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)
29% identity, 93% coverage: 4:269/287 of query aligns to 78:341/370 of Q8TB92

query
sites
Q8TB92

V

V

K

K

I

I

I

V

E

E

C

V

-

G

P

P

R
|
R

D

D

A

G

M

L

Q

Q

G

N

I

E

K

K

M

V

F

I

I

V

P

P

T

T

E

D

Q

I

K

K

V

I

Q

E

Y

F

I

I

Q

N

S

R

L

L

L

S

R

Q

C

T

G

G

F

L

D

S

T

V

L

I

D

E

F

V

G

T

S

S

F

F

V

V

S

S

P

S

K

R

A

W

I

V

P

P

Q

Q

M

M

Q

A

D

D

T

H

A

T

E

E

V

V

L

M

A

K

Q

G

L

I

D

H

L

-

S

Q

E

Y

T

P

K

G

T

V

K

R

L

Y

L

P

A

V

I

L

I

T

A

P

N

N

T

L

K

Q

G

G

-

F

-

H

A

H

E

A

M

V

A

A

S

A

V

G

H

A

N

T

E

E

I

I

Q

S

Y

V

L

F

G

G

F

-

P

-

F

-

S

A

I

A

S

S

E

E

N

S

F

F

Q

S

M

K

R

K

N

N

T

I

H

N

K

C

T

S

I

I

A

E

E

E

S

S

I

M

V

G

T

K

L

F

Q

E

E

E

I

V

L

V

E

K

I

S

A

A

N

R

K

H

T

M

N

N

K

I

E

P

V

A

V

R

A

G

Y

Y

L

V

S

S

M

C

G

A

F

L

G

G

N

C

P

P

Y

Y

G

E

D

G

P

S

W

I

N

T

V

P

D

Q

I

K

V

V

G

T

E

E

W

V

T

S

E

K

K

R

L
|
L

A

Y

N

G

M

M

G

G

V

C

T

Y

I

E

L

I

S

S

L

L

S

G

D

D

T

T

V

I

G

G

S

V

S

G

T

T

A

P

E

G

D

S

I

M

D

K

Y

R

L

M

F

L

S

E

N

S

L

V

I

M

P

K

K

E

Y

I

P

P

N

P

I

G

E

A

F

L

G

A

A

V

H
|
H

L

C

H

H

T

D

T

T

P

Y

D

G

A

Q

W

A

F

L

E

A

K

N

V

I

D

L

A

T

A

A

Y

L

K

Q

A

M

G

G

C

I

I

N

R

V

F

V

D

D

G

S

A

A

I

V

K

S

G

G

F

L

G

G

C

C

P

P

M

Y

A

A

K

K

D

G

D

A

L

-

T

S

G

G

N

N

M

V

P

A

T

T

E

E

K

D

M

L

L

I

S

Y

Y

M

F

L

T

N

A

G

N

L

K

G

A

L

A

N

T

T

N

G

V

V

Q

N

M

L

R86 (= R11) 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.

P13703 Hydroxymethylglutaryl-CoA lyase; HL; HMG-CoA lyase; 3-hydroxy-3-methylglutarate-CoA lyase; EC 4.1.3.4 from Pseudomonas mevalonii (see paper)
29% identity, 94% coverage: 1:269/287 of query aligns to 1:267/301 of P13703

query
sites
P13703

M

M

K

Q

P

A

V

V

K

K

I

V

I

F

E

E

C

V

-

G

P

P

R

R

D

D

A

G

M

L

Q

Q

G

N

I

E

K

R

M

Q

F

P

I

L

P

S

T

V

E

A

Q

A

K

R

V

V

Q

G

Y

L

I

I

Q

G

S

E

L

L

L

A

R

G

C

T

G

G

F

L

D

R

T

H

L

I

D

E

F

A

G

G

S

A

F

F

V

V

S

S

P

P

K

R

A

W

I

V

P

P

Q

Q

M

M

Q

A

D

G

T

S

A

D

E

E

V

V

L

L

A

R

Q

Q

L

L

D

P

L

-

S

S

E

N

T

D

K

G

T

V

K

S

L

Y

L

T

A

A

I

L

I

V

A

P

N

N

T

R

K

Q

G

G

A

F

E

E

M

A

A

A

S

Q

V

R

H

A

N

G

E

C

I

R

Q

E

Y

V

L

A

G

V

F

F

P

A

F

-

S

A

I

A

S

S

E

E

N

A

F

F

Q

S

M

R

R

N

N

N

T

I

H

N

K

C

T

S

I

I

A

D

E

E

S

S

I

F

V

E

T

R

L

F

Q

T

E

P

I

V

L

L

E

R

I

A

A

A

N

N

K

E

T

A

N

S

K

I

E

R

V

V

V

R

A

G

Y

Y

L

V

S

S

M

C

G

V

F

L

G

G

N

C

P

P

Y

F

G

S

D

G

P

A

W

V

N

A

V

P

D

E

I

A

V

V

G

A

E

K

W

V

T

A

E

R

K

R

L

L

A

Y

N

E

M

L

G

G

V

C

T

Y

I

E

L

I

S

S

L

L

S

G

D

D

T

T

V

I

G

G

S

A

S

G

T

R

A

P

E

D

D

E

I

T

D

A

Y

Q

L

L

F

F

S

E

N

L

L

C

I

A

P

R

K

Q

Y

L

P

P

N

V

I

A

E

A

F

L

G

A

A

G

H

H

L

F

H

H

T

D

T

T

P

W

D

G

A

M

W

A

F

I

E

A

K

N

V

V

D

H

A

A

Y

L

K

A

A

Q

G

G

C

V

I

R

R

T

F

F

D

D

G

S

A

S

I

V

K

A

G

G

F

L

G

G

C
|
C

P

P

M

Y

A

S

K

P

D

-

D

G

L

A

T

S

G

G

N

N

M

V

P

A

T

T

E

E

K

D

M

L

L

L

S

Y

Y

L

F

L

T

H

A

G

N

L

K

G

A

Y

A

S

T

T

N

G

V

V

Q

D

M

L

C237 (= C238) active site

3mp3B Crystal structure of human lyase in complex with inhibitor hg-coa (see paper)
30% identity, 99% coverage: 2:284/287 of query aligns to 4:284/296 of 3mp3B

query
sites
3mp3B

K

K

P

R

V

V

K

K

I

I

I

V

E

E

C

V

-

G

P

P

R
|
R

D
|
D

A

G

M

L

Q
|
Q

G

N

I

E

K

K

M

N

F

I

I

V

P

S

T

T

E

P

Q

V

K

K

V

I

Q

K

Y

L

I

I

Q

D

S

M

L

L

L

S

R

E

C

A

G

G

F

L

D

S

T

V

L

I

D

E

F

T

G

T

S

S

F
|
F

V
|
V

S
|
S

P

P

K

K

A
x
W

I

V

P

P

Q

Q

M

M

Q

G

D

D

T

H

A

T

E

E

V

V

L

L

A

K

Q

G

L

I

D

Q

L

-

S

K

E

F

T

P

K

G

T

I

K

N

L

Y

L

P

A

V

I

L

I

T

A
x
P

N
|
N

T

L

K
|
K

G
|
G

-

F

-

E

A

A

E

A

M

V

A

A

S

A

V

G

H

A

N

K

E

E

I

V

Q

V

Y

I

L

F

G

G

F

-

P

-

F

-

S

A

I

A

S

S

E

E

N

L

F

F

Q

T

M

K

R

K

N
|
N

T

I

H

N

K

C

T

S

I

I

A

E

E

E

S

S

I

F

V

Q

T
x
R

L

F

Q

D

E

A

I

I

L

L

E

K

I

A

A

A

N

Q

K

S

T

A

N

N

K

I

E

S

V

V

V

R

A

G

Y
|
Y

L

V

S
|
S

M

C

G

A

F

L

G

G

N

C

P

P

Y

Y

G

E

D

G

P

K

W

I

N

S

V

P

D

A

I

K

V

V

G

A

E

E

W

V

T

T

E

K

K

K

L

F

A

Y

N

S

M

M

G

G

V

C

T

Y

I

E

L

I

S

S

L

L

S

G

D

D

T
|
T

V

I

G

G

S

V

S

G

T

T

A

P

E

G

D

I

I

M

D

K

Y

D

L

M

F

L

S

S

N

A

L

V

I

M

P

Q

K

E

Y

V

P

P

N

L

I

A

E

A

F

L

G

A

A

V

H
|
H

L

C

H
|
H

T

D

T

T

P

Y

D

G

A

Q

W

A

F

L

E

A

K

N

V

T

D

L

A

M

A

A

Y

L

K

Q

A

M

G

G

C

V

I

S

R

V

F

V

D

D

G

S

A

S

I

V

K

A

G

G

F

L

G

G

C

C

P

P

M

Y

A

A

K

Q

D

G

D

A

L

-

T

S

G

G

N

N

M

L

P

A

T

T

E

E

K

D

M

L

L

V

S

Y

Y

M

F

L

T

E

A

G

N

L

K

G

A

I

A

H

T

T

N

G

V

V

Q

N

M

L

T

Q

S

K

F

L

E

L

A

E

A

A

Y

G

N

N

E

F

A

I

L

C

K

Q

I

A

F

L

N

N

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 (≠ A79), N82 (= N80), K84 (= K82), G85 (= G83), N111 (= N110), R122 (≠ T121), Y140 (= Y139), S142 (= S141), T178 (= T177), H206 (= H205)
binding magnesium ion: D15 (= D12), H206 (= H205), H208 (= H207)

2cw6A Crystal structure of human hmg-coa lyase: insights into catalysis and the molecular basis for hydroxymethylglutaric aciduria (see paper)
30% identity, 99% coverage: 2:284/287 of query aligns to 4:284/296 of 2cw6A

query
sites
2cw6A

K

K

P

R

V

V

K

K

I

I

I

V

E

E

C

V

-

G

P

P

R

R

D
|
D

A

G

M

L

Q
|
Q

G

N

I

E

K

K

M

N

F

I

I

V

P

S

T

T

E

P

Q

V

K

K

V

I

Q

K

Y

L

I

I

Q

D

S

M

L

L

L

S

R

E

C

A

G

G

F

L

D

S

T

V

L

I

D

E

F

T

G

T

S

S

F

F

V

V

S

S

P

P

K

K

A

W

I

V

P

P

Q

Q

M

M

Q

G

D

D

T

H

A

T

E

E

V

V

L

L

A

K

Q

G

L

I

D

Q

L

-

S

K

E

F

T

P

K

G

T

I

K

N

L

Y

L

P

A

V

I

L

I

T

A

P

N

N

T

L

K

K

G

G

-

F

-

E

A

A

E

A

M

V

A

A

S

A

V

G

H

A

N

K

E

E

I

V

Q

V

Y

I

L
x
F

G

G

F

-

P

-

F

-

S

A

I

A

S

S

E

E

N

L

F

F

Q

T

M

K

R

K

N

N

T

I

H

N

K

C

T

S

I

I

A

E

E

E

S

S

I

F

V

Q

T

R

L

F

Q

D

E

A

I

I

L

L

E

K

I

A

A

A

N

Q

K

S

T

A

N

N

K

I

E

S

V

V

V

R

A

G

Y

Y

L

V

S

S

M

C

G

A

F

L

G

G

N

C

P

P

Y

Y

G

E

D

G

P

K

W

I

N

S

V

P

D

A

I

K

V

V

G

A

E

E

W

V

T

T

E

K

K

K

L

F

A

Y

N

S

M

M

G

G

V

C

T

Y

I

E

L

I

S

S

L

L

S

G

D

D

T

T

V

I

G

G

S

V

S

G

T

T

A

P

E

G

D

I

I

M

D

K

Y

D

L

M

F

L

S

S

N

A

L

V

I

M

P

Q

K

E

Y

V

P

P

N

L

I

A

E

A

F

L

G

A

A

V

H
|
H

L

C

H
|
H

T

D

T

T

P

Y

D

G

A

Q

W

A

F

L

E

A

K

N

V

T

D

L

A

M

A

A

Y

L

K

Q

A

M

G

G

C

V

I

S

R

V

F

V

D

D

G

S

A

S

I

V

K

A

G

G

F

L

G

G

C

C

P

P

M

Y

A

A

K

Q

D

G

D

A

L

-

T

S

G

G

N
|
N

M

L

P

A

T

T

E

E

K

D

M

L

L

V

S

Y

Y

M

F

L

T

E

A

G

N

L

K

G

A

I

A

H

T

T

N

G

V

V

Q

N

M

L

T

Q

S

K

F

L

E

L

A

E

A

A

Y

G

N

N

E

F

A

I

L

C

K

Q

I

A

F

L

N

N

binding 3-hydroxypentanedioic acid: Q18 (= Q15), F100 (≠ L96)
binding magnesium ion: D15 (= D12), H206 (= H205), H208 (= H207), N248 (= N248)

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)
30% identity, 99% coverage: 2:284/287 of query aligns to 31:311/325 of P35914

query
sites
P35914

K

K

P

R

V

V

K

K

I

I

I

V

E
|
E

C

V

-

G

P

P

R
|
R

D
|
D

A

G

M

L

Q

Q

G

N

I

E

K
|
K

M

N

F

I

I

V

P

S

T

T

E

P

Q

V

K

K

V

I

Q

K

Y

L

I

I

Q

D

S

M

L

L

L

S

R

E

C

A

G

G

F

L

D

S

T

V

L

I

D
x
E

F

T

G

T

S

S

F

F

V

V

S

S

P

P

K

K

A

W

I

V

P

P

Q

Q

M

M

Q

G

D

D

T

H

A

T

E

E

V

V

L

L

A

K

Q

G

L

I

D

Q

L

-

S

K

E

F

T

P

K

G

T

I

K

N

L

Y

L

P

A

V

I

L

I

T

A

P

N

N

T

L

K

K

G

G

-

F

-

E

A

A

E

A

M

V

A

A

S

A

V

G

H

A

N

K

E

E

I

V

Q

V

Y

I

L

F

G

G

F

-

P

-

F

-

S

A

I

A

S

S

E

E

N

L

F

F

Q

T

M

K

R

K

N

N

T

I

H

N

K

C

T
x
S

I

I

A

E

E

E

S

S

I

F

V

Q

T

R

L

F

Q

D

E

A

I

I

L

L

E

K

I

A

A

A

N

Q

K

S

T

A

N

N

K

I

E

S

V

V

V

R

A

G

Y

Y

L

V

S

S

M

C

G

A

F

L

G

G

N
x
C

P

P

Y

Y

G

E

D

G

P

K

W

I

N

S

V

P

D

A

I

K

V

V

G

A

E

E

W

V

T

T

E

K

K

K

L
x
F

A

Y

N

S

M

M

G

G

V

C

T

Y

I

E

L
x
I

S

S

L

L

S
x
G

D
|
D

T

T

V

I

G

G

S

V

S

G

T

T

A

P

E

G

D

I

I

M

D

K

Y

D

L

M

F

L

S

S

N

A

L

V

I

M

P

Q

K

E

Y

V

P

P

N

L

I

A

E

A

F

L

G

A

A

V

H
|
H

L

C

H

H

T

D

T

T

P

Y

D

G

A

Q

W

A

F

L

E

A

K

N

V

T

D

L

A

M

A

A

Y

L

K

Q

A

M

G

G

C

V

I

S

R

V

F

V

D

D

G

S

A

S

I

V

K

A

G

G

F

L

G

G

C

C

P

P

M

Y

A

A

K

Q

D

G

D

A

L

-

T

S

G

G

N

N

M

L

P

A

T

T

E
|
E

K
x
D

M

L

L

V

S

Y

Y

M

F

L

T

E

A

G

N

L

K

G

A

I

A

H

T

T

N

G

V

V

Q

N

M

L

T

Q

S

K

F

L

E

L

A

E

A

A

Y

G

N

N

E

F

A

I

L

C

K

Q

I

A

F

L

N

N

E37 (= E8) 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 (= K18) to N: in HMGCLD; abolishes almost all enzymatic activity
E72 (≠ D42) mutation to A: Loss of activity, and reduced affinity for metal cofactor and substrate.
S142 (≠ T114) to F: in HMGCLD; activity lower than 5% respect to the wild-type
C174 (≠ N146) 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 (≠ L172) to F: in HMGCLD; activity lower than 5% respect to the wild-type
G203 (≠ S175) 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 (= E252) mutation to A: Reduced thermal stability, but normal activity.
D280 (≠ K253) mutation to A: Normal activity.

Sites not aligning to the query:

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

6ndsA Structure of an hmg-coa lyase from acenitobacter baumannii in complex with coenzyme a and 3-methylmalate
31% identity, 86% coverage: 10:256/287 of query aligns to 15:257/305 of 6ndsA

query
sites
6ndsA

P

P

R

R

D
|
D

A

G

M

L

Q

Q

G

I

I

E

K

P

M

T

F

W

I

V

P

P

T

T

E

D

Q

K

K

K

V

I

Q

D

Y

L

I

I

Q

N

S

Q

L

L

L

S

R

T

C

M

G

G

F

F

D

S

T

R

L

I

D

E

F

A

G

G

S

S

F

F

V
|
V

S
|
S

P

P

K

K

A

A

I
|
I

P

P

Q

N

M

L

Q

R

D

D

T

G

A

E

E

E

V

V

L

F

A

T

Q

G

L

I

D

-

L

-

S

-

E

-

T

T

K

R

T

H

K

K

-

D

-

I

L

Y

L

V

A

G

I

L

I

I

A

P

N
|
N

T

L

K

K

G
|
G

A

A

E

-

M

L

A
x
R

S

A

V

V

H

E

N

A

E

N

I

A

Q

N

Y

E

L

L

G

N

F

L

P

V

F

L

S

S

I

A

S

S

E

Q

N

T

F

H

Q

N

M

L

R

A

N
|
N

T
x
M

H
x
R

K

M

T

T

I

K

A

A

E

Q

S

S

I

F

V

A

T

G

L

F

Q

T

E

E

I

I

L

V

E

E

-

Q

I

L

A

Q

N

G

K

K

T

T

N

-

K

-

E

Q

V

F

V

N

A

G

Y

T

L

V

S

A

M

T

G

T

F

F

G

G

N

C

P

P

Y

F

G

E

D

G

P

K

W

I

N

S

V

E

D

R

I

E

V

V

G

F

E

S

W

L

T

V

E

E

K

H

L

Y

A

L

N

K

M

L

G

G

V

I

T

H

I

N

L

I

S

T

L

L

S

A

D

D

T

T

V

T

G

G

S

M

S

A

T

N

A

P

E

V

D

Q

I

V

D

K

Y

R

L

I

F

V

S

S

N

H

L

V

I

L

P

S

K

L

Y

I

P

S

N

P

I

E

E

Q

F

L

G

T

A

L

H
|
H

L

F

H
|
H

T

N

T

T

P

R

D

G

A

L

W

G

F

L

E

T

K

N

V

V

D

L

A

A

Y

Y

K

E

A

V

G

G

C

A

I

R

R

R

F

F

D

D

G

A

A

A

I

L

K

G

G

G

F

L

G

G

C

C

P

P

M

F

A

A

K

P

D

G

D

A

L

-

T

S

G

G

N

N

M

I

P

C

T

T

E

E

K

D

M

L

L

V

S

N

binding coenzyme a: V52 (= V47), S53 (= S48), I57 (= I52), N84 (= N80), G87 (= G83), R90 (≠ A87), N113 (= N110), M114 (≠ T111), R115 (≠ H112)
binding zinc ion: D17 (= D12), H207 (= H205), H209 (= H207)

3mp5B Crystal structure of human lyase r41m in complex with hmg-coa (see paper)
30% identity, 99% coverage: 2:284/287 of query aligns to 4:284/296 of 3mp5B

query
sites
3mp5B

K

K

P

R

V

V

K

K

I

I

I

V

E

E

C

V

-

G

P

P

R

M

D
|
D

A

G

M

L

Q
|
Q

G

N

I

E

K

K

M

N

F

I

I

V

P

S

T

T

E

P

Q

V

K

K

V

I

Q

K

Y

L

I

I

Q

D

S

M

L

L

L

S

R

E

C

A

G

G

F

L

D

S

T

V

L

I

D

E

F

T

G

T

S

S

F

F

V

V

S
|
S

P

P

K

K

A
x
W

I

V

P

P

Q

Q

M

M

Q

G

D

D

T

H

A

T

E

E

V

V

L

L

A

K

Q

G

L

I

D

Q

L

-

S

K

E

F

T

P

K

G

T

I

K

N

L

Y

L

P

A

V

I

L

I

T

A

P

N

N

T

L

K

K

G

G

-

F

-

E

A

A

E

A

M

V

A

A

S

A

V

G

H

A

N

K

E

E

I

V

Q

V

Y

I

L
x
F

G

G

F

-

P

-

F

-

S

A

I

A

S

S

E

E

N

L

F

F

Q

T

M

K

R

K

N
|
N

T

I

H
x
N

K

C

T

S

I

I

A

E

E

E

S

S

I

F

V

Q

T

R

L

F

Q

D

E

A

I

I

L

L

E

K

I

A

A

A

N

Q

K

S

T

A

N

N

K

I

E

S

V

V

V

R

A

G

Y
|
Y

L

V

S
|
S

M

C

G

A

F

L

G

G

N

C

P

P

Y

Y

G

E

D

G

P

K

W

I

N

S

V

P

D

A

I

K

V

V

G

A

E

E

W

V

T

T

E

K

K

K

L

F

A

Y

N

S

M

M

G

G

V

C

T

Y

I

E

L

I

S

S

L

L

S

G

D

D

T
|
T

V

I

G

G

S

V

S

G

T

T

A

P

E

G

D

I

I

M

D

K

Y

D

L

M

F

L

S

S

N

A

L

V

I

M

P

Q

K

E

Y

V

P

P

N

L

I

A

E

A

F

L

G

A

A

V

H
|
H

L

C

H
|
H

T

D

T

T

P

Y

D

G

A

Q

W

A

F

L

E

A

K

N

V

T

D

L

A

M

A

A

Y

L

K

Q

A

M

G

G

C

V

I

S

R

V

F

V

D

D

G

S

A

S

I

V

K

A

G

G

F

L

G

G

C
|
C

P

P

M

Y

A

A

K

Q

D

G

D

A

L

-

T

S

G

G

N

N

M

L

P

A

T

T

E

E

K

D

M

L

L

V

S

Y

Y

M

F

L

T

E

A

G

N

L

K

G

A

I

A

H

T

T

N

G

V

V

Q

N

M

L

T

Q

S

K

F

L

E

L

A

E

A

A

Y

G

N

N

E

F

A

I

L

C

K

Q

I

A

F

L

N

N

binding 3-hydroxy-3-methylglutaryl-coenzyme a: D15 (= D12), Q18 (= Q15), S51 (= S48), W54 (≠ A51), F100 (≠ L96), N111 (= N110), N113 (≠ H112), Y140 (= Y139), S142 (= S141), T178 (= T177), C239 (= C238)
binding magnesium ion: D15 (= D12), H206 (= H205), H208 (= H207)

Q8F3Q1 (R)-citramalate synthase CimA; LiCMS; EC 2.3.3.21 from Leptospira interrogans serogroup Icterohaemorrhagiae serovar Lai (strain 56601) (see 2 papers)
24% identity, 96% coverage: 11:286/287 of query aligns to 16:278/516 of Q8F3Q1

query
sites
Q8F3Q1

R
|
R

D
|
D

A

G

M

E

Q

Q

G

T

I

R

K

G

M

V

F

S

I

F

P

S

T

T

E

S

Q

E

K

K

V

L

Q

N

Y

I

I

A

Q

K

S

F

L

L

-

Q

R

K

C

L

G

N

F

V

D

D

T

R

L

V

D

E

F

I

G

A

S

S

-

A

F

R

V

V

S

S

P

K

K

G

A

E

I

L

P

E

Q

T

M

V

Q

Q

D

K

T

I

A

M

E

E

V

W

L

A

A

A

Q

T

L

E

D

Q

L

L

S

T

E

E

T

-

K

R

T

I

K

E

L

I

L
|
L

A

G

I
x
F

I

V

A

D

N

G

T

N

K

K

G

T

A

V

E

D

M

W

A

I

S

K

V

-

H

D

N

S

E

G

I

A

Q

K

Y

V

L

L

G

N

F

L

P
x
L

F

T

S

K

I

G

S

S

E

L

N

H

F

H

Q

L

M

E

R

K

N

Q

T

L

H

G

K

K

T

T

I

P

A

K

E

E

S

F

I

F

V

T

T

D

L

V

Q

S

E

F

I

V

L

I

E

E

I

Y

A

A

N

I

K

K

T

S

N

G

K

L

E

K

V

I

V

N

A

V

Y
|
Y

L

L

-
x
E

-

D

-

W

S

S

M

N

G

G

F

F

G

R

N

N

P

-

Y

-

G

-

D

-

P

-

W

-

N

S

V

P

D

D

I

Y

V

V

G

K

E

S

W

L

T

V

E

E

K

H

L

L

A

S

N

K

M

E

G

H

V

I

T

E

I

R

L

I

S

F

L

L

S

P

D

D

T
|
T

V

L

G

G

S

V

S

L

T

S

A

P

E

E

D

E

I

T

D

F

Y

Q

L

G

F

V

S

D

N

S

L

L

I

I

P

Q

K

K

Y

Y

P

P

N

D

I

I

E

H

F

F

G

E

A

F

H

H

L

G

H

H

T

N

T

D

P

Y

D

D

A

L

W

S

F

V

E

A

K

N

V

S

D

L

A

Q

A

A

Y

I

K

R

A

A

G

G

C

V

I

K

R

G

F

L

D

H

G

A

A

S

I

I

K

N

G

G

F

L

G

G

G

-

C

-

P

-

M

-

A

-

K

-

D

-

D

E

L

R

T

A

G

G

N

N

M

T

P

P

T

L

E

E

K

A

M

L

L

V

S

T

Y

T

F

I

-

H

T

D

A

K

N

S

K

N

A

S

A

K

T

T

N

N

V

I

Q

N

M

-

T

-

S

-

F

-

E

E

A

I

A

A

Y

I

N

T

E

E

A

A

L

S

K

R

I

L

F

V

N

E

F

V

Y

F

R16 (= R11) mutation R->K,Q: Loss of activity.
RD 16:17 (= RD 11:12) binding pyruvate
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 (= L75) 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 (≠ I77) mutation to A: 5-fold increase in Km for acetyl-CoA and 120-fold decrease in kcat.
L104 (≠ P99) 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 (vs. gap) 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)
26% identity, 61% coverage: 113:286/287 of query aligns to 112:272/311 of 3bliA

query
sites
3bliA

K

K

T

T

I

P

A

K

E

E

S

F

I

F

V

T

T

D

L

V

Q

S

E

F

I

V

L

I

E

E

I

Y

A

A

N

I

K

K

T

S

N

G

K

L

E

K

V

I

V

N

A

V

Y
|
Y

L

L

-
x
E

-

D

-

W

S

S

M

N

G

G

F

F

G

R

N

N

P

-

Y

-

G

-

D

-

P

-

W

-

N

S

V

P

D

D

I

Y

V

V

G

K

E

S

W

L

T

V

E

E

K

H

L

L

A

S

N

K

M

E

G

H

V

I

T

E

I

R

L

I

S

F

L

L

S
x
P

D

D

T
|
T

V

L

G

G

S

V

S

L

T

S

A

P

E

E

D

E

I

T

D

F

Y

Q

L

G

F

V

S

D

N

S

L

L

I

I

P

Q

K

K

Y

Y

P

P

N

D

I

I

E

H

F

F

G

E

A

F

H
|
H

L

G

H
|
H

T

N

T

D

P

Y

D

D

A

L

W

S

F

V

E

A

K

N

V

S

D

L

A

Q

A

A

Y

I

K

R

A

A

G

G

C

V

I

K

R

G

F

L

D

H

G

A

A

S

I

I

K

N

G

G

F

L

G

G

G

-

C

-

P

-

M

-

A

-

K

-

D

-

D

E

L

R

T

A

G

G

N

N

M

T

P

P

T

L

E

E

K

A

M

L

L

V

S

T

Y

T

F

I

-

H

T

D

A

K

N

S

K

N

A

S

A

K

T

T

N

N

V

I

Q

N

M

-

T

-

S

-

F

-

E

E

A

I

A

A

Y

I

N

T

E

E

A

A

L

S

K

R

I

L

F

V

N

E

F

V

Y

F

binding acetyl coenzyme *a: E140 (vs. gap)
binding pyruvic acid: Y138 (= Y139), P171 (≠ S175), T173 (= T177)
binding zinc ion: H201 (= H205), H203 (= H207)

Sites not aligning to the query:

6e1jA Crystal structure of methylthioalkylmalate synthase (bjumam1.1) from brassica juncea (see paper)
20% identity, 85% coverage: 11:255/287 of query aligns to 26:268/409 of 6e1jA

query
sites
6e1jA

R

R

D
|
D

A

G

M

E

Q
|
Q

G

S

I

P

K

G

M

A

F

A

I

L

P

T

T

P

E

P

Q

Q

K

K

V

I

Q

E

Y

I

I

A

Q

R

S

Q

L

L

L

A

R

K

C

L

G

R

F

V

D

D

T

I

L

M

D

E

F

V

G

G

S
x
F

F

P

V

V

S
|
S

P

S

K

E

A

E

-

E

I

F

P

E

Q

T

M

I

Q

Q

D

T

T

I

A

A

E

K

V

T

L

V

A

G

-

N

Q

E

L
x
V

D

D

L
x
E

S

E

E

T

T

G

K

Y

T

I

K

P

L

V

L

I

A

C

I

V

I
|
I

A

A

N
x
R

T

S

K

K

G

E

A

R

E

D

M

I

A

K

S

A

V

A

H

W

N

E

E

S

I

V

Q

K

Y

Y

L

A

G

K

F

R

P

P

-

R

-

I

-

V

-

I

F
|
F

S

T

I

S

S

T

E

S

N

D

F

I

Q

H

M

L

R

K

N

Y

T
x
K

H
x
L

K

K

T

M

I

T

A

R

E

E

S

E

I

V

V

V

T

D

L

M

Q

-

E

-

I

-

L

-

E

-

I

V

A

A

N

S

K

S

T

I

N

R

-

F

K

A

E

K

V

S

V

L

A

G

Y

F

L

E

S

D

M

I

G

E

F

F

G

G

N

C

P

E

Y

D

G

G

D

G

P

R

W

S

N

D

V

K

D

D

I

Y

V

I

G

C

E

T

W

V

T

F

E

E

K

E

L

A

A

I

N

K

M

A

G

G

V

A

T

T

I

T

L

L

S

A

L

C

S
x
P

D

D

T
|
T

V

V

G

G

S

I

S

N

T

M

A

P

E

H

D

E

I

Y

D

G

Y

K

L

L

F

V

S

R

N

Y

L

I

I

K

P

A

K

N

Y

T

P

P

N

G

I

I

E

D

-

D

-

V

-

I

F

F

G

S

A

A

H
|
H

L

C

H
|
H

T

N

T

D

P

L

D

G

A

V

W

A

F

T

E

A

K

N

V

T

D

I

A

A

A

G

Y

I

K

C

A

A

G

G

C

A

I

R

R

Q

F

V

D

E

G

V

A

T

I

I

K

N

G

G

F

I

G

G

G

-

C

-

P

-

M

-

A

-

K

-

D

-

D

E

L

R

T

S

G

G

N

N

M

A

P

P

T

L

E

E

K

E

M

V

L

V

binding coenzyme a: Q30 (= Q15), F60 (≠ S45), S63 (= S48), I95 (= I78), R97 (≠ N80), F121 (= F100), K132 (≠ T111), L133 (≠ H112)
binding 4-(methylsulfanyl)-2-oxobutanoic acid: P192 (≠ S175), T194 (= T177), H225 (= H205), H227 (= H207)
binding manganese (ii) ion: D27 (= D12), V82 (≠ L65), E84 (≠ L67), H225 (= H205), H227 (= H207)

Sites not aligning to the query:

binding coenzyme a: 322, 323, 324, 327, 331, 359, 362, 363

P11154 Pyruvate carboxylase 1; Pyruvic carboxylase 1; PCB 1; EC 6.4.1.1 from Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast) (see paper)
29% identity, 31% coverage: 149:237/287 of query aligns to 708:796/1178 of P11154

query
sites
P11154

G

G

D

K

P

K

W

Y

N

N

V

L

D

D

I

Y

V

Y

G

L

E

E

W

I

T

A

E

E

K

K

L

I

A

V

N

Q

M

M

G

G

V

T

T

H

I

I

L

L

S

G

L

I

S

K

D

D

T

M

V

A

G

G

S

T

S

M

T

K

A

P

E

A

D

A

I

A

D

K

Y

L

L

L

F

I

S

G

N

S

L

L

I

R

P

A

K

K

Y

Y

P

P

N

D

I

L

E

P

F

I

G

H

A

V

H

H

L

T

H

H

T

D

T

S

P

A

D

G

A

T

W

A

F

V

E

A

K

S

V

M

D

T

A

A

A

C

Y

A

K

L

A

A

G

G

C

A

I

D

R

V

F

V

D

D

G

V

A

A

I

I

K

N

G

S

F

M

G

S

G

G

Sites not aligning to the query:

1135 modified: N6-biotinyllysine

Query Sequence

>WP_091525706.1 NCBI__GCF_900115115.1:WP_091525706.1
MKPVKIIECPRDAMQGIKMFIPTEQKVQYIQSLLRCGFDTLDFGSFVSPKAIPQMQDTAE
VLAQLDLSETKTKLLAIIANTKGAEMASVHNEIQYLGFPFSISENFQMRNTHKTIAESIV
TLQEILEIANKTNKEVVAYLSMGFGNPYGDPWNVDIVGEWTEKLANMGVTILSLSDTVGS
STAEDIDYLFSNLIPKYPNIEFGAHLHTTPDAWFEKVDAAYKAGCIRFDGAIKGFGGCPM
AKDDLTGNMPTEKMLSYFTANKAATNVQMTSFEAAYNEALKIFNFYH

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