SitesBLAST

SitesBLAST – Find functional sites

SitesBLAST

Comparing BPHYT_RS02130 FitnessBrowser__BFirm:BPHYT_RS02130 to proteins with known functional sites using BLASTp with E ≤ 0.001.

Or try Sites on a Tree, PaperBLAST, Conserved Domains, or compare to all protein structures

Found 20 (the maximum) hits to proteins with known functional sites (download)

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)
56% identity, 95% coverage: 3:295/308 of query aligns to 29:321/325 of P35914

query
sites
P35914

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E37 (= E11) to K: in HMGCLD; activity lower than 5% respect to the wild-type; mutation to D: Normal activity.
R41 (= R15) to Q: in HMGCLD; loss of activity and of proton exchange; dbSNP:rs121964997; mutation to M: Reduced activity, and loss of proton exchange.
D42 (= D16) 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 (= K22) to N: in HMGCLD; abolishes almost all enzymatic activity
E72 (= E46) mutation to A: Loss of activity, and reduced affinity for metal cofactor and substrate.
S142 (= S116) to F: in HMGCLD; activity lower than 5% respect to the wild-type
C174 (= C148) to Y: in HMGCLD; activity lower than 5% respect to the wild-type; dbSNP:rs765475941
F192 (= F166) to S: in HMGCLD; activity lower than 5% respect to the wild-type
I200 (= I174) to F: in HMGCLD; activity lower than 5% respect to the wild-type
G203 (≠ A177) to E: in HMGCLD; complete loss of activity; dbSNP:rs1553131940
D204 (= D178) mutation to A: Reduced activity, and reduced affinity for metal cofactor and substrate.
H233 (= H207) to R: in HMGCLD; loss of activity; dbSNP:rs727503963; mutation to A: Loss of activity, and reduced proton exchange rate.
E279 (= E253) mutation to A: Reduced thermal stability, but normal activity.
D280 (= D254) 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)
56% identity, 95% coverage: 3:295/308 of query aligns to 2:294/296 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 (= R15), D15 (= D16), Q18 (= Q19), F49 (= F50), V50 (= V51), S51 (= S52), P52 (= P53), K53 (= K54), W54 (= W55), H61 (≠ G62), L79 (= L80), P81 (= P82), N82 (= N83), K84 (≠ R85), G85 (= G86), F100 (= F101), N111 (= N112), I112 (= I113), N113 (= N114), R122 (= R123), Y140 (≠ S141), S142 (= S143), T178 (= T179), H206 (= H207), H208 (= H209)
binding magnesium ion: D15 (= D16), H206 (= H207), H208 (= H209)

2cw6A Crystal structure of human hmg-coa lyase: insights into catalysis and the molecular basis for hydroxymethylglutaric aciduria (see paper)
56% identity, 95% coverage: 3:295/308 of query aligns to 2:294/296 of 2cw6A

query
sites
2cw6A

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binding 3-hydroxypentanedioic acid: R14 (= R15), Q18 (= Q19), F100 (= F101)
binding magnesium ion: D15 (= D16), H206 (= H207), H208 (= H209), N248 (= N249)

3mp5B Crystal structure of human lyase r41m in complex with hmg-coa (see paper)
56% identity, 95% coverage: 3:295/308 of query aligns to 2:294/296 of 3mp5B

query
sites
3mp5B

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M

L

N

E

G

G

L

L

G

G

I

I

E

H

T

T

G

G

I

V

D

N

L

L

A

Q

Q

K

V

L

A

E

I

A

G

G

D

N

F

F

I

I

S

C

T

Q

S

A

I

L

G

N

R

R

P

K

N

T

V

S

S

S

R

K

A

V

G

A

K

Q

A

A

binding 3-hydroxy-3-methylglutaryl-coenzyme a: D15 (= D16), Q18 (= Q19), S51 (= S52), P52 (= P53), K53 (= K54), W54 (= W55), H61 (≠ G62), L79 (= L80), F100 (= F101), N111 (= N112), I112 (= I113), N113 (= N114), R122 (= R123), Y140 (≠ S141), S142 (= S143), G176 (≠ A177), T178 (= T179), H206 (= H207), H208 (= H209), C239 (= C240)
binding magnesium ion: D15 (= D16), H206 (= H207), H208 (= H209)

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)
57% identity, 95% coverage: 3:295/308 of query aligns to 74:366/370 of Q8TB92

query
sites
Q8TB92

L

L

P

P

Q

E

Q

F

V

V

K

K

I

I

V

V

E

E

V

V

G

G

P

P

R
|
R

D

D

G

G

L

L

Q

Q

N

N

E

E

K

K

D

V

F

I

V

V

P

P

T

T

A

D

I

I

K

K

I

I

E

E

L

F

I

I

N

N

R

R

L

L

S

S

A

Q

A

T

G

G

F

L

R

S

N

V

V

I

E

E

A

V

A

T

S

S

F

F

V

V

S

S

P

S

K

R

W

W

V

V

P

P

Q

Q

M

M

A

A

D

D

G

H

A

T

D

E

V

V

M

M

A

K

G

G

I

I

E

H

R

Q

R

Y

P

P

G

G

T

V

I

R

Y

Y

S

P

V

V

L

L

T

T

P

P

N

N

L

L

R

Q

G

G

F

F

E

H

G

H

A

A

L

V

A

A

R

G

A

A

D

T

E

E

I

I

V

S

I

V

F

F

G

G

A

A

S

S

E

E

A

S

F

F

S

S

Q

K

K

K

N

N

I

I

N

N

C

C

S

S

I

I

A

E

E

E

S

S

I

M

D

G

R

K

F

F

V

E

P

E

V

V

A

V

Q

K

A

S

A

A

K

R

E

H

H

M

G

N

L

I

R

P

I

A

R

R

G

G

S

Y

V

V

S

S

C

C

A

A

L

L

G

G

C

C

P

P

Y

Y

Q

E

G

G

E

S

V

I

P

T

V

P

A

Q

S

K

V

V

V

T

D

E

V

V

V

S

Q

K

R

R

F
x
L

A

Y

A

G

L

M

G

G

C

C

D

Y

E

E

I

I

D

S

I

L

A

G

D

D

T

T

I

I

G

G

V

V

G

G

T

T

P

P

K

G

R

S

A

M

R

K

E

R

V

M

F

L

E

E

A

S

V

V

T

M

Q

K

V

E

F

I

P

P

R

P

E

G

R

A

L

L

S

A

G

V

H
|
H

F

C

H

H

D

D

T

T

Y

Y

G

G

Q

Q

A

A

L

L

A

A

N

N

I

I

Y

L

A

T

A

A

L

L

Q

Q

E

M

G

G

I

I

E

N

I

V

Y

V

H

D

A

S

S

A

V

V

A

S

G

G

L

L

G

G

C

C

P

P

Y

Y

A

A

K

K

G

G

A

A

T

S

G

G

N

N

V

V

A

A

T

T

E

E

D

D

V

L

L

I

Y

Y

L

M

M

L

N

N

G

G

L

L

G

G

I

L

E

N

T

T

G

G

I

V

D

N

L

L

A

Y

Q

K

V

V

V

M

A

E

I

A

G

G

D

D

F

F

I

I

S

C

T

K

S

A

I

V

G

N

R

K

P

T

N

T

V

N

S

S

R

K

A

V

G

A

K

Q

A

A

R86 (= R15) mutation to Q: Abolishes catalytic activity.
L237 (≠ F166) mutation to S: Abolishes catalytic activity.
H278 (= H207) 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)
52% identity, 97% coverage: 5:303/308 of query aligns to 2:300/301 of P13703

query
sites
P13703

Q

Q

Q

A

V

V

K

K

I

V

V

F

E

E

V

V

G

G

P

P

R

R

D

D

G

G

L

L

Q

Q

N

N

E

E

K

R

D

Q

F

P

V

L

P

S

T

V

A

A

I

A

K

R

I

V

E

G

L

L

I

I

N

G

R

E

L

L

S

A

A

G

A

T

G

G

F

L

R

R

N

H

V

I

E

E

A

A

A

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

G

S

A

D

D

E

V

V

M

L

A

R

G

Q

I

L

E

P

R

S

R

N

P

D

G

G

T

V

I

S

Y

Y

S

T

V

A

L

L

T

V

P

P

N

N

L

R

R

Q

G

G

F

F

E

E

G

A

A

A

L

Q

A

R

A

A

R

G

A

C

D

R

E

E

I

V

V

A

I

V

F

F

G

A

A

A

S

S

E

E

A

A

F

F

S

S

Q

R

K

N

N

N

I

I

N

N

C

C

S

S

I

I

A

D

E

E

S

S

I

F

D

E

R

R

F

F

V

T

P

P

V

V

A

L

Q

R

A

A

K

N

E

E

H

A

G

S

L

I

R

R

I

V

R

R

G

G

S

Y

V

V

S

S

C

C

A

V

L

L

G

G

C

C

P

P

Y

F

Q

S

G

G

E

A

V

V

P

A

V

P

A

E

S

A

V

V

V

A

D

K

V

V

V

A

Q

R

R

R

F

L

A

Y

A

E

L

L

G

G

C

C

D

Y

E

E

I

I

D

S

I

L

A

G

D

D

T

T

I

I

G

G

V

A

G

G

T

R

P

P

K

D

R

E

A

T

R

A

E

Q

V

L

F

F

E

E

A

L

V

C

T

A

Q

R

V

Q

F

L

P

P

R

V

E

A

R

A

L

L

S

A

G

G

H

H

F

F

H

H

D

D

T

T

Y

W

G

G

Q

M

A

A

L

I

A

A

N

N

I

V

Y

H

A

A

L

L

Q

A

E

Q

G

G

I

V

E

R

I

T

Y

F

H

D

A

S

S

S

V

V

A

A

G

G

L

L

G

G

C
|
C

P

P

Y

Y

A

S

K

P

G

G

A

A

T

S

G

G

N

N

V

V

A

A

T

T

E

E

D

D

V

L

L

L

Y

Y

L

L

M

L

N

H

G

G

L

L

G

G

I

Y

E

S

T

T

G

G

I

V

D

D

L

L

A

E

Q

A

V

V

V

A

A

Q

I

V

G

G

D

V

F

R

I

I

S

S

T

A

S

Q

I

L

G

G

R

T

P

A

N

N

V

R

S

S

R

R

A

A

G

G

K

L

A

A

L

L

L

A

A

A

K

R

A

S

R

A

S

R

E

E

C237 (= C240) active site

1ydnA Crystal structure of the hmg-coa lyase from brucella melitensis, northeast structural genomics target lr35. (see paper)
54% identity, 89% coverage: 5:279/308 of query aligns to 2:276/283 of 1ydnA

query
sites
1ydnA

Q

E

Q

H

V

V

K

E

I

I

V

V

E

E

V

M

G

A

P

A

R

R

D
|
D

G

G

L

L

Q

Q

N

N

E

E

K

K

D

R

F

F

V

V

P

P

T

T

A

A

I

D

K

K

I

I

E

A

L

L

I

I

N

N

R

R

L

L

S

S

A

D

A

C

G

G

F

Y

R

A

N

R

V

I

E

E

A

A

A

T

S

S

F

F

V

V

S

S

P

P

K

K

W

W

V

V

P

P

Q

Q

M

L

A

A

D

D

G

S

A

R

D

E

V

V

M

M

A

A

G

G

I

I

E

R

R

R

R

A

P

D

G

G

T

V

I

R

Y

Y

S

S

V

V

L

L

T

V

P

P

N

N

L

M

R

K

G

G

F

Y

E

E

G

A

A

A

L

A

A

A

R

H

A

A

D

D

E

E

I

I

V

A

I

V

F

F

G

I

A

S

A

A

S

S

E

E

A

G

F

F

S

S

Q

K

K

A

N

N

I

I

N

N

C

C

S

T

I

I

A

A

E

E

S

S

I

I

D

E

R

R

F

L

V

S

P

P

V

V

A

I

Q

G

A

A

K

I

E

N

H

D

G

G

L

L

R

A

I

I

R

R

G

G

S

Y

V

V

S

S

C

C

A

V

L

V

G

E

C

C

P

P

Y

Y

Q

D

G

G

E

P

V

V

P

T

V

P

A

Q

S

A

V

V

V

A

D

S

V

V

V

T

Q

E

R

Q

F

L

A

F

A

S

L

L

G

G

C

C

D

H

E

E

I

V

D

S

I

L

A

G

D

D

T

T

I

I

G

G

V

R

G

G

T

T

P

P

K

D

R

T

A

V

R

A

E

A

V

M

F

L

E

D

A

A

V

V

T

L

Q

A

V

I

F

A

P

P

R

A

E

H

R

S

L

L

S

A

G

G

H
|
H

F

Y

H
|
H

D

D

T

T

Y

G

G

G

Q

R

A

A

L

L

A

D

N

N

I

I

Y

R

A

V

A

S

L

L

Q

E

E

K

G

G

I

L

E

R

I

V

Y

F

H

D

A

A

S

S

V

V

A

G

G

G

L

L

G

G

C

C

P

P

Y

F

A

A

K

P

G

G

A

A

T

K

G

G

N
|
N

V

V

A

D

T

T

E

V

D

A

V

V

L

V

Y

E

L

M

M

L

N

H

G

E

L

M

G

G

I

F

E

E

T

T

G

G

I

L

D

D

L

L

A

D

Q

R

V

L

V

R

A

S

I

A

G

G

D

L

F

F

binding calcium ion: D13 (= D16), H204 (= H207), H206 (= H209), N246 (= N249)

6ndsA Structure of an hmg-coa lyase from acenitobacter baumannii in complex with coenzyme a and 3-methylmalate
37% identity, 93% coverage: 9:295/308 of query aligns to 10:295/305 of 6ndsA

query
sites
6ndsA

I

V

V

Q

E

E

V

V

G

S

P

P

R

R

D
|
D

G

G

L

L

Q
|
Q

N

I

E

E

K

P

D

T

F

W

V

V

P

P

T

T

A

D

I

K

K

K

I

I

E

D

L

L

I

I

N

N

R

Q

L

L

S

S

A

T

A

M

G

G

F

F

R

S

N

R

V

I

E

E

A

A

A

G

S

S

F
|
F

V
|
V

S
|
S

P
|
P

K

K

W
x
A

V
x
I

P

P

Q

N

M

L

A

R

D

D

G

G

A

E

D

E

V

V

M

F

A

T

G

G

I

I

E

T

R

R

R

H

P

K

G

D

T

I

I

I

Y

Y

S

V

V

G

L
|
L

T

I

P
|
P

N
|
N

L

L

R
x
K

G
|
G

F

A

E

L

G
x
R

A

A

L

V

A

E

A

A

R

N

A

A

D

N

E

E

I

L

V

N

I

L

F

V

G

L

A

S

A

A

S

S

E

Q

A

T

F

H

S

N

Q

L

K

A

N
|
N

I
x
M

N
x
R

C

M

S

T

I

K

A

A

E

Q

S

S

I

F

D

A

R

G

F

F

V

T

P

E

V

I

A

V

Q

E

A

Q

A

L

K

Q

E

G

H

K

G

-

L

T

R

Q

I

F

R

N

G

G

S

T

V

V

S

A

C

T

A

T

L

F

G

G

C

C

P

P

Y

F

Q

E

G

G

E

K

V

I

P

S

V

E

A

R

S

E

V

V

V

F

D

S

V

L

V

V

Q

E

R

H

F

Y

A

L

A

K

L

L

G

G

C

I

D

H

E

N

I

I

D

T

I

L

A

A

D

D

T

T

I

T

G

G

V

M

G

A

T

N

P

P

K

V

R

Q

A

V

R

K

E

R

V

I

F

V

E

S

A

H

V

V

T

L

Q

S

V

L

F

I

P

S

R

P

E

E

R

Q

L

L

S

T

G

L

H
|
H

F

F

H
|
H

D

N

T

T

Y

R

G

G

Q

L

A

G

L

L

A

T

N

N

I

V

Y

L

A

A

L

Y

Q

E

E

V

G

G

I

A

E

R

I

R

Y

F

H

D

A

A

S

A

V

L

A

G

G

G

L

L

G

G

C
|
C

P

P

Y

F

A

A

K

P

G

G

A

A

T

S

G

G

N

N

V

I

A

C

T

T

E

E

D

D

V

L

L

V

Y

N

L

M

M

C

N

E

G

E

L

I

G

G

I

I

E

P

T

T

G

T

I

I

D

D

L

L

A

D

Q

A

V

L

V

I

A

Q

I

L

G

S

D

R

F

T

I

L

S

P

T

A

S

L

I

L

G

G

R

H

P

D

N

T

V

P

S

S

R

Q

A

L

G

A

K

K

A

A

binding coenzyme a: Q20 (= Q19), F51 (= F50), V52 (= V51), S53 (= S52), P54 (= P53), A56 (≠ W55), I57 (≠ V56), L81 (= L80), P83 (= P82), N84 (= N83), K86 (≠ R85), G87 (= G86), R90 (≠ G89), N113 (= N112), M114 (≠ I113), R115 (≠ N114), C240 (= C240)
binding zinc ion: D17 (= D16), H207 (= H207), H209 (= H209)

6ktqA Crystal structure of catalytic domain of homocitrate synthase from sulfolobus acidocaldarius (sahcs(dram)) in complex with alpha- ketoglutarate/zn2+/coa (see paper)
28% identity, 77% coverage: 2:238/308 of query aligns to 17:247/399 of 6ktqA

query
sites
6ktqA

A

S

L

L

P

H

Q

M

Q

K

V

V

K

G

I

I

V

L

E

D

V

S

G

T

P

L

R
|
R

D
x
E

G

G

L

E

Q

Q

N

T

E

P

K

G

D

V

F

V

V

F

P

T

T

T

A

D

I

Q

K

R

I

V

E

E

L

I

I

A

N

K

R

A

L

L

S

S

A

D

A

I

G

G

F

V

R

Q

N

M

V

I

E

E

A

A

A

G

S
x
H

F

-

V

-

S

-

P

P

K

A

W
x
V

V

S

P

P

Q

D

M

I

A

Y

D

E

G

G

A

I

D

R

V

R

M

I

A

I

G

K

I

L

E

-

R

K

R

R

P

E

G

G

T

V

I

I

Y

K

S

S

V

E

L

I

T

V

P

A

N
x
H

L

S

R
|
R

G
x
A

F
x
V

E

K

G

R

A

D

L

I

A

E

A

V

-

G

-

A

-

E

-

I

R

E

A

A

D

D

E

R

I

I

V

A

I

I

F
|
F

G
x
Y

A

G

A

I

S

S

E

D

A

T

F

H

S

L

Q

K

K

A

N
x
K

I
x
H

N

H

C

T

S

T

I

R

A

D

E

E

S

A

I

L

D

R

R

S

F

I

V

A

P

E

V

T

A

V

Q

S

A

Y

A

A

K

K

E

S

H

H

G

G

L

V

R

K

I

V

R
|
R

G

F

S
x
T

V

A

S
x
E

C

D

A

A

L

T

G

R

C

A

P

D

Y

Y

Q

Q

G

-

E

-

V

-

P

-

V

-

A

-

S

Y

V

L

D

E

V

V

V

I

Q

K

R

T

F

V

A

R

A

D

L

A

G

G

C

A

D

D

E

R

I

V

D
x
S

I

I

A
|
A

D

D

T
|
T

I

V

G

G

V

V

G

L

T

Y

P

P

K

S

R

R

A

T

R

R

E

E

V

L

F

F

E

K

A

D

V

L

T

T

Q

S

V

R

F

F

P

P

R

D

E

I

R

E

L

F

S

D

G

I

H
|
H

F

A

H
|
H

D

N

T

D

Y

L

G

G

Q

M

A

A

L

V

A

A

N

N

I

V

Y

L

A

A

L

A

Q

E

E

G

G

G

I

A

E

T

I

I

Y

I

H
|
H

A

T

S

T

V

L

A

N

G

G

L

L

G

G

binding 2-oxoglutaric acid: R30 (= R15), E31 (≠ D16), H94 (≠ N83), R154 (= R139), T156 (≠ S141), E158 (≠ S143), S184 (≠ D175), A186 (= A177), T188 (= T179), H216 (= H207), H218 (= H209), H240 (= H231)
binding coenzyme a: H64 (≠ S49), V67 (≠ W55), R96 (= R85), A97 (≠ G86), V98 (≠ F87), F116 (= F101), Y117 (≠ G102), K127 (≠ N112), H128 (≠ I113), E158 (≠ S143)
binding zinc ion: E31 (≠ D16), H216 (= H207), H218 (= H209)

2nx9B Crystal structure of the carboxyltransferase domain of the oxaloacetate decarboxylase na+ pump from vibrio cholerae (see paper)
28% identity, 49% coverage: 129:280/308 of query aligns to 133:273/453 of 2nx9B

query
sites
2nx9B

Q

Q

A

A

A

V

K

K

E

K

H

M

G

G

L

A

R

H

I

A

R

Q

G

G

S

T

V

L

S

-

C

C

A

Y

L

T

G

T

C

S

P

P

Y

V

Q

H

G

N

E

-

V

-

P

-

V

L

A

Q

S

T

V

W

V

V

D

D

V

V

V

A

Q

Q

R

Q

F

L

A

A

A

E

L

L

G

G

C

V

D

D

E

S

I

I

D

A

I

L

A
x
K

D

D

T

M

I

A

G

G

V

I

G

L

T

T

P

P

K

Y

R

A

A

A

R

E

E

E

V

L

F

V

E

S

A

T

V

L

T

K

Q

K

V

Q

F

V

P

D

R

V

E

E

R

-

L

L

S

H

G

L

H
|
H

F

C

H
|
H

D

S

T

T

Y

A

G

G

Q

L

A

A

L

D

A

M

N

T

I

L

Y

L

A

K

A

A

L

I

Q

E

E

A

G

G

I

V

E

D

I

R

Y

V

H

D

A

T

S

A

V

I

A

S

G

S

L

M

G

S

G

G

C

T

P

-

Y

-

A

-

K

-

G

-

A

-

T

Y

G

G

N

H

V

P

A

A

T

T

E

E

D

S

V

L

L

V

Y

A

L

T

M

L

N

Q

G

G

L

T

G

G

I

Y

E

D

T

T

G

G

I

L

D

D

L

I

A

A

Q

K

V

L

V

E

A

Q

I

I

G

A

D

A

F

Y

I

F

active site: K177 (≠ A177), H206 (= H207), H208 (= H209)
binding zinc ion: H206 (= H207), H208 (= H209)

Sites not aligning to the query:

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

3rmjB Crystal structure of truncated alpha-isopropylmalate synthase from neisseria meningitidis (see paper)
32% identity, 38% coverage: 170:287/308 of query aligns to 161:279/308 of 3rmjB

query
sites
3rmjB

G

G

C

A

D

T

E

T

I

I

D

N

I

I

A

P

D

D

T

T

I

V

G

G

V

Y

G

S

T

I

P

P

K

Y

R

K

A

T

R

E

E

E

V

F

F

F

E

R

A

E

V

L

T

I

Q

A

V

K

F

T

P

P

-

N

-

G

R

K

E

V

R

V

L

W

S

S

G

A

H
|
H

F

C

H
|
H

D

N

T

D

Y

L

G

G

Q

L

A

A

L

V

A

A

N

N

I

S

Y

L

A

A

L

L

Q

K

E

G

G

G

I

A

E

R

I

Q

Y

V

H

E

A

C

S

T

V

V

A

N

G

G

L

L

G

G

G

-

C

-

P

-

Y

-

A

-

K

-

G

E

A

R

T

A

G

G

N
|
N

V

A

A

S

T

V

E

E

D

E

V

I

L

V

Y

M

L

A

M

L

-

K

-

V

-

R

-

H

N

D

G

L

L

F

G

G

I

L

E

E

T

T

G

G

I

I

D

D

L

T

A

T

Q

Q

V

I

V

V

A

P

I

S

G

S

D

K

F

L

I

V

S

S

T

T

S

I

I

T

G

G

R

Y

P

P

binding manganese (ii) ion: H201 (= H207), H203 (= H209), N237 (= N249)

Sites not aligning to the query:

active site: 16
binding manganese (ii) ion: 13

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)
32% identity, 38% coverage: 170:287/308 of query aligns to 164:282/517 of Q9JZG1

query
sites
Q9JZG1

G

G

C

A

D

T

E

T

I

I

D

N

I

I

A

P

D

D

T

T

I

V

G

G

V

Y

G

S

T

I

P

P

K

Y

R

K

A

T

R

E

E

E

V

F

F

F

E

R

A

E

V

L

T

I

Q

A

V

K

F

T

P

P

-

N

-

G

R

K

E

V

R

V

L

W

S

S

G

A

H
|
H

F

C

H
|
H

D

N

T

D

Y

L

G

G

Q

L

A

A

L

V

A

A

N

N

I

S

Y

L

A

A

L

L

Q

K

E

G

G

G

I

A

E

R

I

Q

Y

V

H

E

A

C

S

T

V

V

A

N

G

G

L

L

G

G

G

-

C

-

P

-

Y

-

A

-

K

-

G

E

A

R

T

A

G

G

N
|
N

V

A

A

S

T

V

E

E

D

E

V

I

L

V

Y

M

L

A

M

L

-

K

-

V

-

R

-

H

N

D

G

L

L

F

G

G

I

L

E

E

T

T

G

G

I

I

D

D

L

T

A

T

Q

Q

V

I

V

V

A

P

I

S

G

S

D

K

F

L

I

V

S

S

T

T

S

I

I

T

G

G

R

Y

P

P

H204 (= H207) binding
H206 (= H209) binding
N240 (= N249) binding

Sites not aligning to the query:

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

3ivtB Homocitrate synthase lys4 bound to 2-og (see paper)
23% identity, 75% coverage: 9:238/308 of query aligns to 32:250/400 of 3ivtB

query
sites
3ivtB

I

I

V

I

E

E

V

S

G

T

P

L

R
|
R

D
x
E

G

G

L

E

Q
|
Q

N

F

E

A

K

N

D

A

F

F

V

F

P

D

T

T

A

E

I

K

K

K

I

I

E

Q

L

I

I

A

N

K

R

A

L

L

S

D

A

N

A

F

G

G

F

V

R

D

N

Y

V

I

E

E

A

L

A

T

S

S

F

P

V

V

S

A

P

S

K

E

W

Q

V

S

P

R

Q

Q

M

D

A

C

D

E

G

-

A

A

D

I

V

C

M

K

A

L

G

G

I

L

E

K

R

C

R

K

P

-

G

-

T

-

I

I

Y

L

S

T

V
x
H

L

I

T

R

P

C

N

H

L

M

R

D

G

D

F

A

E

R

G

V

A

A

L

V

A

E

A

T

R

G

A

V

D

D

E

G

I

V

V

D

I

V

F
x
V

G

I

A

G

A

T

S

S

E

Q

A

Y

F

L

S

R

Q

K

K

Y

N

S

I

H

N

G

C

K

S

D

I

M

A

T

E

Y

S

I

I

I

D

D

R

S

F

A

V

T

P

E

V

V

A

I

Q

N

A

F

A

V

K

K

E

S

H

K

G

G

L

I

R

E

I

V

R
|
R

G

F

S
|
S

V

S

S

E

C

D

A

S

L

F

G

R

C

-

P

-

Y

-

Q

-

G

-

E

-

V

-

P

-

V

-

A

S

S

D

V

L

V

V

D

D

V

L

Q

S

R

L

F

Y

A

K

A

A

-

V

-

D

-

K

L

I

G

G

C

V

D

N

E

R

I

V

D

G

I

I

A
|
A

D

D

T
|
T

I

V

G

G

V

C

G

A

T

T

P

P

K

R

R

Q

A

V

R

Y

E

D

V

L

F

I

E

R

A

T

V

L

T

R

Q

G

V

V

F

V

P

S

R

C

E

D

R

-

L

I

S

E

G

C

H
|
H

F

F

H
|
H

D

N

T

D

Y

T

G

G

Q

M

A

A

L

I

A

A

N

N

I

A

Y

Y

A

C

A

A

L

L

Q

E

E

A

G

G

I

A

E

T

I

H

Y

I

H

D

A

T

S

S

V

I

A

L

G

G

L

I

G

G

active site: Q42 (= Q19)
binding 2-oxoglutaric acid: R38 (= R15), E39 (≠ D16), H98 (≠ V79), V120 (≠ F101), R158 (= R139), S160 (= S141), A190 (= A177), T192 (= T179), H219 (= H207), H221 (= H209)
binding zinc ion: E39 (≠ D16), H219 (= H207), H221 (= H209)

3mi3A Homocitrate synthase lys4 bound to lysine (see paper)
27% identity, 41% coverage: 113:238/308 of query aligns to 103:221/370 of 3mi3A

query
sites
3mi3A

I

I

N

G

C

T

S

S

I

M

A

T

E

Y

S

I

I

I

D

D

R

S

F

A

V

T

P

E

V

V

A

I

Q

N

A

F

A

V

K

K

E

S

H

K

G

G

L

I

R

E

I

V

R

R

G

F

S
|
S

V

S

S

E

C

D

A

S

L

F

G

R

C

-

P

-

Y

-

Q

-

G

-

E

-

V

-

P

-

V

-

A

S

S

D

V

L

V

V

D

D

V

L

Q

S

R

L

F

Y

A

K

A

A

-

V

-

D

-

K

L

I

G

G

C

V

D

N

E

R

I

V

D

G

I

I

A
|
A

D

D

T
|
T

I

V

G

G

V

C

G

A

T

T

P

P

K

R

R

Q

A

V

R

Y

E

D

V

L

F

I

E

R

A

T

V

L

T

R

Q

G

V

V

F

V

P

S

R

C

E

D

R

-

L

I

S
x
E

G

C

H
|
H

F

F

H
|
H

D

N

T

D

Y

T

G

G

Q

M

A

A

L

I

A

A

N

N

I

A

Y

Y

A

C

A

A

L

L

Q

E

E

A

G

G

I

A

E

T

I

H

Y

I

H

D

A

T

S

S

V

I

A

L

G

G

L

I

G

G

binding lysine: S131 (= S141), A161 (= A177), T163 (= T179), E188 (≠ S205), H190 (= H207), H192 (= H209)
binding zinc ion: H190 (= H207), H192 (= H209)

Sites not aligning to the query:

O87198 Homocitrate synthase; HCS; EC 2.3.3.14 from Thermus thermophilus (strain ATCC BAA-163 / DSM 7039 / HB27) (see paper)
25% identity, 76% coverage: 5:238/308 of query aligns to 2:226/376 of O87198

query
sites
O87198

Q

R

Q

E

V

W

K

K

I

I

V

I

E

D

V

S

G

T

P

L

R
|
R

D
x
E

G

G

L

E

Q

Q

N

F

E

E

K

K

D

A

F

N

V

F

P

S

T

T

A

Q

I

D

K

K

I

V

E

E

L

I

I

A

N

K

R

A

L

L

S

D

A

E

A

F

G

G

F

I

R

E

N

Y

V

I

E

E

A

V

A

T

S

T

F

-

V

-

S

-

P

P

K

V

W

A

V

S

P

P

Q

Q

M

S

A

R

D

K

G

D

A

A

D

E

V

V

M

L

A

A

G

S

I

L

E

-

R

-

P

-

G

G

T

L

I

K

Y

A

S

K

V

V

L

V

T

T

P
x
H

N

I

L

Q

R

C

G

R

F

L

E

D

G

A

A

A

L

K

A

V

A

A

R

V

A

E

D

T

E

G

I

V

-

Q

-

G

-

I

-
x
D

V

L

I

L

F

F

G

G

A

T

A

S

S

K

-

Y

-

L

E

R

A

A

F

A

S

H

Q

G

K

R

N

D

I

I

N

P

C

R

S

I

I

I

A

E

E

E

S

A

I

K

D

E

R

V

F

I

V

A

P

Y

V

I

A

R

Q

E

A

A

K

P

E

H

H

-

G

-

L

V

R

E

I

V

R
|
R

G

F

S
|
S

V

A

S

E

C

D

A

T

L

F

G

R

C

S

P

E

Y

E

Q

Q

G

D

E

L

V

L

P

A

V

V

A

Y

S

E

V

A

V

V

D

-

V

-

Q

-

R

-

F

-

A

-

A

A

L

P

G

Y

C

V

D

D

E

R

I

V

D

G

I

L

A

A

D

D

T
|
T

I

V

G

G

V

V

G

A

T

T

P

P

K

R

R

Q

A

V

R

Y

E

A

V

L

F

V

E

R

A

E

V

V

T

R

Q

R

V

V

F

V

-

G

P

P

R

R

E

V

R

D

L

I

S

E

G

F

H
|
H

F

G

H
|
H

D

N

T

D

Y

T

G

G

Q

C

A

A

L

I

A

A

N

N

I

A

Y

Y

A

E

A

A

L

I

Q

E

E

A

G

G

I

A

E

T

I

H

Y

V

H

D

A

T

S

T

V

I

A

L

G

G

L

I

G

G

R12 (= R15) binding
E13 (≠ D16) binding
H72 (≠ P82) binding ; 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 (vs. gap) binding
R133 (= R139) binding
S135 (= S141) binding
T166 (= T179) binding ; binding
H195 (= H207) binding
H197 (= H209) binding

3ivsA Homocitrate synthase lys4 (see paper)
27% identity, 38% coverage: 121:238/308 of query aligns to 109:219/364 of 3ivsA

query
sites
3ivsA

I

I

D

D

R

S

F

A

V

T

P

E

V

V

A

I

Q

N

A

F

A

V

K

K

E

S

H

K

G

G

L

I

R

E

I

V

R

R

G

F

S

S

V

S

S

E

C

D

A

S

L

F

G

R

C

-

P

-

Y

-

Q

-

G

-

E

-

V

-

P

-

V

-

A

S

S

D

V

L

V

V

D

D

V

L

Q

S

R

L

F

Y

A

K

A

A

-

V

-

D

-

K

L

I

G

G

C

V

D

N

E

R

I

V

D

G

I

I

A

A

D

D

T

T

I

V

G

G

V

C

G

A

T

T

P

P

K

R

R

Q

A

V

R

Y

E

D

V

L

F

I

E

R

A

T

V

L

T

R

Q

G

V

V

F

V

P

S

R

C

E

D

R

-

L

I

S
x
E

G

C

H
|
H

F

F

H
|
H

D

N

T

D

Y

T

G

G

Q

M

A

A

L

I

A

A

N

N

I

A

Y

Y

A

C

A

A

L

L

Q

E

E

A

G

G

I

A

E

T

I

H

Y

I

H
x
D

A

T

S

S

V

I

A

L

G

G

L

I

G

G

binding cobalt (ii) ion: H188 (= H207), H190 (= H209)
binding magnesium ion: E186 (≠ S205), D212 (≠ H231)

Sites not aligning to the query:

active site: 24
binding cobalt (ii) ion: 21

2zyfA Crystal structure of homocitrate synthase from thermus thermophilus complexed with magnesuim ion and alpha-ketoglutarate (see paper)
25% identity, 76% coverage: 5:238/308 of query aligns to 2:220/314 of 2zyfA

query
sites
2zyfA

Q

R

Q

E

V

W

K

K

I

I

V

I

E

D

V

S

G

T

P

L

R
|
R

D
x
E

G

G

L

E

Q
|
Q

N

F

E

E

K

K

D

A

F

N

V

F

P

S

T

T

A

Q

I

D

K

K

I

V

E

E

L

I

I

A

N

K

R

A

L

L

S

D

A

E

A

F

G

G

F

I

R

E

N

Y

V

I

E

E

A

V

A

T

S

T

F

-

V

-

S

-

P

P

K

V

W

A

V

S

P

P

Q

Q

M

S

A

R

D

K

G

D

A

A

D

E

V

V

M

L

A

A

G

S

I

L

E

-

R

-

P

-

G

G

T

L

I

K

Y

A

S

K

V

V

L

V

T

T

P
x
H

N

I

L

Q

R

C

G

R

F

L

E

D

G

A

A

A

L

K

A

V

A

A

R

V

A

E

D

T

E

G

I

V

-

Q

-

G

-

I

-

D

V

L

I
x
L

F

F

G

G

A

T

A

S

S

K

E

-

A

-

F

-

S

-

Q

G

K

R

N

D

I

I

N

P

C

R

S

I

I

I

A

E

E

E

S

A

I

K

D

E

R

V

F

I

V

A

P

Y

V

I

A

R

Q

E

A

A

K

P

E

H

H

-

G

-

L

V

R

E

I

V

R
|
R

G

F

S
|
S

V

A

S

E

C

D

A

T

L

F

G

R

C

S

P

E

Y

E

Q

Q

G

D

E

L

V

L

P

A

V

V

A

Y

S

E

V

A

V

V

D

-

V

-

Q

-

R

-

F

-

A

-

A

A

L

P

G

Y

C

V

D

D

E

R

I

V

D

G

I

L

A
|
A

D

D

T
|
T

I

V

G

G

V

V

G

A

T

T

P

P

K

R

R

Q

A

V

R

Y

E

A

V

L

F

V

E

R

A

E

V

V

T

R

Q

R

V

V

F

V

-

G

P

P

R

R

E

V

R

D

L

I

S

E

G

F

H
|
H

F

G

H
|
H

D

N

T

D

Y

T

G

G

Q

C

A

A

L

I

A

A

N

N

I

A

Y

Y

A

E

A

A

L

I

Q

E

E

A

G

G

I

A

E

T

I

H

Y

V

H

D

A

T

S

T

V

I

A

L

G

G

L

I

G

G

active site: Q16 (= Q19)
binding 2-oxoglutaric acid: R12 (= R15), H72 (≠ P82), L94 (≠ I100), R127 (= R139), S129 (= S141), A158 (= A177), T160 (= T179), H189 (= H207), H191 (= H209)
binding magnesium ion: E13 (≠ D16), H189 (= H207), H191 (= H209)

2ztjA Crystal structure of homocitrate synthase from thermus thermophilus complexed with alpha-ketoglutarate (see paper)
25% identity, 76% coverage: 5:238/308 of query aligns to 2:218/312 of 2ztjA

query
sites
2ztjA

Q

R

Q

E

V

W

K

K

I

I

V

I

E

D

V

S

G

T

P

L

R
|
R

D
x
E

G

G

L

E

Q
|
Q

N

F

E

E

K

K

D

A

F

N

V

F

P

S

T

T

A

Q

I

D

K

K

I

V

E

E

L

I

I

A

N

K

R

A

L

L

S

D

A

E

A

F

G

G

F

I

R

E

N

Y

V

I

E

E

A

V

A

T

S

T

F

-

V

-

S

-

P

P

K

V

W

A

V

S

P

P

Q

Q

M

S

A

R

D

K

G

D

A

A

D

E

V

V

M

L

A

A

G

S

I

L

E

-

R

-

P

-

G

G

T

L

I

K

Y

A

S

K

V

V

L

V

T

T

P
x
H

N

I

L

Q

R

C

G

R

F

L

E

D

G

A

A

A

L

K

A

V

A

A

R

V

A

E

D

T

E

G

I

V

-

Q

-

G

-

I

-

D

V

L

I
x
L

F

F

G

G

A

T

A

G

S

-

E

-

A

-

F

-

S

-

Q

-

K

R

N

D

I

I

N

P

C

R

S

I

I

I

A

E

E

E

S

A

I

K

D

E

R

V

F

I

V

A

P

Y

V

I

A

R

Q

E

A

A

K

P

E

H

H

-

G

-

L

V

R

E

I

V

R
|
R

G

F

S
|
S

V

A

S

E

C

D

A

T

L

F

G

R

C

S

P

E

Y

E

Q

Q

G

D

E

L

V

L

P

A

V

V

A

Y

S

E

V

A

V

V

D

-

V

-

Q

-

R

-

F

-

A

-

A

A

L

P

G

Y

C

V

D

D

E

R

I

V

D

G

I

L

A
|
A

D

D

T
|
T

I

V

G

G

V

V

G

A

T

T

P

P

K

R

R

Q

A

V

R

Y

E

A

V

L

F

V

E

R

A

E

V

V

T

R

Q

R

V

V

F

V

-

G

P

P

R

R

E

V

R

D

L

I

S

E

G

F

H
|
H

F

G

H
|
H

D

N

T

D

Y

T

G

G

Q

C

A

A

L

I

A

A

N

N

I

A

Y

Y

A

E

A

A

L

I

Q

E

E

A

G

G

I

A

E

T

I

H

Y

V

H

D

A

T

S

T

V

I

A

L

G

G

L

I

G

G

active site: Q16 (= Q19)
binding 2-oxoglutaric acid: R12 (= R15), E13 (≠ D16), H72 (≠ P82), L94 (≠ I100), R125 (= R139), S127 (= S141), A156 (= A177), T158 (= T179), H187 (= H207), H189 (= H209)
binding copper (ii) ion: E13 (≠ D16), H187 (= H207), H189 (= H209)

3a9iA Crystal structure of homocitrate synthase from thermus thermophilus complexed with lys (see paper)
25% identity, 76% coverage: 5:238/308 of query aligns to 1:219/347 of 3a9iA

query
sites
3a9iA

Q

R

Q

E

V

W

K

K

I

I

V

I

E

D

V

S

G

T

P

L

R
|
R

D
x
E

G

G

L

E

Q

Q

N

F

E

E

K

K

D

A

F

N

V

F

P

S

T

T

A

Q

I

D

K

K

I

V

E

E

L

I

I

A

N

K

R

A

L

L

S

D

A

E

A

F

G

G

F

I

R

E

N

Y

V

I

E

E

A

V

A

T

S

T

F

-

V

-

S

-

P

P

K

V

W

A

V

S

P

P

Q

Q

M

S

A

R

D

K

G

D

A

A

D

E

V

V

M

L

A

A

G

S

I

L

E

-

R

-

P

-

G

G

T

L

I

K

Y

A

S

K

V

V

L

V

T

T

P

H

N

I

L

Q

R

C

G

R

F

L

E

D

G

A

A

A

L

K

A

V

A

A

R

V

A

E

D

T

E

G

I

V

-

Q

-

G

-

I

-
x
D

V

L

I
x
L

F

F

G

G

A

T

A

S

S

K

E

-

A

-

F

-

S

-

Q

Y

K

L

N

D

I

I

N

P

C

R

S

I

I

I

A

E

E

E

S

A

I

K

D

E

R

V

F

I

V

A

P

Y

V

I

A

R

Q

E

A

A

K

P

E

H

H

-

G

-

L

V

R

E

I

V

R

R

G

F

S
|
S

V

A

S

E

C

D

A

T

L

F

G

R

C

S

P

E

Y

E

Q

Q

G

D

E

L

V

L

P

A

V

V

A

Y

S

E

V

A

V

V

D

-