SitesBLAST

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)
51% identity, 95% coverage: 5:278/287 of query aligns to 78:351/370 of Q8TB92

query
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Q8TB92

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R86 (= R13) mutation to Q: Abolishes catalytic activity.
L237 (= L164) mutation to S: Abolishes catalytic activity.
H278 (= H205) 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.

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)
52% identity, 97% coverage: 1:278/287 of query aligns to 29:306/325 of P35914

query
sites
P35914

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E37 (= E9) to K: in HMGCLD; activity lower than 5% respect to the wild-type; mutation to D: Normal activity.
R41 (= R13) to Q: in HMGCLD; loss of activity and of proton exchange; dbSNP:rs121964997; mutation to M: Reduced activity, and loss of proton exchange.
D42 (= D14) 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 (= K20) to N: in HMGCLD; abolishes almost all enzymatic activity
E72 (= E44) mutation to A: Loss of activity, and reduced affinity for metal cofactor and substrate.
S142 (= S114) to F: in HMGCLD; activity lower than 5% respect to the wild-type
C174 (= C146) to Y: in HMGCLD; activity lower than 5% respect to the wild-type; dbSNP:rs765475941
F192 (≠ L164) to S: in HMGCLD; activity lower than 5% respect to the wild-type
I200 (≠ V172) to F: in HMGCLD; activity lower than 5% respect to the wild-type
G203 (= G175) to E: in HMGCLD; complete loss of activity; dbSNP:rs1553131940
D204 (= D176) mutation to A: Reduced activity, and reduced affinity for metal cofactor and substrate.
H233 (= H205) to R: in HMGCLD; loss of activity; dbSNP:rs727503963; mutation to A: Loss of activity, and reduced proton exchange rate.
E279 (≠ L251) mutation to A: Reduced thermal stability, but normal activity.
D280 (≠ S252) 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)
52% identity, 97% coverage: 1:278/287 of query aligns to 2:279/296 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 (= R13), D15 (= D14), Q18 (= Q17), F49 (= F48), V50 (= V49), S51 (= S50), W54 (= W53), P81 (= P80), N82 (= N81), K84 (= K83), G85 (= G84), N111 (= N110), R122 (= R121), Y140 (= Y139), S142 (= S141), T178 (= T177), H206 (= H205)
binding magnesium ion: D15 (= D14), H206 (= H205), H208 (= H207)

2cw6A Crystal structure of human hmg-coa lyase: insights into catalysis and the molecular basis for hydroxymethylglutaric aciduria (see paper)
52% identity, 97% coverage: 1:278/287 of query aligns to 2:279/296 of 2cw6A

query
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2cw6A

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binding 3-hydroxypentanedioic acid: Q18 (= Q17), F100 (= F99)
binding magnesium ion: D15 (= D14), H206 (= H205), H208 (= H207), N248 (= N247)

3mp5B Crystal structure of human lyase r41m in complex with hmg-coa (see paper)
51% identity, 97% coverage: 1:278/287 of query aligns to 2:279/296 of 3mp5B

query
sites
3mp5B

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D
|
D

G

G

L

L

Q
|
Q

N

N

E

E

K

K

T

N

L

I

I

V

P

S

T

T

A

P

Q

V

K

K

I

I

E

K

L

L

I

I

N

D

R

M

L

L

S

S

E

E

C

A

G

G

F

L

K

S

K

V

I

I

E

E

T

T

S

T

S

S

F

F

V

V

S
|
S

P

P

K

K

W
|
W

V

V

P

P

Q

Q

M

M

A

G

D

D

A

H

S

T

Q

E

V

V

F

L

E

K

G

G

I

I

T

Q

R

K

K

F

A

P

G

G

I

I

R

N

Y

Y

T

P

A

V

L

L

T

T

P

P

N

N

I

L

K

K

G

G

Y

F

E

E

R

A

A

A

K

V

Q

A

A

A

G

G

A

A

D

K

E

E

V

V

A

V

I

I

F
|
F

A

G

S

A

A

A

S

S

E

E

G

L

F

F

S

T

Q

K

K

K

N
|
N

I

I

N
|
N

C

C

S

S

I

I

E

E

S

S

F

F

E

Q

R

R

F

F

A

D

P

A

I

I

L

L

E

K

T

A

A

A

K

Q

A

S

D

A

S

N

I

I

P

S

V

V

R

R

G

G

Y
|
Y

V

V

S
|
S

C

C

V

A

V

L

E

G

C

C

P

P

Y

Y

D

E

G

G

P

K

T

I

P

S

V

P

Q

A

N

K

T

V

A

A

K

E

V

V

S

T

E

K

R

K

L

F

L

Y

Q

S

M

M

G

G

C

C

Y

Y

E

E

V

I

S

S

L

L

G

G

D

D

T
|
T

I

I

G

G

A

V

A

G

I

T

P

P

E

G

T

I

T

M

E

K

A

D

M

M

L

L

D

S

A

A

L

V

L

M

K

Q

V

E

V

V

P

P

A

L

E

A

K

A

L

L

A

A

G

V

H
|
H

F

C

H
|
H

D

D

T

T

H

Y

D

G

F

Q

A

A

L

L

A

A

N

N

I

T

M

L

S

M

S

A

I

L

K

Q

M

M

G

G

L

V

R

S

T

V

F

V

D

D

T

S

A

S

I

V

G

A

G

G

L

L

G

G

C
|
C

P

P

Y

Y

A

A

P

Q

G

G

A

A

K

S

G

G

N

N

V

L

S

A

T

T

L

E

S

D

V

L

A

V

K

Y

M

M

A

L

K

E

L

G

L

L

D

G

Y

I

D

H

T

T

N

G

L

V

D

N

I

L

E

Q

K

K

L

L

E

L

Q

E

T

A

Q

G

D

N

F

F

I

I

binding 3-hydroxy-3-methylglutaryl-coenzyme a: D15 (= D14), Q18 (= Q17), S51 (= S50), W54 (= W53), F100 (= F99), N111 (= N110), N113 (= N112), Y140 (= Y139), S142 (= S141), T178 (= T177), C239 (= C238)
binding magnesium ion: D15 (= D14), H206 (= H205), H208 (= H207)

P13703 Hydroxymethylglutaryl-CoA lyase; HL; HMG-CoA lyase; 3-hydroxy-3-methylglutarate-CoA lyase; EC 4.1.3.4 from Pseudomonas mevalonii (see paper)
50% identity, 94% coverage: 5:274/287 of query aligns to 4:273/301 of P13703

query
sites
P13703

L

V

T

K

I

V

F

F

E

E

M

V

G

G

P

P

R

R

D

D

G

G

L

L

Q

Q

N

N

E

E

K

R

T

Q

L

P

I

L

P

S

T

V

A

A

Q

A

K

R

I

V

E

G

L

L

I

I

N

G

R

E

L

L

S

A

E

G

C

T

G

G

F

L

K

R

K

H

I

I

E

E

T

A

S

G

S

A

F

F

V

V

S

S

P

P

K

R

W

W

V

V

P

P

Q

Q

M

M

A

A

D

G

A

S

S

D

Q

E

V

V

F

L

E

R

G

Q

I

L

T

P

R

S

K

N

A

D

G

G

I

V

R

S

Y

Y

T

T

A

A

L

L

T

V

P

P

N

N

I

R

K

Q

G

G

Y

F

E

E

R

A

A

A

K

Q

Q

R

A

A

G

G

A

C

D

R

E

E

V

V

A

A

I

V

F

F

A

A

S

A

A

A

S

S

E

E

G

A

F

F

S

S

Q

R

K

N

N

N

I

I

N

N

C

C

S

S

I

I

E

D

E

E

S

S

F

F

E

E

R

R

F

F

A

T

P

P

I

V

L

L

E

R

T

A

A

A

K

N

A

E

D

A

S

S

I

I

P

R

V

V

R

R

G

G

Y

Y

V

V

S

S

C

C

V

V

V

L

E

G

C

C

P

P

Y

F

D

S

G

G

P

A

T

V

P

A

V

P

Q

E

N

A

T

V

A

A

K

K

V

V

S

A

E

R

R

R

L

L

L

Y

Q

E

M

L

G

G

C

C

Y

Y

E

E

V

I

S

S

L

L

G

G

D

D

T

T

I

I

G

G

A

A

A

G

I

R

P

P

E

D

T

E

T

T

E

A

A

Q

M

L

L

F

D

E

A

L

L

C

L

A

K

R

V

Q

V

L

P

P

A

V

E

A

K

A

L

L

A

A

G

G

H

H

F

F

H

H

D

D

T

T

H

W

D

G

F

M

A

A

L

I

A

A

N

N

I

V

M

H

S

A

I

L

K

A

M

Q

G

G

L

V

R

R

T

T

F

F

D

D

T

S

A

S

I

V

G

A

G

G

L

L

G

G

C
|
C

P

P

Y

Y

A

S

P

P

G

G

A

A

K

S

G

G

N

N

V

V

S

A

T

T

L

E

S

D

V

L

A

L

K

Y

M

L

A

L

K

H

L

G

L

L

D

G

Y

Y

D

S

T

T

N

G

L

V

D

D

I

L

E

E

K

A

L

V

E

A

Q

Q

T

V

C237 (= C238) active site

6ndsA Structure of an hmg-coa lyase from acenitobacter baumannii in complex with coenzyme a and 3-methylmalate
39% identity, 95% coverage: 1:273/287 of query aligns to 4:275/305 of 6ndsA

query
sites
6ndsA

M

F

S

S

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D

R

L

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I

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F

Q

E

E

M

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D
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D

G

G

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L

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Q

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L

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I

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T

A

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K

I

I

E

D

L

L

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I

N

N

R

Q

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L

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M

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G

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F

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F

F

V
|
V

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|
S

P

P

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W

A

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x
I

P

P

Q

N

M

L

A

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D

A

G

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E

Q

E

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V

F

F

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G

I

I

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R

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H

A

K

G

D

I

I

R

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Y

Y

T

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A

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L

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P

P

N
|
N

I

L

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K

G
|
G

Y

A

E

L

R
|
R

A

A

K

V

Q

E

A

A

G

N

A

A

D

N

E

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L

A

N

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L

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L

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S

A

A

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S

N

Q

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A

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|
N

I
x
M

N
x
R

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M

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I

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E

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A

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-

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Y

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E

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L

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H

L

V

L

L

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S

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L

V

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S

A

P

E

E

K

Q

L

L

A

T

G

L

H
|
H

F

F

H
|
H

D

N

T

T

H

R

D

G

F

L

A

G

L

L

A

T

N

N

I

V

M

L

S

A

I

Y

K

E

M

V

G

G

L

A

R

R

T

R

F

F

D

D

T

A

A

A

I

L

G

G

L

L

G

G

C

C

P

P

Y

F

A

A

P

P

G

G

A

A

K

S

G

G

N

N

V

I

S

C

T

T

L

E

S

D

V

L

A

V

K

N

M

M

A

C

K

E

L

E

L

I

D

G

Y

I

D

P

T

T

N

T

L

I

D

D

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L

E

D

K

A

L

L

E

I

Q

Q

binding coenzyme a: V52 (= V49), S53 (= S50), I57 (≠ V54), N84 (= N81), G87 (= G84), R90 (= R87), N113 (= N110), M114 (≠ I111), R115 (≠ N112)
binding zinc ion: D17 (= D14), H207 (= H205), H209 (= H207)

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, 82% coverage: 1:236/287 of query aligns to 18:247/399 of 6ktqA

query
sites
6ktqA

M

L

S

H

K

M

R

K

L

V

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G

I

I

F

L

E

D

M

S

G

T

P

L

R
|
R

D
x
E

G

G

L

E

Q

Q

N

T

E

P

K

G

T

V

L

V

I

F

P

T

T

T

A

D

Q

Q

K

R

I

V

E

E

L

I

I

A

N

K

R

A

L

L

S

S

E

D

C

I

G

G

F

V

K

Q

K

M

I

I

E

E

T

A

S

G

S

H

-

P

F

A

V
|
V

S

S

P

P

K

-

W

-

V

-

P

-

Q

-

M

-

A

-

D

-

A

-

S

-

Q

D

V

I

F

Y

E

E

G

G

I

I

T

R

R

R

-

I

-

K

-

L

-

K

K

R

A

E

G

G

I

V

R

I

Y

K

T

S

A

E

L

I

T

V

P

A

N

H

I

S

K
x
R

G
x
A

Y

V

E

K

R

R

A

D

K

I

Q

E

A

V

G

G

A

A

-

E

-

I

-

E

-

A

D

D

E

R

V

I

A

A

I

I

F
|
F

A

Y

S

G

A

I

S

S

E

D

G

T

F

H

S

L

Q

K

K

A

N

K

I
x
H

N

H

C

T

S

T

I

R

E

D

E

E

S

A

F

L

E

R

R

S

F

I

A

A

P

E

I

T

L

V

E

S

T

Y

A

A

K

K

A

S

D

H

S

G

I

V

P

K

V

V

R
|
R

G

F

Y
x
T

V

A

S
x
E

C

D

V

A

V

T

E

R

C

A

P

D

Y

Y

D

-

G

-

P

-

T

-

P

-

V

-

Q

Q

N

Y

T

L

A

L

K

E

V

V

S

I

E

K

R

T

L

V

L

R

Q

D

M

A

G

G

C

A

Y

D

E

R

V

V

S
|
S

L

I

G

A

D

D

T
|
T

I

V

G

G

A

V

A

L

I

Y

P

P

E

S

T

R

T

T

E

R

A

E

M

L

L

F

D

K

A

D

L

L

L

T

K

S

V

R

V

F

P

P

A

D

E

I

K

E

L

F

A

D

G

I

H
|
H

F

A

H
|
H

D

N

T

D

H

L

D

G

F

M

A

A

L

V

A

A

N

N

I

V

M

L

S

A

I

A

K

E

M

G

G

G

L

A

R

T

T

I

F

I

D

H

T

T

A

T

I

L

G

N

G

G

L

L

G

G

binding 2-oxoglutaric acid: R30 (= R13), R154 (= R137), T156 (≠ Y139), E158 (≠ S141), S184 (= S173), T188 (= T177), H216 (= H205), H218 (= H207)
binding coenzyme a: V67 (= V49), R96 (≠ K83), A97 (≠ G84), F116 (= F99), H128 (≠ I111), E158 (≠ S141)
binding zinc ion: E31 (≠ D14), H216 (= H205), H218 (= H207)

2nx9B Crystal structure of the carboxyltransferase domain of the oxaloacetate decarboxylase na+ pump from vibrio cholerae (see paper)
30% identity, 46% coverage: 152:283/287 of query aligns to 151:278/453 of 2nx9B

query
sites
2nx9B

T

S

P

P

V

V

Q

H

N

N

T

L

-

Q

-

T

-

W

A

V

K

D

V

V

S

A

E

Q

R

Q

L

L

L

A

Q

E

M

L

G

G

C

V

Y

D

E

S

V

I

S

A

L

L

G
x
K

D

D

T

M

I

A

G

G

A

I

A

L

I

T

P

P

E

Y

T

A

E

E

A

E

M

L

L

V

D

S

A

T

L

L

L

K

K

K

V

Q

V

V

P

D

A

V

E

E

K

-

L

L

A

H

G

L

H
|
H

F

C

H
|
H

D

S

T

T

H

A

D

G

F

L

A

A

L

D

A

M

N

T

I

L

M

L

S

K

S

A

I

I

K

E

M

A

G

G

L

V

R

D

T

R

F

V

D

D

T

T

A

A

I

I

G

S

L

M

G

S

G

G

C

T

P

Y

Y

G

A

H

P

P

G

A

A

T

K

E

G

S

N

L

V

V

S

A

T

T

L

L

S

Q

V

G

A

T

K

G

M

-

A

-

K

-

L

-

D

-

Y

Y

D

D

T

T

N

G

L

L

D

D

I

I

E

A

K

K

L

L

E

E

Q

Q

T

I

Q

A

D

A

F

Y

I

F

L

R

S

D

I

V

K

R

E

K

active site: K177 (≠ G175), H206 (= H205), H208 (= H207)
binding zinc ion: H206 (= H205), H208 (= H207)

Sites not aligning to the query:

active site: 16, 19, 120, 341
binding zinc ion: 16

Q8F3Q1 (R)-citramalate synthase CimA; LiCMS; EC 2.3.3.21 from Leptospira interrogans serogroup Icterohaemorrhagiae serovar Lai (strain 56601) (see 2 papers)
22% identity, 81% coverage: 4:236/287 of query aligns to 7:238/516 of Q8F3Q1

query
sites
Q8F3Q1

R

R

L

L

T

E

I

I

F

L

E

D

M

V

G

T

P

L

R
|
R

D
|
D

G

G

L

E

Q

Q

N

T

E

R

K

G

T

V

L

S

I

F

P

S

T

T

A

S

Q

E

K

K

I

L

E

N

-

I

-

A

-

K

-

F

L

L

I

L

N

Q

R

K

L

L

S

N

-

V

-

D

-

R

-

V

E

E

C

I

G

A

F

S

K

A

K

R

I

V

E

S

T

K

S

G

S

E

F

L

V

E

S

T

P

V

K

Q

W

K

V

I

P

M

Q

E

M

W

A

A

D

A

A

T

S

E

Q

Q

V

L

F

T

E

E

G

R

I

I

T

-

R

-

K

-

A

-

G

-

I

-

R

E

Y

I

T
x
L

A

G

L
x
F

T

V

P

D

N

G

I

N

K

K

G

T

Y

V

E

D

R

W

A

I

K

K

Q

D

A

S

G

G

A

A

D

K

E

V

V

L

A

N

I

L

F
x
L

A

T

S

K

A

G

S

S

E

L

G

H

F

H

S

L

Q

E

K

K

N

Q

I

L

N

G

C

K

S

T

I

P

E

K

E

E

S

F

F

F

E

T

R

D

F

V

A

S

P

F

I

V

L

I

E

E

T

Y

A

A

K

I

A

K

D

S

S

G

I

L

P

K

V

I

R

N

G

V

Y
|
Y

V

L

S
x
E

C

D

V

W

V

S

E

N

C

G

P

F

Y

R

D

N

G

S

P

P

T

D

P

Y

V

V

Q

K

N

S

T

-

A

-

K

-

V

L

S

V

E

E

R

H

L

L

L

S

Q

K

M

E

G

H

C

I

Y

E

E

R

V

I

S

F

L

L

G

P

D

D

T
|
T

I

L

G

G

A

V

A

L

I

S

P

P

E

E

T

E

T

T

E

F

A

Q

M

G

L

V

D

D

A

S

L

L

L

I

K

Q

V

K

V

Y

P

P

A

D

E

I

K

H

L

F

A

E

G

F

H

H

F

G

H

H

D

N

T

D

H

Y

D

D

F

L

A

S

L

V

A

A

N

N

I

S

M

L

S

Q

S

A

I

I

K

R

M

A

G

G

L

V

R

K

T

G

F

L

D

H

T

A

A

S

I

I

G

N

G

G

L

L

G

G

R16 (= R13) mutation R->K,Q: Loss of activity.
RD 16:17 (= RD 13:14) binding pyruvate
D17 (= D14) 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 (≠ T76) 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 (≠ L78) mutation to A: 5-fold increase in Km for acetyl-CoA and 120-fold decrease in kcat.
L104 (≠ F99) mutation to V: 1.8-fold increase in Km for pyruvate and 3.4-fold decrease in kcat.
Y144 (= Y139) 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 (≠ S141) mutation E->D,Q: Minor effects on the binding of acetyl-CoA, but causes a strong decrease in kcat.
T179 (= T177) binding pyruvate; 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.

3bliA Crystal structure of the catalytic domain of licms in complexed with pyruvate and acetyl-coa (see paper)
22% identity, 81% coverage: 4:236/287 of query aligns to 1:232/311 of 3bliA

query
sites
3bliA

R

R

L

L

T

E

I

I

F

L

E

D

M

V

G

T

P

L

R
|
R

D
|
D

G

G

L

E

Q
|
Q

N

T

E

R

K

G

T

V

L

S

I

F

P

S

T

T

A

S

Q

E

K

K

I

L

E

N

-

I

-

A

-

K

-

F

L

L

I

L

N

Q

R

K

L

L

S

N

-

V

-

D

-

R

-

V

E

E

C

I

G

A

F

S

K

A

K
x
R

I
x
V

E

S

T

K

S

G

S

E

F

L

V

E

S

T

P

V

K

Q

W

K

V

I

P

M

Q

E

M

W

A

A

D

A

A

T

S

E

Q

Q

V

L

F

T

E

E

G

R

I

I

T

-

R

-

K

-

A

-

G

-

I

-

R

E

Y

I

T

L

A

G

L

F

T

V

P

D

N

G

I

N

K

K

G

T

Y

V

E

D

R

W

A

I

K

K

Q

D

A

S

G

G

A

A

D

K

E

V

V

L

A

N

I

L

F

L

A

T

S

K

A

G

S

S

E

L

G

H

F

H

S

L

Q

E

K

K

N

Q

I

L

N

G

C

K

S

T

I

P

E

K

E

E

S

F

F

F

E

T

R

D

F

V

A

S

P

F

I

V

L

I

E

E

T

Y

A

A

K

I

A

K

D

S

S

G

I

L

P

K

V

I

R

N

G

V

Y
|
Y

V

L

S
x
E

C

D

V

W

V

S

E

N

C

G

P

F

Y

R

D

N

G

S

P

P

T

D

P

Y

V

V

Q

K

N

S

T

-

A

-

K

-

V

L

S

V

E

E

R

H

L

L

L

S

Q

K

M

E

G

H

C

I

Y

E

E

R

V

I

S

F

L

L

G
x
P

D

D

T
|
T

I

L

G

G

A

V

A

L

I

S

P

P

E

E

T

E

T

T

E

F

A

Q

M

G

L

V

D

D

A

S

L

L

L

I

K

Q

V

K

V

Y

P

P

A

D

E

I

K

H

L

F

A

E

G

F

H
|
H

F

G

H
|
H

D

N

T

D

H

Y

D

D

F

L

A

S

L

V

A

A

N

N

I

S

M

L

S

Q

S

A

I

I

K

R

M

A

G

G

L

V

R

K

T

G

F

L

D

H

T

A

A

S

I

I

G

N

G

G

L

L

G

G

active site: Q14 (= Q17)
binding acetyl coenzyme *a: Q14 (= Q17), R47 (≠ K42), V48 (≠ I43), E140 (≠ S141)
binding pyruvic acid: R10 (= R13), Y138 (= Y139), P171 (≠ G175), T173 (= T177)
binding zinc ion: D11 (= D14), H201 (= H205), H203 (= H207)

2zyfA Crystal structure of homocitrate synthase from thermus thermophilus complexed with magnesuim ion and alpha-ketoglutarate (see paper)
27% identity, 78% coverage: 13:236/287 of query aligns to 12:220/314 of 2zyfA

query
sites
2zyfA

R
|
R

D
x
E

G

G

L

E

Q
|
Q

N

F

E

E

K

K

T

A

L

N

I

F

P

S

T

T

A

Q

Q

D

K

K

I

V

E

E

L

I

I

A

N

K

R

A

L

L

S

D

E

E

C

F

G

G

F

I

K

E

K

Y

I

I

E

E

T

V

S

T

S

-

F

-

V

-

S

T

P

P

K

V

W

A

V

S

P

P

Q

Q

M

S

A

R

D

K

A

D

S

A

Q

E

V

V

F

L

E

A

G

S

I

L

T

G

R

L

K

K

A

A

G

K

I

V

R

-

Y

V

T

T

A
x
H

L

I

T

Q

P

C

N

R

I

L

K

D

G

A

Y

A

E

K

R

V

A

A

K

V

Q

E

A

T

G

G

A

V

D

Q

E

G

V

I

A

D

I

L

F
x
L

A

F

S

G

A

T

S

S

E

K

G

G

F

-

S

-

Q

-

K

R

N

D

I

I

N

P

C

R

S

I

I

I

E

E

S

A

F

K

E

E

R

V

F

I

A

A

P

Y

I

I

L

R

E

E

T

A

A

A

K

P

A

H

D

-

S

-

I

-

P

-

V

-

R

-

G

-

Y

-

V

-

S

-

C

-

V

-

V

V

E

E

C

V

P
x
R

Y

F

D

S

G

A

P

-

T

-

P

-

V

-

Q

E

N

D

T

T

A

F

K

R

V

S

S

E

E

E

R

Q

L

D

L

L

Q

-

M

L

G

A

C

V

Y

Y

E

E

-

A

-

V

-

A

-

P

-

Y

-

V

-

D

-

R

V

V

S

G

L

L

G

A

D

D

T
|
T

I

V

G

G

A

V

A

A

I

T

P

P

E

R

T

Q

T

V

E

Y

A

A

M

L

L

V

D

R

A

E

L

V

L

R

K

R

V

V

-

G

P

P

A

R

E

V

K

D

L

I

A

E

G

F

H
|
H

F

G

H
|
H

D

N

T

D

H

T

D

G

F

C

A

A

L

I

A

A

N

N

I

A

M

Y

S

E

S

A

I

I

K

E

M

A

G

G

L

A

R

T

T

H

F

V

D

D

T

T

A

T

I

I

G

L

G

G

L

I

G

G

active site: Q16 (= Q17)
binding 2-oxoglutaric acid: R12 (= R13), H72 (≠ A77), L94 (≠ F99), R127 (≠ P147), T160 (= T177), H189 (= H205)
binding magnesium ion: E13 (≠ D14), H189 (= H205), H191 (= H207)

3a9iA Crystal structure of homocitrate synthase from thermus thermophilus complexed with lys (see paper)
27% identity, 78% coverage: 13:236/287 of query aligns to 11:219/347 of 3a9iA

query
sites
3a9iA

R
|
R

D
x
E

G

G

L

E

Q

Q

N

F

E

E

K

K

T

A

L

N

I

F

P

S

T

T

A

Q

Q

D

K

K

I

V

E

E

L

I

I

A

N

K

R

A

L

L

S

D

E

E

C

F

G

G

F

I

K

E

K

Y

I

I

E

E

T

V

S

T

S

-

F

-

V

-

S

T

P

P

K

V

W

A

V

S

P

P

Q

Q

M

S

A

R

D

K

A

D

S

A

Q

E

V

V

F

L

E

A

G

S

I

L

T

G

R

L

K

K

A

A

G

K

I

V

R

-

Y

V

T

T

A

H

L

I

T

Q

P

C

N

R

I

L

K

D

G

A

Y

A

E

K

R

V

A

A

K

V

Q

E

A

T

G

G

A

V

D

Q

E

G

V

I

A
x
D

I

L

F

L

A

F

S

G

A

T

S

S

E

K

G

Y

F

L

S

D

Q

I

K

P

N

R

I

I

N

-

C

-

S

-

I

I

E

E

S

A

F

K

E

E

R

V

F

I

A

A

P

Y

I

I

L

R

E

E

T

A

A

A

K

P

A

H

D

-

S

-

I

-

P

-

V

-

R

-

G

-

Y

-

V

-

S

-

C

-

V

-

V

V

E

E

C

V

P

R

Y

F

D
x
S

G

A

P

-

T

-

P

-

V

-

Q

E

N

D

T

T

A

F

K

R

V

S

S

E

E

E

R

Q

L

D

L

L

Q

-

M

L

G

A

C

V

Y

Y

E

E

-

A

-

V

-

A

-

P

-

Y

-

V

-

D

-

R

V

V

S

G

L

L

G

A

D

D

T
|
T

I

V

G

G

A

V

A

A

I

T

P

P

E

R

T

Q

T

V

E

Y

A

A

M

L

L

V

D

R

A

E

L

V

L

R

K

R

V

V

-

G

P

P

A

R

E

V

K

D

L

I

A

E

G

F

H
|
H

F

G

H
|
H

D

N

T

D

H

T

D

G

F

C

A

A

L

I

A

A

N

N

I

A

M

Y

S

E

S

A

I

I

K

E

M

A

G

G

L

A

R

T

T

H

F

V

D

D

T

T

A

T

I

I

G

L

G

G

L

I

G

G

binding cobalt (ii) ion: E12 (≠ D14), H188 (= H205), H190 (= H207)
binding lysine: R11 (= R13), D91 (≠ A97), S128 (≠ D149), T159 (= T177), H188 (= H205), H190 (= H207)

O87198 Homocitrate synthase; HCS; EC 2.3.3.14 from Thermus thermophilus (strain ATCC BAA-163 / DSM 7039 / HB27) (see paper)
26% identity, 78% coverage: 13:236/287 of query aligns to 12:226/376 of O87198

query
sites
O87198

R
|
R

D
x
E

G

G

L

E

Q

Q

N

F

E

E

K

K

T

A

L

N

I

F

P

S

T

T

A

Q

Q

D

K

K

I

V

E

E

L

I

I

A

N

K

R

A

L

L

S

D

E

E

C

F

G

G

F

I

K

E

K

Y

I

I

E

E

T

V

S

T

S

-

F

-

V

-

S

T

P

P

K

V

W

A

V

S

P

P

Q

Q

M

S

A

R

D

K

A

D

S

A

Q

E

V

V

F

L

E

A

G

S

I

L

T

G

R

L

K

K

A

A

G

K

I

V

R

-

Y

V

T

T

A
x
H

L

I

T

Q

P

C

N

R

I

L

K

D

G

A

Y

A

E

K

R

V

A

A

K

V

Q

E

A

T

G

G

A

V

D

Q

E

G

V

I

A
x
D

I

L

F

L

A

F

S

G

A

T

S

S

E

K

G

Y

F

L

S

R

Q

A

-

A

-

H

-

G

K

R

N

D

I

I

N

P

C

R

S

I

I

I

E

E

S

A

F

K

E

E

R

V

F

I

A

A

P

Y

I

I

L

R

E

E

T

A

A

A

K

P

A

H

D

-

S

-

I

-

P

-

V

-

R

-

G

-

Y

-

V

-

S

-

C

-

V

-

V

V

E

E

C

V

P
x
R

Y

F

D
x
S

G

A

P

-

T

-

P

-

V

-

Q

E

N

D

T

T

A

F

K

R

V

S

S

E

E

E

R

Q

L

D

L

L

Q

-

M

L

G

A

C

V

Y

Y

E

E

-

A

-

V

-

A

-

P

-

Y

-

V

-

D

-

R

V

V

S

G

L

L

G

A

D

D

T
|
T

I

V

G

G

A

V

A

A

I

T

P

P

E

R

T

Q

T

V

E

Y

A

A

M

L

L

V

D

R

A

E

L

V

L

R

K

R

V

V

-

G

P

P

A

R

E

V

K

D

L

I

A

E

G

F

H
|
H

F

G

H
|
H

D

N

T

D

H

T

D

G

F

C

A

A

L

I

A

A

N

N

I

A

M

Y

S

E

S

A

I

I

K

E

M

A

G

G

L

A

R

T

T

H

F

V

D

D

T

T

A

T

I

I

G

L

G

G

L

I

G

G

R12 (= R13) binding 2-oxoglutarate
E13 (≠ D14) binding Mg(2+)
H72 (≠ A77) 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 (≠ A97) binding L-lysine
R133 (≠ P147) binding 2-oxoglutarate
S135 (≠ D149) binding L-lysine
T166 (= T177) binding 2-oxoglutarate; binding L-lysine
H195 (= H205) binding Mg(2+)
H197 (= H207) binding Mg(2+)

2ztjA Crystal structure of homocitrate synthase from thermus thermophilus complexed with alpha-ketoglutarate (see paper)
26% identity, 78% coverage: 13:236/287 of query aligns to 12:218/312 of 2ztjA

query
sites
2ztjA

R
|
R

D
x
E

G

G

L

E

Q
|
Q

N

F

E

E

K

K

T

A

L

N

I

F

P

S

T

T

A

Q

Q

D

K

K

I

V

E

E

L

I

I

A

N

K

R

A

L

L

S

D

E

E

C

F

G

G

F

I

K

E

K

Y

I

I

E

E

T

V

S

T

S

-

F

-

V

-

S

T

P

P

K

V

W

A

V

S

P

P

Q

Q

M

S

A

R

D

K

A

D

S

A

Q

E

V

V

F

L

E

A

G

S

I

L

T

G

R

L

K

K

A

A

G

K

I

V

R

-

Y

V

T

T

A
x
H

L

I

T

Q

P

C

N

R

I

L

K

D

G

A

Y

A

E

K

R

V

A

A

K

V

Q

E

A

T

G

G

A

V

D

Q

E

G

V

I

A

D

I

L

F
x
L

A

F

S

G

A

-

S

-

E

-

G

-

F

-

S

T

Q

G

K

R

N

D

I

I

N

P

C

R

S

I

I

I

E

E

S

A

F

K

E

E

R

V

F

I

A

A

P

Y

I

I

L

R

E

E

T

A

A

A

K

P

A

H

D

-

S

-

I

-

P

-

V

-

R

-

G

-

Y

-

V

-

S

-

C

-

V

-

V

V

E

E

C

V

P
x
R

Y

F

D

S

G

A

P

-

T

-

P

-

V

-

Q

E

N

D

T

T

A

F

K

R

V

S

S

E

E

E

R

Q

L

D

L

L

Q

-

M

L

G

A

C

V

Y

Y

E

E

-

A

-

V

-

A

-

P

-

Y

-

V

-

D

-

R

V

V

S

G

L

L

G
x
A

D

D

T
|
T

I

V

G

G

A

V

A

A

I

T

P

P

E

R

T

Q

T

V

E

Y

A

A

M

L

L

V

D

R

A

E

L

V

L

R

K

R

V

V

-

G

P

P

A

R

E

V

K

D

L

I

A

E

G

F

H
|
H

F

G

H
|
H

D

N

T

D

H

T

D

G

F

C

A

A

L

I

A

A

N

N

I

A

M

Y

S

E

S

A

I

I

K

E

M

A

G

G

L

A

R

T

T

H

F

V

D

D

T

T

A

T

I

I

G

L

G

G

L

I

G

G

active site: Q16 (= Q17)
binding 2-oxoglutaric acid: R12 (= R13), H72 (≠ A77), L94 (≠ F99), R125 (≠ P147), A156 (≠ G175), T158 (= T177), H187 (= H205), H189 (= H207)
binding copper (ii) ion: E13 (≠ D14), H187 (= H205), H189 (= H207)

Q70AC7 Methylmalonyl-CoA carboxyltransferase 5S subunit; Transcarboxylase 5S subunit; EC 2.1.3.1 from Propionibacterium freudenreichii subsp. shermanii (see paper)
27% identity, 45% coverage: 154:282/287 of query aligns to 163:286/505 of Q70AC7

query
sites
Q70AC7

V

V

Q

E

N

G

T

Y

A

V

K

K

V

L

S

A

E

G

R

Q

L

L

Q

D

M

M

G

G

C

A

Y

D

E

S

V

I

S

A

L

L

G
x
K

D

D

T
x
M

I

A

G

A

A

L

I

K

P

P

E

Q

T

P

T

A

E

Y

A

D

M

I

L

I

D

K

A

A

L

I

L

K

K

D

V

T

V

Y

P

G

A

Q

E

K

-

T

K

Q

L

I

A

N

G

L

H

H

F

C

H

H

D

S

T

T

H

T

D

G

F

V

A

T

L

E

A

V

N

S

I

L

M

M

S

K

S

A

I

I

K

E

M

A

G

G

L

V

R

D

T

V

F

V

D

D

T

T

A

A

I

I

G

S

L

M

G

S

G

L

C

G

P

P

Y

-

A

-

P

-

G

-

A

-

K

-

G

G

N

H

V

N

S

P

T

T

L

E

S

S

V

V

A

A

K

E

M

M

A

L

K

E

L

G

L

T

D

G

Y

Y

D

T

T

T

N

N

L

L

D

D

I

Y

E

D

K

R

L

L

E

H

Q

K

T

I

Q

R

D

D

F

H

I

F

L

K

S

A

I

I

K

R

K184 (≠ G175) modified: N6-carboxylysine; partial; mutation K->A,E: Loss of activity.
M186 (≠ T177) mutation to I: Decreases activity by 98%.

Sites not aligning to the query:

59 A→T: Decreases activity by 96%.

1rr2A Propionibacterium shermanii transcarboxylase 5s subunit bound to 2- ketobutyric acid (see paper)
27% identity, 45% coverage: 154:282/287 of query aligns to 161:284/472 of 1rr2A

query
sites
1rr2A

V

V

Q

E

N

G

T

Y

A

V

K

K

V

L

S

A

E

G

R

Q

L

L

Q

D

M

M

G

G

C

A

Y

D

E

S

V

I

S

A

L

L

G
x
K

D

D

T

M

I

A

G

A

A

L

I

K

P

P

E

Q

T

P

T

A

E

Y

A

D

M

I

L

I

D

K

A

A

L

I

L

K

K

D

V

T

V

Y

P

G

A

Q

E

K

-

T

K

Q

L

I

A

N

G

L

H
|
H

F

C

H
|
H

D

S

T

T

H

T

D

G

F

V

A

T

L

E

A

V

N

S

I

L

M

M

S

K

S

A

I

I

K

E

M

A

G

G

L

V

R

D

T

V

F

V

D

D

T

T

A

A

I

I

G

S

L

M

G

S

G

L

C

G

P

P

Y

-

A

-

P

-

G

-

A

-

K

-

G

G

N

H

V

N

S

P

T

T

L

E

S

S

V

V

A

A

K

E

M

M

A

L

K

E

L

G

L

T

D

G

Y

Y

D

T

T

T

N

N

L

L

D

D

I

Y

E

D

K

R

L

L

E

H

Q

K

T

I

Q

R

D

D

F

H

I

F

L

K

S

A

I

I

K

R

active site: K182 (≠ G175), H213 (= H205), H215 (= H207)
binding 2-ketobutyric acid: K182 (≠ G175)
binding cobalt (ii) ion: K182 (≠ G175), H213 (= H205), H215 (= H207)

Sites not aligning to the query:

1rqeA Propionibacterium shermanii transcarboxylase 5s subunit bound to oxaloacetate (see paper)
27% identity, 45% coverage: 154:282/287 of query aligns to 161:284/472 of 1rqeA

query
sites
1rqeA

V

V

Q

E

N

G

T

Y

A

V

K

K

V

L

S

A

E

G

R

Q

L

L

Q

D

M

M

G

G

C

A

Y

D

E

S

V

I

S

A

L

L

G
x
K

D

D

T

M

I

A

G

A

A

L

I

K

P

P

E

Q

T

P

T

A

E

Y

A

D

M

I

L

I

D

K

A

A

L

I

L

K

K

D

V

T

V

Y

P

G

A

Q

E

K

-

T

K

Q

L

I

A

N

G

L

H
|
H

F

C

H
|
H

D

S

T

T

H

T

D

G

F

V

A

T

L

E

A

V

N

S

I

L

M

M

S

K

S

A

I

I

K

E

M

A

G

G

L

V

R

D

T

V

F

V

D

D

T

T

A

A

I

I

G

S

L

M

G

S

G

L

C

G

P

P

Y

-

A

-

P

-

G

-

A

-

K

-

G

G

N

H

V

N

S

P

T

T

L

E

S

S

V

V

A

A

K

E

M

M

A

L

K

E

L

G

L

T

D

G

Y

Y

D

T

T

T

N

N

L

L

D

D

I

Y

E

D

K

R

L

L

E

H

Q

K

T

I

Q

R

D

D

F

H

I

F

L

K

S

A

I

I

K

R

active site: K182 (≠ G175), H213 (= H205), H215 (= H207)
binding cobalt (ii) ion: H213 (= H205), H215 (= H207)
binding oxaloacetate ion: K182 (≠ G175)

Sites not aligning to the query:

1rqbA Propionibacterium shermanii transcarboxylase 5s subunit (see paper)
27% identity, 45% coverage: 154:282/287 of query aligns to 161:284/472 of 1rqbA

query
sites
1rqbA

V

V

Q

E

N

G

T

Y

A

V

K

K

V

L

S

A

E

G

R

Q

L

L

Q

D

M

M

G

G

C

A

Y

D

E

S

V

I

S

A

L

L

G
x
K

D

D

T

M

I

A

G

A

A

L

I

K

P

P

E

Q

T

P

T

A

E

Y

A

D

M

I

L

I

D

K

A

A

L

I

L

K

K

D

V

T

V

Y

P

G

A

Q

E

K

-

T

K

Q

L

I

A

N

G

L

H
|
H

F

C

H
|
H

D

S

T

T

H

T

D

G

F

V

A

T

L

E

A

V

N

S

I

L

M

M

S

K

S

A

I

I

K

E

M

A

G

G

L

V

R

D

T

V

F

V

D

D

T

T

A

A

I

I

G

S

L

M

G

S

G

L

C

G

P

P

Y

-

A

-

P

-

G

-

A

-

K

-

G

G

N

H

V

N

S

P

T

T

L

E

S

S

V

V

A

A

K

E

M

M

A

L

K

E

L

G

L

T

D

G

Y

Y

D

T

T

T

N

N

L

L

D

D

I

Y

E

D

K

R

L

L

E

H

Q

K

T

I

Q

R

D

D

F

H

I

F

L

K

S

A

I

I

K

R

active site: K182 (≠ G175), H213 (= H205), H215 (= H207)
binding cobalt (ii) ion: K182 (≠ G175), H213 (= H205), H215 (= H207)

Sites not aligning to the query:

active site: 21, 125, 347
binding cobalt (ii) ion: 21

Query Sequence

>WP_068010797.1 NCBI__GCF_001623255.1:WP_068010797.1
MSKRLTIFEMGPRDGLQNEKTLIPTAQKIELINRLSECGFKKIETSSFVSPKWVPQMADA
SQVFEGITRKAGIRYTALTPNIKGYERAKQAGADEVAIFASASEGFSQKNINCSIEESFE
RFAPILETAKADSIPVRGYVSCVVECPYDGPTPVQNTAKVSERLLQMGCYEVSLGDTIGA
AIPETTEAMLDALLKVVPAEKLAGHFHDTHDFALANIMSSIKMGLRTFDTAIGGLGGCPY
APGAKGNVSTLSVAKMAKLLDYDTNLDIEKLEQTQDFILSIKEAASL

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