

T

V

A

I

D

N

V

F

C

V

K

K

A

S

I

-

V

-

E

-

R

-

G

-

H

-

L

-

E

K

G

G

V

I

E

E

V

V

Q

R

A

F

Y

S

L

S

A

E

V

D

A

S

F

F

E

R

C

-

P

-

F

-

E

S

G

D

L

L

V

V

D

D

P

-

E

-

V

L

A

S

R

L

Y

Y

A

-

R

K

L

A

M

V

H

D

S

K

A

I

G

G

A

V

A

N

K

R

I

V

I

G

I

I

A

A

D

D

T

T

I

V

G

G

A

C

A

A

N

T

P

P

T

R

Q

Q

V

V

R

Y

Q

D

V

L

L

I

D

R

L

T

V

L

V

R

P

G

E

V

V

V

G

S

A

C

D

D

R

-

L

I

S

E

C

C

H
|
H

F

F

H
|
H

D

N

T

D

R

T

G

G

M

M

A

A

L

I

A

A

N

N

I

A

T

Y

V

C

A

A

V

L

D

E

R

A

G

G

V

A

C

T

E

H

F

I

D

D

S

T

S

S

I

I

G

L

G

G

L

I

G

G

active site: Q24 (= Q15)
binding cobalt (ii) ion: E21 (≠ D12), H188 (= H203), H190 (= H205)

4jn6C Crystal structure of the aldolase-dehydrogenase complex from mycobacterium tuberculosis hrv37 (see paper)
25% identity, 87% coverage: 3:269/307 of query aligns to 4:255/339 of 4jn6C

query
sites
4jn6C

V

V

R

R

V

I

N

T

D

D

V

T

G

S

P

L

R
|
R

D
|
D

G

G

L

S

Q
x
H

S

H

Q

K

G

R

K

H

T

Q

L

F

S

T

V

K

D

D

A

E

R

V

A

G

Q

A

L

I

I

V

E

A

A

A

L

L

V

D

G

A

A

A

G

G

L

V

R

P

N

V

I

I

E

E

A

-

G

-

S

-

F

-

V

V

S

T

P

H

K

G

A

D

V

G

P

L

Q

G

M

G

A

S

G

S

T

F

D

N

E

Y

L

G

F

F

S

S

R

K

L

T

P

P

A

E

S

Q

D

E

K

L

V

I

R

K

Y

L

A

A

G

A

L

-

V

-

P

-

N

-

M

-

K

-

G

-

Y

-

Q

-

L

-

A

A

T

T

A

A

A

K

G

E

A

A

K

R

V

I

V

A

N

F

V

L

V

M

L

L

S

P

V

G

T

V

D

G

T

T

M

-

N

-

Q

K

K

D

N

D

I

I

R

K

M

E

S

A

L

R

D

D

E

N

T

G

A

G

D

S

V

I

C

C

K

R

A

-

I

I

V

A

E

T

R

H

G

C

H

T

L

E

E

A

G

D

V

V

E

S

V

I

Q

Q

A

-

Y

H

L

F

A

G

V

L

A

A

F

R

E

E

C

L

P

G

F

L

E

E

G

T

L

V

-

G

-

F

-

L

-
x
M

-

M

-

A

-

H

-

T

V

I

D

A

P

P

E

E

V

K

V

L

A

A

R

A

Y

Q

A

A

R

R

L

I

M

M

H

A

S

D

A

A

G

G

A

C

A

Q

K

C

I

V

I

Y

I

V

A
x
V

D

D

T
x
S

I

A

G

G

A

A

A

L

N

V

P

L

T

D

Q

G

V

V

R

A

Q

D

V

R

L

V

D

S

L

A

V

L

V

V

P

A

E

E

V

L

G

G

A

E

D

D

-

A

R

Q

L

V

S

G

C

F

H
|
H

F

G

H
|
H

D

E

T

N

R

L

G

G

M

L

A

G

L

V

A

A

N

N

I

S

T

V

V

A

A

A

V

V

D

R

R

A

G

G

V

A

C

K

E

Q

F

I

D

D

S

-

I

-

G

-

L

-

G

G

G

S

C

C

P

R

F

R

S

F

P

G

G

A

A

G

T

A

G

G

N

N

V

A

A

P

T

V

E

E

D

A

V

L

V

I

L

G

L

V

L

F

N

D

S

K

M

I

G

G

H

V

D

K

T

T

G

G

I

I

D

D

P

F

L

F

D

D

L

I

active site: D13 (= D12), H16 (≠ Q15), H195 (= H203), H197 (= H205)
binding manganese (ii) ion: D13 (= D12), H195 (= H203), H197 (= H205)
binding oxalate ion: R12 (= R11), M136 (vs. gap), V164 (≠ A173), S166 (≠ T175), H195 (= H203), H197 (= H205)

Sites not aligning to the query:

active site: 286
binding oxalate ion: 286

3mi3A Homocitrate synthase lys4 bound to lysine (see paper)
28% identity, 73% coverage: 11:234/307 of query aligns to 20:221/370 of 3mi3A

query
sites
3mi3A

R
|
R

D
x
E

G

G

L

E

Q
|
Q

S

F

Q

A

G

N

K

A

T

F

L

F

S

D

V

T

D

E

A

K

R

K

A

I

Q

Q

L

I

I

A

E

K

A

A

L

L

V

D

G

N

A

F

G

G

L

V

R

D

N

Y

I

I

E

E

A

-

G

-

S

-

F

L

V

T

S

S

P

P

K

V

A

A

V

S

P

E

Q

Q

M

S

A

R

G

Q

T

D

D

C

E

E

L

A

F

I

S

C

R

K

L

L

P

G

A

L

S

K

D

C

K

K

V

I

R

-

Y

L

A

T

G

H

L

I

V

R

P

C

N

H

M

M

K

D

G

D

Y

A

Q

R

L

V

A

A

T

V

A

E

A

T

G

G

A

V

K

D

V

G

V

V

N
x
D

V

V

L

I

S

G

V

T

T

S

D

M

T

T

M

Y

N

-

Q

-

K

-

N

-

I

I

R

I

M

D

S

S

L

A

D

T

E

E

T

V

A

I

D

N

V

F

C

V

K

K

A

S

I

-

V

-

E

-

R

-

G

-

H

-

L

-

E

K

G

G

V

I

E

E

V

V

Q

R

A

F

Y

S

L

S

A

E

V

D

A

S

F

F

E

R

C

-

P

-

F

-

E

S

G

D

L

L

V

V

D

D

P

-

E

-

V

L

A

S

R

L

Y

Y

A

-

R

K

L

A

M

V

H

D

S

K

A

I

G

G

A

V

A

N

K

R

I

V

I

G

I

I

A

A

D

D

T
|
T

I

V

G

G

A

C

A

A

N

T

P

P

T

R

Q

Q

V

V

R

Y

Q

D

V

L

L

I

D

R

L

T

V

L

V

R

P

G

E

V

V

V

G

S

A

C

D

D

R

-

L

I

S

E

C

C

H
|
H

F

F

H
|
H

D

N

T

D

R

T

G

G

M

M

A

A

L

I

A

A

N

N

I

A

T

Y

V

C

A

A

V

L

D

E

R

A

G

G

V

A

C

T

E

H

F

I

D

D

S

T

S

S

I

I

G

L

G

G

L

I

G

G

active site: Q24 (= Q15)
binding lysine: R20 (= R11), D100 (≠ N95), T163 (= T175), H190 (= H203), H192 (= H205)
binding zinc ion: E21 (≠ D12), H190 (= H203), H192 (= H205)

P9WMK5 4-hydroxy-2-oxohexanoate aldolase; 4-hydroxy-2-keto-pentanoic acid aldolase; 4-hydroxy-2-oxopentanoate aldolase; 4-hydroxy-2-oxovalerate aldolase; HOA; EC 4.1.3.43; EC 4.1.3.39 from Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv) (see paper)
25% identity, 87% coverage: 3:269/307 of query aligns to 7:258/346 of P9WMK5

query
sites
P9WMK5

V

V

R

R

V

I

N

T

D

D

V

T

G

S

P

L

R

R

D
|
D

G

G

L

S

Q

H

S

H

Q

K

G

R

K

H

T

Q

L

F

S

T

V

K

D

D

A

E

R

V

A

G

Q

A

L

I

I

V

E

A

A

A

L

L

V

D

G

A

A

A

G

G

L

V

R

P

N

V

I

I

E

E

A

-

G

-

S

-

F

-

V

V

S

T

P

H

K

G

A

D

V

G

P

L

Q

G

M

G

A

S

G

S

T

F

D

N

E

Y

L

G

F

F

S

S

R

K

L

T

P

P

A

E

S

Q

D

E

K

L

V

I

R

K

Y

L

A

A

G

A

L

-

V

-

P

-

N

-

M

-

K

-

G

-

Y

-

Q

-

L

-

A

A

T

T

A

A

A

K

G

E

A

A

K

R

V

I

V

A

N

F

V

L

V

M

L

L

S

P

V

G

T

V

D

G

T

T

M

-

N

-

Q

K

K

D

N

D

I

I

R

K

M

E

S

A

L

R

D

D

E

N

T

G

A

G

D

S

V

I

C

C

K

R

A

-

I

I

V

A

E

T

R

H

G

C

H

T

L

E

E

A

G

D

V

V

E

S

V

I

Q

Q

A

-

Y

H

L

F

A

G

V

L

A

A

F

R

E

E

C

L

P

G

F

L

E

E

G

T

L

V

-

G

-

F

-

L

-

M

-

A

-

H

-

T

V

I

D

A

P

P

E

E

V

K

V

L

A

A

R

A

Y

Q

A

A

R

R

L

I

M

M

H

A

S

D

A

A

G

G

A

C

A

Q

K

C

I

V

I

Y

I

V

A

V

D

D

T

S

I

A

G

G

A

A

A

L

N

V

P

L

T

D

Q

G

V

V

R

A

Q

D

V

R

L

V

D

S

L

A

V

L

V

V

P

A

E

E

V

L

G

G

A

E

D

D

-

A

R

Q

L

V

S

G

C

F

H
|
H

F

G

H
|
H

D

E

T

N

R

L

G

G

M

L

A

G

L

V

A

A

N

N

I

S

T

V

V

A

A

A

V

V

D

R

R

A

G

G

V

A

C

K

E

Q

F

I

D

D

S

-

I

-

G

-

L

-

G

G

G

S

C

C

P

R

F

R

S

F

P

G

G

A

A

G

T

A

G

G

N

N

V

A

A

P

T

V

E

E

D

A

V

L

V

I

L

G

L

V

L

F

N

D

S

K

M

I

G

G

H

V

D

K

T

T

G

G

I

I

D

D

P

F

L

F

D

D

L

I

D16 (= D12) binding
H198 (= H203) binding
H200 (= H205) binding

Sites not aligning to the query:

322 G→F: Abolishes substrate channeling to HsaG.

3bliA Crystal structure of the catalytic domain of licms in complexed with pyruvate and acetyl-coa (see paper)
20% identity, 91% coverage: 2:281/307 of query aligns to 1:274/311 of 3bliA

query
sites
3bliA

K

R

V

L

R

E

V

I

N

L

D

D

V

V

G

T

P

L

R
|
R

D
|
D

G

G

L

E

Q
|
Q

S

T

Q

R

G

G

K

V

T

S

L

F

S

S

V

T

D

S

A

E

R

K

A

L

Q

N

L

I

I

A

E

K

A

F

L

L

-

L

-

Q

-

K

-

L

-

N

-

V

-

D

-

R

V

V

G

E

A

I

G

A

L

S

R

A

N
x
R

I
x
V

E

S

A

K

G

G

S

E

F

L

V

E

S

T

P

V

K

Q

A

K

V

I

P

M

Q

E

M

W

A

A

G

A

T

T

D

E

E

Q

L

L

F

-

S

-

R

-

L

-

P

-

A

-

S

T

D

E

K

R

V

I

R

E

Y

I

A

L

G

G

L

F

V

V

P

D

N

G

M

N

K

K

G

T

Y

V

Q

D

L

W

A

I

T

K

A

D

A

S

G

G

A

A

K

K

V

V

V

L

N

N

V

L

L

T

S

K

V

G

T

S

D

L

T

H

M

H

N

L

Q

E

K

K

N

Q

I

L

R

G

M

K

S

T

L

P

D

K

E

E

T

F

A

F

D

T

V

D

C

V

K

S

A

F

I

V

V

I

E

E

R

Y

G

A

H

I

L

K

E

S

G

G

V

L

E

K

V

I

Q

N

A

V

Y
|
Y

L

L

A
x
E

V

-

A

D

F

W

E

S

C

N

P

G

F

F

E

R

G

N

L

-

V

-

D

S

P

P

E

D

V

Y

V

V

A

K

R

S

Y

L

A

V

R

E

L

H

M

L

H

S

S

K

A

E

G

H

A

I

A

E

K

R

I

I

I

F

I

L

A
x
P

D

D

T
|
T

I

L

G

G

A

V

A

L

N

S

P

P

T

E

Q

E

V

T

R

F

Q

Q

V

G

L

V

D

D

L

S

V

L

V

I

P

Q

E

K

V

Y

G

P

A

D

D

I

R

H

L

F

S

E

C

F

H
|
H

F

G

H
|
H

D

N

T

D

R

Y

G

D

M

L

A

S

L

V

A

A

N

N

I

S

T

L

V

Q

A

A

V

I

D

R

R

A

G

G

V

V

C

K

E

G

F

L

D

H

S

A

S

S

I

I

G

N

G

G

L

L

G

G

G

-

C

-

P

-

F

-

S

-

P

-

G

E

A

R

T

A

G

G

N

N

V

T

A

P

T

L

E

E

D

A

V

L

V

V

L

T

L

I

N

H

S

D

M

K

G

S

H

N

D

S

-

K

T

T

G

N

I

I

D

N

P

E

L

I

D

A

L

I

V

T

P

E

L

A

V

S

H

R

L

L

A

V

E

E

E

V

L

F

T

S

G

G

active site: Q14 (= Q15)
binding acetyl coenzyme *a: Q14 (= Q15), R47 (≠ N40), V48 (≠ I41), E140 (≠ A139)
binding pyruvic acid: R10 (= R11), Y138 (= Y137), P171 (≠ A173), T173 (= T175)
binding zinc ion: D11 (= D12), H201 (= H203), H203 (= H205)

Q8F3Q1 (R)-citramalate synthase CimA; LiCMS; EC 2.3.3.21 from Leptospira interrogans serogroup Icterohaemorrhagiae serovar Lai (strain 56601) (see 2 papers)
20% identity, 91% coverage: 2:281/307 of query aligns to 7:280/516 of Q8F3Q1

query
sites
Q8F3Q1

K

R

V

L

R

E

V

I

N

L

D

D

V

V

G

T

P

L

R
|
R

D
|
D

G

G

L

E

Q

Q

S

T

Q

R

G

G

K

V

T

S

L

F

S

S

V

T

D

S

A

E

R

K

A

L

Q

N

L

I

I

A

E

K

A

F

L

L

-

L

-

Q

-

K

-

L

-

N

-

V

-

D

-

R

V

V

G

E

A

I

G

A

L

S

R

A

N

R

I

V

E

S

A

K

G

G

S

E

F

L

V

E

S

T

P

V

K

Q

A

K

V

I

P

M

Q

E

M

W

A

A

G

A

T

T

D

E

E

Q

L

L

F

-

S

-

R

-

L

-

P

-

A

-

S

T

D

E

K

R

V

I

R

E

Y

I

A
x
L

G

G

L
x
F

V

V

P

D

N

G

M

N

K

K

G

T

Y

V

Q

D

L

W

A

I

T

K

A

D

A

S

G

G

A

A

K

K

V

V

V

L

N

N

V

L

V
x
L

L

T

S

K

V

G

T

S

D

L

T

H

M

H

N

L

Q

E

K

K

N

Q

I

L

R

G

M

K

S

T

L

P

D

K

E

E

T

F

A

F

D

T

V

D

C

V

K

S

A

F

I

V

V

I

E

E

R

Y

G

A

H

I

L

K

E

S

G

G

V

L

E

K

V

I

Q

N

A

V

Y
|
Y

L

L

A
x
E

V

-

A

D

F

W

E

S

C

N

P

G

F

F

E

R

G

N

L

-

V

-

D

S

P

P

E

D

V

Y

V

V

A

K

R

S

Y

L

A

V

R

E

L

H

M

L

H

S

S

K

A

E

G

H

A

I

A

E

K

R

I

I

I

F

I

L

A

P

D

D

T
|
T

I

L

G

G

A

V

A

L

N

S

P

P

T

E

Q

E

V

T

R

F

Q

Q

V

G

L

V

D

D

L

S

V

L

V

I

P

Q

E

K

V

Y

G

P

A

D

D

I

R

H

L

F

S

E

C

F

H

H

F

G

H

H

D

N

T

D

R

Y

G

D

M

L

A

S

L

V

A

A

N

N

I

S

T

L

V

Q

A

A

V

I

D

R

R

A

G

G

V

V

C

K

E

G

F

L

D

H

S

A

S

S

I

I

G

N

G

G

L

L

G

G

G

-

C

-

P

-

F

-

S

-

P

-

G

E

A

R

T

A

G

G

N

N

V

T

A

P

T

L

E

E

D

A

V

L

V

V

L

T

L

I

N

H

S

D

M

K

G

S

H

N

D

S

-

K

T

T

G

N

I

I

D

N

P

E

L

I

D

A

L

I

V

T

P

E

L

A

V

S

H

R

L

L

A

V

E

E

E

V

L

F

T

S

G

G

R16 (= R11) mutation R->K,Q: Loss of activity.
RD 16:17 (= RD 11:12) binding
D17 (= D12) 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 (≠ A74) 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 (≠ L76) mutation to A: 5-fold increase in Km for acetyl-CoA and 120-fold decrease in kcat.
L104 (≠ V97) mutation to V: 1.8-fold increase in Km for pyruvate and 3.4-fold decrease in kcat.
Y144 (= Y137) binding ; 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 (≠ A139) mutation E->D,Q: Minor effects on the binding of acetyl-CoA, but causes a strong decrease in kcat.
T179 (= T175) binding ; mutation to A: 16.4-fold increase in Km for pyruvate and 186-fold decrease in kcat.

Sites not aligning to the query:

302 mutation H->A,N: Loss of activity.
304 D→A: 5.2-fold increase in Km for acetyl-CoA and 16.6-fold decrease in kcat.
310 N→A: 2.2-fold increase in Km for acetyl-CoA and 1.7-fold decrease in kcat.
311 L→A: 8-fold increase in Km for acetyl-CoA and 6-fold decrease in kcat.
312 Y→A: Loss of activity.
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.

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)
23% identity, 88% coverage: 5:275/307 of query aligns to 13:275/347 of Q53WI0

query
sites
Q53WI0

V

V

N

V

D

D

V

T

G

T

P

L

R

R

D

D

G

G

L

S

Q

H

S

A

Q

H

G

R

K

H

T

Q

L

Y

S

T

V

V

D

E

A

E

R

A

A

R

Q

A

L

I

I

A

E

Q

A

A

L

L

V

D

G

E

A

A

G

G

L

V

R

Y

N

A

I

I

E

E

A

V

-

S

-

H

G

G

S

D

F

G

V

L

S

G

P

G

K

S

A

S

V

L

P

Q

Q

Y

-

G

M

F

A

S

G

R

T

T

D

D

E

E

L

M

F

E

S

L

R

I

L

R

P

A

A

V

S

R

D

E

K

T

V

V

R

R

Y

R

A

A

G

K

-

V

-

A

-

L

L

L

V

L

P

P

N

G

M

I

-

G

-

T

-

R

K

K

G

E

Y

L

Q

K

L

E

A

A

T

V

A

E

A

A

G

G

A

I

K

Q

V

M

V

V

N

R

V

I

V

A

L

T

S

Q

V

C

T

T

D

E

T

-

M

-

N

-

Q

-

K

-

N

-

I

-

R

-

M

-

S

-

L

-

D

-

E

-

T

-

A

A

D

D

V

I

C

S

K

E

A

Q

I

H

V

F

E

G

R

M

G

A

H

K

L

E

E

M

G

G

V

L

E

E

V

A

Q

V

A

G

Y

F

L

L

A

M

V

M

A

S

F

H

E

M

C

R

P

P

F

-

E

-

G

-

L

-

V

-

D

-

P

P

E

E

V

F

V

L

A

A

R

E

Y

Q

A

A

R

R

L

L

M

M

H

E

S

G

A

Y

G

G

A

A

A

D

K

V

I

V

I

Y

I

I

A

V

D

D

T

S

I

A

G

G

A

A

A

M

N

L

P

P

T

E

Q

D

V

A

R

Y

Q

A

V

R

L

V

D

K

L

A

V

L

V

K

P

E

E

A

V

L

G

S

A

R

D

A

R

K

L

V

S

G

C

F

H

H

F

A

H

H

D

N

T

N

R

L

G

G

M

L

A

A

L

I

A

G

N

N

I

T

T

L

V

A

A

A

V

L

D

A

R

A

G

G

V

A

C

D

E

W

F

V

D

D

S

A

S

T

I

L

G

R

G

G

L

Y

G

G

G

-

C

-

P

-

F

-

S

-

P

-

G

A

A

G

T

A

G

G

N

N

V

A

A

P

T

L

E

E

D

V

V

L

V

A

L

A

L

V

L

L

N

D

S

K

M

A

G

G

H

L

D

N

T

P

G

G

I

L

D

D

P

V

L

F

D

K

L

L

V

L

-

D

-

A

-

E

-

Y

-

V

-

M

-

G

P

P

L

I

V

L

H

H

L

F

Sites not aligning to the query:

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

Query Sequence

>GFF2664 FitnessBrowser__Marino:GFF2664
MKVRVNDVGPRDGLQSQGKTLSVDARAQLIEALVGAGLRNIEAGSFVSPKAVPQMAGTDE
LFSRLPASDKVRYAGLVPNMKGYQLATAAGAKVVNVVLSVTDTMNQKNIRMSLDETADVC
KAIVERGHLEGVEVQAYLAVAFECPFEGLVDPEVVARYARLMHSAGAAKIIIADTIGAAN
PTQVRQVLDLVVPEVGADRLSCHFHDTRGMALANITVAVDRGVCEFDSSIGGLGGCPFSP
GATGNVATEDVVLLLNSMGHDTGIDPLDLVPLVHLAEELTGVPLGGKSFRWLSQQRAKLL
GEAGHVG

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