SitesBLAST

SitesBLAST – Find functional sites

SitesBLAST

Comparing PP_1791 FitnessBrowser__Putida:PP_1791 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)

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)
32% identity, 44% coverage: 4:240/534 of query aligns to 14:244/347 of Q53WI0

query
sites
Q53WI0

L

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A

Sites not aligning to the query:

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

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, 44% coverage: 5:239/534 of query aligns to 11:240/346 of P9WMK5

query
sites
P9WMK5

D

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D16 (= D10) binding
H198 (= H197) binding
H200 (= H199) binding

Sites not aligning to the query:

322 G→F: Abolishes substrate channeling to HsaG.

4jn6C Crystal structure of the aldolase-dehydrogenase complex from mycobacterium tuberculosis hrv37 (see paper)
25% identity, 44% coverage: 5:239/534 of query aligns to 8:237/339 of 4jn6C

query
sites
4jn6C

D

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active site: D13 (= D10), H16 (≠ Y13), H195 (= H197), H197 (= H199)
binding manganese (ii) ion: D13 (= D10), H195 (= H197), H197 (= H199)
binding oxalate ion: R12 (= R9), M136 (= M140), V164 (≠ A168), S166 (= S170), H195 (= H197), H197 (= H199)

Sites not aligning to the query:

active site: 286
binding oxalate ion: 286

4lrsA Crystal and solution structures of the bifunctional enzyme (aldolase/aldehyde dehydrogenase) from thermomonospora curvata, reveal a cofactor-binding domain motion during NAD+ and coa accommodation whithin the shared cofactor-binding site
28% identity, 44% coverage: 5:240/534 of query aligns to 8:238/337 of 4lrsA

query
sites
4lrsA

D

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A

active site: D13 (= D10), H16 (≠ Y13), H195 (= H197), H197 (= H199)
binding magnesium ion: D13 (= D10), H195 (= H197), H197 (= H199)
binding pyruvic acid: R12 (= R9), D13 (= D10), F134 (= F137), M136 (= M140), V164 (≠ A168), S166 (= S170), H195 (= H197), H197 (= H199)

Sites not aligning to the query:

active site: 286
binding pyruvic acid: 286

3a9iA Crystal structure of homocitrate synthase from thermus thermophilus complexed with lys (see paper)
23% identity, 43% coverage: 2:232/534 of query aligns to 4:223/347 of 3a9iA

query
sites
3a9iA

K

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H

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N

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D

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N

N

T

A

L

Y

R

E

A

A

M

I

D

E

E

A

G

G

V

A

T

T

W

H

V

V

D

D

S

T

T

T

V

I

T

L

G

G

M

I

G

G

R

E

G

R

P

N

G

G

binding cobalt (ii) ion: E12 (≠ D10), H188 (= H197), H190 (= H199)
binding lysine: R11 (= R9), D91 (≠ Q94), S128 (≠ N138), T159 (≠ S170), H188 (= H197), H190 (= H199)

2zyfA Crystal structure of homocitrate synthase from thermus thermophilus complexed with magnesuim ion and alpha-ketoglutarate (see paper)
23% identity, 43% coverage: 2:232/534 of query aligns to 5:224/314 of 2zyfA

query
sites
2zyfA

K

K

H

I

L

I

D

D

C

S

T

T

L

L

R
|
R

D
x
E

G

G

G

E

Y
x
Q

Y

F

N

E

N

K

W

A

N

N

F

F

S

S

E

T

A

Q

L

D

I

K

A

V

Q

E

Y

I

I

A

T

K

A

A

M

L

Q

D

A

E

A

F

G

G

I

I

Q

E

T

Y

I

I

E

E

L

V

G

-

L

-

R

-

S

-

L

-

K

-

N

T

S

T

S

P

F

V

S

A

G

S

A

P

C

Q

A

S

Y

R

T

K

T

D

D

A

A

E

F

V

L

L

S

A

T

S

L

L

D

G

L

L

P

K

P

A

S

K

M

V

T

V

I

T

G
x
H

V

I

M

Q

V

C

N

R

-

L

G

D

S

A

E

A

L

K

V

V

G

A

K

V

N

E

A

T

G

G

Q

V

Q

Q

A

G

L

I

Q

D

L

L

L
|
L

F

F

P

G

S

T

P

S

A

K

S

G

E

R

S

-

P

-

V

-

D

D

L

I

V

P

R

R

I

I

A

-

C

-

H

-

V

-

H

-

E

-

F

I

A

E

E

E

A

A

L

K

P

E

A

V

A

I

S

A

W

Y

L

I

K

R

E

E

R

A

G

A

-

P

-

H

Y

V

D

E

V

V

G
x
R

F

F

N

S

L

A

M

E

Q

D

I

T

A

F

N

R

C

S

S

E

E

E

S

Q

E

D

I

L

K

L

A

A

L

V

A

Y

K

E

L

A

A

V

N

A

N

P

Y

Y

P

-

L

V

D

D

V

R

L

V

Y

G

F

L

A

A

D

D

S
x
T

M

V

G

G

S

V

M

A

S

T

P

P

D

R

D

Q

A

V

A

Y

Q

A

I

L

I

V

Q

R

W

E

L

V

R

R

S

R

E

V

W

V

Q

G

G

P

A

R

L

V

G

D

I

I

-

E

-

F

H
|
H

T

G

H
|
H

D

N

N

D

L

T

G

G

L

C

A

A

L

I

S

A

N

N

T

A

L

Y

R

E

A

A

M

I

D

E

E

A

G

G

V

A

T

T

W

H

V

V

D

D

S

T

T

T

V

I

T

L

G

G

M

I

G

G

R

E

G

R

P

N

G

G

active site: Q16 (≠ Y13)
binding 2-oxoglutaric acid: R12 (= R9), H72 (≠ G75), L94 (= L96), R127 (≠ G136), T160 (≠ S170), H189 (= H197)
binding magnesium ion: E13 (≠ D10), H189 (= H197), H191 (= H199)

P51016 4-hydroxy-2-oxovalerate aldolase; HOA; 4-hydroxy-2-keto-pentanoic acid aldolase; 4-hydroxy-2-oxopentanoate aldolase; EC 4.1.3.39 from Pseudomonas sp. (strain CF600) (see 2 papers)
25% identity, 41% coverage: 5:224/534 of query aligns to 13:227/345 of P51016

query
sites
P51016

D

D

C

V

T

T

L

L

R

R

D
|
D

G

G

G

S

Y

H

Y

A

N

I

N

R

W

H

N

Q

F

Y

S

T

E

L

A

D

L

D

I

V

A

R

Q

A

Y

I

I

A

T

R

A

A

M

L

Q

D

A

K

A

A

G

K

I

V

Q

D

T

S

I

I

E

E

L

V

G

A

L

H

-

G

R

D

S

G

L

L

K

Q

N

G

S

S

F

F

S

N

G

Y

A

G

C

F

A

G

Y

R

T

H

T

T

D

D

A

-

F

-

L

L

S

E

T

Y

L

I

D

E

L

-

P

-

S

-

M

-

T

-

I

-

G

-

V

-

M

-

V

-

N

-

G

-

S

-

E

A

L

V

V

A

G

G

K

E

N

I

A

S

G

H

Q

A

Q

Q

A

I

L

A

Q

T

L

L

F

L

P

P

S

G

P

I

A

G

S

S

-

V

-

H

-

D

-

L

-

K

-

N

-

A

-

Y

E

Q

S

A

P

G

V

A

D

R

L

V

V

V

R

R

I

V

A

A

C

T

H

H

V

C

H

T

E

E

F

A

A

D

E

V

A

S

L

K

P

Q

A

H

A

I

S

E

W

Y

L

A

K

R

E

N

R

L

G

G

Y

M

D

D

-

T

V

V

G

G

F

F

N

L

L

M

M

M

Q

S

I

H

A

M

N

I

C

P

S

A

E

E

S

-

E

K

I

L

K

A

A

E

L

Q

A

G

K

K

L

L

A

M

N

E

N

S

Y

Y

P

G

L

A

D

T

V

C

L

I

Y

Y

F

M

A

A

D

D

S

S

M

G

G

G

S

A

M

M

S

S

P

M

D

N

D

D

A

I

A

R

Q

D

I

R

I

M

Q

R

W

A

L

F

R

K

S

A

-

V

-

L

E

K

W

P

Q

E

G

T

A

Q

L

V

G

G

I

M

H
|
H

T

A

H
|
H

D

H

N

N

L

L

G

S

L

L

A

G

L

V

S

A

N

N

T

S

L

I

R

V

A

A

M

V

D

E

E

E

G

G

V

C

T

D

W

R

V

V

D

D

S

A

T

S

V

L

D18 (= D10) binding
H200 (= H197) binding
H202 (= H199) binding

Sites not aligning to the query:

1 modified: Initiator methionine, Removed

1nvmA Crystal structure of a bifunctional aldolase-dehydrogenase : sequestering a reactive and volatile intermediate (see paper)
25% identity, 41% coverage: 5:224/534 of query aligns to 12:226/340 of 1nvmA

query
sites
1nvmA

D

D

C

V

T

T

L

L

R
|
R

D
|
D

G

G

G

S

Y
x
H

Y

A

N

I

N

R

W

H

N

Q

F

Y

S

T

E

L

A

D

L

D

I

V

A

R

Q

A

Y

I

I

A

T

R

A

A

M

L

Q

D

A

K

A

A

G

K

I

V

Q

D

T

S

I

I

E

E

L

V

G

A

L

H

-

G

R

D

S

G

L

L

K

Q

N

G

S

S

F

F

S

N

G

Y

A

G

C

F

A

G

Y

R

T

H

T

T

D

D

A

-

F

-

L

L

S

E

T

Y

L

I

D

E

L

-

P

-

S

-

M

-

T

-

I

-

G

-

V

-

M

-

V

-

N

-

G

-

S

-

E

A

L

V

V

A

G

G

K

E

N

I

A

S

G

H

Q

A

Q

Q

A

I

L

A

Q

T

L

L

F

L

P

P

S

G

P

I

A

G

S

S

-

V

-

H

-

D

-

L

-

K

-

N

-

A

-

Y

E

Q

S

A

P

G

V

A

D

R

L

V

V

V

R

R

I

V

A

A

C

T

H

H

V

C

H

T

E

E

F

A

A

D

E

V

A

S

L

K

P

Q

A

H

A

I

S

E

W

Y

L

A

K

R

E

N

R

L

G

G

Y

M

D

D

-

T

V

V

G

G

F
|
F

N

L

L
x
M

M

M

Q

S

I

H

A

M

N

I

C

P

S

A

E

E

S

-

E

K

I

L

K

A

A

E

L

Q

A

G

K

K

L

L

A

M

N

E

N

S

Y

Y

P

G

L

A

D

T

V

C

L

I

Y

Y

F

M

A

A

D

D

S
|
S

M

G

G

G

S

A

M

M

S

S

P

M

D

N

D

D

A

I

A

R

Q

D

I

R

I

M

Q

R

W

A

L

F

R

K

S

A

-

V

-

L

E

K

W

P

Q

E

G

T

A

Q

L

V

G

G

I

M

H
|
H

T

A

H
|
H

D

H

N

N

L

L

G

S

L

L

A

G

L

V

S

A

N

N

T

S

L

I

R

V

A

A

M

V

D

E

E

E

G

G

V

C

T

D

W

R

V

V

D

D

S

A

T

S

V

L

active site: D17 (= D10), H20 (≠ Y13), H199 (= H197), H201 (= H199)
binding manganese (ii) ion: D17 (= D10), H199 (= H197), H201 (= H199)
binding oxalate ion: R16 (= R9), F138 (= F137), M140 (≠ L139), S170 (= S170), H199 (= H197), H201 (= H199)

Sites not aligning to the query:

active site: 290
binding oxalate ion: 290

2ztjA Crystal structure of homocitrate synthase from thermus thermophilus complexed with alpha-ketoglutarate (see paper)
23% identity, 43% coverage: 2:232/534 of query aligns to 5:222/312 of 2ztjA

query
sites
2ztjA

K

K

H

I

L

I

D

D

C

S

T

T

L

L

R
|
R

D
x
E

G

G

G

E

Y
x
Q

Y

F

N

E

N

K

W

A

N

N

F

F

S

S

E

T

A

Q

L

D

I

K

A

V

Q

E

Y

I

I

A

T

K

A

A

M

L

Q

D

A

E

A

F

G

G

I

I

Q

E

T

Y

I

I

E

E

L

V

G

-

L

-

R

-

S

-

L

-

K

-

N

T

S

T

S

P

F

V

S

A

G

S

A

P

C

Q

A

S

Y

R

T

K

T

D

D

A

A

E

F

V

L

L

S

A

T

S

L

L

D

G

L

L

P

K

P

A

S

K

M

V

T

V

I

T

G
x
H

V

I

M

Q

V

C

N

R

-

L

G

D

S

A

E

A

L

K

V

V

G

A

K

V

N

E

A

T

G

G

Q

V

Q

Q

A

G

L

I

Q

D

L

L

L
|
L

F

F

P

G

S

T

P

G

A

R

S

-

E

-

S

-

P

-

V

-

D

D

L

I

V

P

R

R

I

I

A

-

C

-

H

-

V

-

H

-

E

-

F

I

A

E

E

E

A

A

L

K

P

E

A

V

A

I

S

A

W

Y

L

I

K

R

E

E

R

A

G

A

-

P

-

H

Y

V

D

E

V

V

G
x
R

F

F

N

S

L

A

M

E

Q

D

I

T

A

F

N

R

C

S

S

E

E

E

S

Q

E

D

I

L

K

L

A

A

L

V

A

Y

K

E

L

A

A

V

N

A

N

P

Y

Y

P

-

L

V

D

D

V

R

L

V

Y

G

F

L

A
|
A

D

D

S
x
T

M

V

G

G

S

V

M

A

S

T

P

P

D

R

D

Q

A

V

A

Y

Q

A

I

L

I

V

Q

R

W

E

L

V

R

R

S

R

E

V

W

V

Q

G

G

P

A

R

L

V

G

D

I

I

-

E

-

F

H
|
H

T

G

H
|
H

D

N

N

D

L

T

G

G

L

C

A

A

L

I

S

A

N

N

T

A

L

Y

R

E

A

A

M

I

D

E

E

A

G

G

V

A

T

T

W

H

V

V

D

D

S

T

T

T

V

I

T

L

G

G

M

I

G

G

R

E

G

R

P

N

G

G

active site: Q16 (≠ Y13)
binding 2-oxoglutaric acid: R12 (= R9), H72 (≠ G75), L94 (= L96), R125 (≠ G136), A156 (= A168), T158 (≠ S170), H187 (= H197), H189 (= H199)
binding copper (ii) ion: E13 (≠ D10), H187 (= H197), H189 (= H199)

P51015 4-hydroxy-2-oxovalerate aldolase 4; HOA 4; 4-hydroxy-2-keto-pentanoic acid aldolase 4; 4-hydroxy-2-oxohexanoate aldolase; 4-hydroxy-2-oxopentanoate aldolase 4; EC 4.1.3.39; EC 4.1.3.43 from Paraburkholderia xenovorans (strain LB400) (see 3 papers)
27% identity, 41% coverage: 5:221/534 of query aligns to 12:223/346 of P51015

query
sites
P51015

D

D

C

M

T

T

L

L

R
|
R

D

D

G

G

G

M

Y
x
H

Y

P

N

K

N

R

W

H

N

Q

F

M

S

T

E

L

A

E

L

Q

I

M

A

K

Q

S

Y

I

I

A

T

C

A

G

M

L

Q

D

A

A

G

G

I

I

Q

P

T

L

I

I

E

E

L

V

G

T

L

H

-

G

R

D

S

G

L

L

K

G

N

G

S

S

F

V

S

N

-

Y

G

G

A

F

C

P

A

A

Y

H

T

S

T

D

D

E

A

E

F

Y

L

L

S

G

T

A

L

V

D

-

L

-

P

I

P

P

S

L

M

M

T

-

I

-

G

-

V

-

M

-

V

-

N

-

G

-

S

-

E

-

L

-

V

-

G

-

K

K

N

Q

A

A

G

K

Q

V

Q

S

A

A

L
|
L

Q

-

L

-

L

L

F
x
L

P

P

-

G

-

I

-

G

-

T

-

V

-

E

-

H

-

L

S

K

P

M

A

A

S

K

E

D

S

L

P

G

V

V

D

N

L

T

V

I

R

R

I

V

A

A

C

T

H

H

V

C

H

T

E

E

F

A

A

D

E

V

A

S

L

E

P

Q

A

H

A

I

S

T

W

Q

L

S

K

R

E

K

R

L

G

G

Y

L

D

D

-

T

V

V

G

G

F

F

N

-

L

L

M

M

Q

M

I

A

A

H

N

M

C

A

S

S

E

P

S

E

E

K

I

L

K

V

A

S

L

Q

A

A

K

L

L

L

A

M

N

Q

N

G

Y

Y

P

G

L

A

D

N

V

C

L

I

Y

Y

F

V

A

T

D

D

S

S

M

A

G

G

S

Y

M

M

S

L

P

P

D

D

A

V

A

K

Q

A

I

R

I

L

Q

S

W

A

L

V

R

R

S

A

E

A

W

L

-

K

-

P

Q

E

G

T

A

E

L

L

G

G

I

F

H

H

T

G

H

H

D

H

N

N

L

L

G

A

L

M

A

G

L

V

S

A

N

N

T

S

L

I

R

A

A

A

M

I

D

E

E

A

G

G

V

A

T

T

W

R

V

I

D

D

R16 (= R9) mutation to A: Loss of aldol cleavage activity.; mutation to K: 4000-fold decrease in the catalytic efficiency of the aldol cleavage reaction.
H20 (≠ Y13) mutation H->A,S: 100-fold decrease in the catalytic efficiency of the aldol cleavage reaction. Dramatic reduction in acetaldehyde and propanaldehyde channeling efficiency by more than 70%.
L87 (= L93) mutation to A: 32-fold reduction in the catalytic efficiency with acetaldehyde as substrate of the aldol addition reaction, but no change in the catalytic efficiency using propanaldehyde; thus, exhibits a 40-fold preference for propanaldehyde over acetaldehyde.; mutation L->N,W: Loss of aldolase activity (with either enantiomer of HOPA), but retains some decarboxylase activity for the smaller oxaloacetate substrate. In the retro-aldol cleavage reaction, is inactive toward 4(S)-HOPA but is active toward 4(R)-HOPA, albeit with a great reduction in catalytic efficiency, and in the aldol addition reaction, produces also exclusively the 4(R)-enantiomer; when associated with F-290.
L89 (≠ F97) mutation to A: As the wild-type enzyme, exhibits similar catalytic efficiency with acetaldehyde or propanaldehyde as substrate in the aldol addition reaction but displays higher catalytic efficiency with longer aldehydes (50-fold increase using pentaldehyde). Shows a reduction in aldehyde channeling efficiency by 30%.

Sites not aligning to the query:

290 Y→F: Loss of stereochemical control as the mutant is able to catalyze the aldol cleavage of substrates with both R and S configurations at C4 with similar kinetic parameters. 3.5-fold decrease in the catalytic efficiency of the aldol cleavage reaction. Reduction in aldehyde channeling efficiency by more than 30%. In the retro-aldol cleavage reaction, is inactive toward 4(S)-HOPA but is active toward 4(R)-HOPA, albeit with a great reduction in catalytic efficiency, and in the aldol addition reaction, produces also exclusively the 4(R)-enantiomer; when associated with N-87 or W-87.; Y→S: Loss of stereochemical control as the mutant is able to catalyze the aldol cleavage of substrates with both R and S configurations at C4 with similar kinetic parameters. 3.5-fold decrease in the catalytic efficiency of the aldol cleavage reaction.
322 G→A: Displays a reduction in aldehyde channeling efficiency of about 20%.; mutation G->F,L: Unable to channel either acetaldehyde or propanaldehyde.
323 G→A: Able to channel butyraldehyde (with less efficiency than wild-type) but not its isomer isobutyraldehyde.; G→F: Unable to channel either acetaldehyde or propanaldehyde.; G→L: Able to channel acetaldehyde but not the larger propanaldehyde.

O87198 Homocitrate synthase; HCS; EC 2.3.3.14 from Thermus thermophilus (strain ATCC BAA-163 / DSM 7039 / HB27) (see paper)
23% identity, 43% coverage: 2:232/534 of query aligns to 5:230/376 of O87198

query
sites
O87198

K

K

H

I

L

I

D

D

C

S

T

T

L

L

R
|
R

D
x
E

G

G

G

E

Y

Q

Y

F

N

E

N

K

W

A

N

N

F

F

S

S

E

T

A

Q

L

D

I

K

A

V

Q

E

Y

I

I

A

T

K

A

A

M

L

Q

D

A

E

A

F

G

G

I

I

Q

E

T

Y

I

I

E

E

L

V

G

-

L

-

R

-

S

-

L

-

K

-

N

T

S

T

S

P

F

V

S

A

G

S

A

P

C

Q

A

S

Y

R

T

K

T

D

D

A

A

E

F

V

L

L

S

A

T

S

L

L

D

G

L

L

P

K

P

A

S

K

M

V

T

V

I

T

G
x
H

V

I

M

Q

V

C

N

R

-

L

G

D

S

A

E

A

L

K

V

V

G

A

K

V

N

E

A

T

G

G

Q

V

Q

Q

A

G

L

I

Q
x
D

L

L

F

F

P

G

S

T

P

S

A

K

-

Y

-

L

-

R

S

A

E

A

S

H

P

G

V

R

D

D

L

I

V

P

R

R

I

I

A

-

C

-

H

-

V

-

H

-

E

-

F

I

A

E

E

E

A

A

L

K

P

E

A

V

A

I

S

A

W

Y

L

I

K

R

E

E

R

A

G

A

-

P

-

H

Y

V

D

E

V

V

G
x
R

F

F

N
x
S

L

A

M

E

Q

D

I

T

A

F

N

R

C

S

S

E

E

E

S

Q

E

D

I

L

K

L

A

A

L

V

A

Y

K

E

L

A

A

V

N

A

N

P

Y

Y

P

-

L

V

D

D

V

R

L

V

Y

G

F

L

A

A

D

D

S
x
T

M

V

G

G

S

V

M

A

S

T

P

P

D

R

D

Q

A

V

A

Y

Q

A

I

L

I

V

Q

R

W

E

L

V

R

R

S

R

E

V

W

V

Q

G

G

P

A

R

L

V

G

D

I

I

-

E

-

F

H
|
H

T

G

H
|
H

D

N

N

D

L

T

G

G

L

C

A

A

L

I

S

A

N

N

T

A

L

Y

R

E

A

A

M

I

D

E

E

A

G

G

V

A

T

T

W

H

V

V

D

D

S

T

T

T

V

I

T

L

G

G

M

I

G

G

R

E

G

R

P

N

G

G

R12 (= R9) binding
E13 (≠ D10) binding
H72 (≠ G75) 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 (≠ Q94) binding
R133 (≠ G136) binding
S135 (≠ N138) binding
T166 (≠ S170) binding ; binding
H195 (= H197) binding
H197 (= H199) binding

Q8F3Q1 (R)-citramalate synthase CimA; LiCMS; EC 2.3.3.21 from Leptospira interrogans serogroup Icterohaemorrhagiae serovar Lai (strain 56601) (see 2 papers)
23% identity, 47% coverage: 4:253/534 of query aligns to 11:263/516 of Q8F3Q1

query
sites
Q8F3Q1

L

L

D

D

C

V

T

T

L

L

R
|
R

D
|
D

G

G

G

E

Y

Q

Y

T

N

R

N

G

W

V

N

S

F

F

S

S

-

T

-

S

E

E

A

K

L

L

-

N

I

I

A

A

Q

K

Y

F

I

L

T

-

A

-

M

L

Q

Q

A

K

A

L

G

N

I

V

Q

D

T

R

I

V

E

E

L

I

G

A

L

-

R

-

S

S

L

A

K

R

N

V

S

S

S

K

F

G

S

E

G

L

A

E

C

T

A

V

Y

Q

T

K

T

I

D

M

A

E

F

W

L

A

S

A

T

T

L

E

D

Q

L

L

P

T

P

E

S

R

M

I

T

E

I

I

G
x
L

V

G

M
x
F

V

V

N

D

G

G

S

N

E

K

L

T

V

V

G

D

-

W

-

I

K

K

N

D

A

S

G

G

Q

A

Q

K

A

V

L

L

Q

N

L

L

L
|
L

-

T

-

K

-

G

-

S

-

L

-

H

F

L

P

E

S

K

P

Q

A

L

S

G

E

K

S

T

P

P

V

K

D

E

L

F

V

F

R

T

I

D

A

V

C

S

H

F

V

V

H

I

E

E

F

Y

A

A

-

I

-

K

E

S

A

G

L

L

P

K

A

I

A

N

S

V

W
x
Y

L

L

K
x
E

E

D

R

-

G

-

Y

W

D

S

V

N

G

G

F

F

N

R

L

-

M

-

Q

-

I

-

A

-

N

-

C

N

S

S

E

P

S

D

E

Y

I

V

K

K

A

S

L

L

A

V

K

E

L

H

A

L

N

S

N

K

Y

E

P

H

L

I

D

E

V

R

L

I

Y

F

F

L

A

P

D

D

S
x
T

M

L

G

G

S

V

M

L

S

S

P

P

D

E

A

T

A

F

Q

Q

I

G

I

V

Q

D

W

S

L

L

R

I

S

Q

E

K

W

Y

Q

P

G

D

A

I

-

H

L

F

G

E

I

F

H

H

T

G

H

H

D

N

N

D

L

Y

G

D

L

L

A

S

L

V

S

A

N

N

T

S

L

L

R

Q

A

A

M

I

D

R

E

A

G

G

V

V

T

K

W

G

V

L

D

H

S

A

T

S

V

I

T

N

G

G

M

L

G

G

R

E

G

R

P

A

G

G

N

N

A

T

R

P

T

L

E

E

E

A

L

L

A

V

I

T

E

T

I

I

A

H

A

D

R

K

T

S

R

N

K

S

P

K

A

T

N

N

L

I

R16 (= R9) mutation R->K,Q: Loss of activity.
RD 16:17 (= RD 9:10) binding
D17 (= D10) 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 (≠ G75) 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 (≠ M77) mutation to A: 5-fold increase in Km for acetyl-CoA and 120-fold decrease in kcat.
L104 (= L96) mutation to V: 1.8-fold increase in Km for pyruvate and 3.4-fold decrease in kcat.
Y144 (≠ W127) 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 (≠ K129) mutation E->D,Q: Minor effects on the binding of acetyl-CoA, but causes a strong decrease in kcat.
T179 (≠ S170) 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.

3bliA Crystal structure of the catalytic domain of licms in complexed with pyruvate and acetyl-coa (see paper)
23% identity, 47% coverage: 4:253/534 of query aligns to 5:257/311 of 3bliA

query
sites
3bliA

L

L

D

D

C

V

T

T

L

L

R
|
R

D
|
D

G

G

G

E

Y
x
Q

Y

T

N

R

N

G

W

V

N

S

F

F

S

S

-

T

-

S

E

E

A

K

L

L

-

N

I

I

A

A

Q

K

Y

F

I

L

T

-

A

-

M

L

Q

Q

A

K

A

L

G

N

I

V

Q

D

T

R

I

V

E

E

L

I

G

A

L

-

R

-

S

S

L

A

K
x
R

N
x
V

S

S

S

K

F

G

S

E

G

L

A

E

C

T

A

V

Y

Q

T

K

T

I

D

M

A

E

F

W

L

A

S

A

T

T

L

E

D

Q

L

L

P

T

P

E

S

R

M

I

T

E

I

I

G

L

V

G

M

F

V

V

N

D

G

G

S

N

E

K

L

T

V

V

G

D

-

W

-

I

K

K

N

D

A

S

G

G

Q

A

Q

K

A

V

L

L

Q

N

L

L

-

T

-

K

-

G

-

S

-

L

-

H

F

L

P

E

S

K

P

Q

A

L

S

G

E

K

S

T

P

P

V

K

D

E

L

F

V

F

R

T

I

D

A

V

C

S

H

F

V

V

H

I

E

E

F

Y

A

A

-

I

-

K

E

S

A

G

L

L

P

K

A

I

A

N

S

V

W
x
Y

L

L

K
x
E

E

D

R

-

G

-

Y

W

D

S

V

N

G

G

F

F

N

R

L

-

M

-

Q

-

I

-

A

-

N

-

C

N

S

S

E

P

S

D

E

Y

I

V

K

K

A

S

L

L

A

V

K

E

L

H

A

L

N

S

N

K

Y

E

P

H

L

I

D

E

V

R

L

I

Y

F

F

L

A
x
P

D

D

S
x
T

M

L

G

G

S

V

M

L

S

S

P

P

D

E

A

T

A

F

Q

Q

I

G

I

V

Q

D

W

S

L

L

R

I

S

Q

E

K

W

Y

Q

P

G

D

A

I

-

H

L

F

G

E

I

F

H
|
H

T

G

H
|
H

D

N

N

D

L

Y

G

D

L

L

A

S

L

V

S

A

N

N

T

S

L

L

R

Q

A

A

M

I

D

R

E

A

G

G

V

V

T

K

W

G

V

L

D

H

S

A

T

S

V

I

T

N

G

G

M

L

G

G

R

E

G

R

P

A

G

G

N

N

A

T

R

P

T

L

E

E

E

A

L

L

A

V

I

T

E

T

I

I

A

H

A

D

R

K

T

S

R

N

K

S

P

K

A

T

N

N

L

I

active site: Q14 (≠ Y13)
binding acetyl coenzyme *a: Q14 (≠ Y13), R47 (≠ K47), V48 (≠ N48), E140 (≠ K129)
binding pyruvic acid: R10 (= R9), Y138 (≠ W127), P171 (≠ A168), T173 (≠ S170)
binding zinc ion: D11 (= D10), H201 (= H197), H203 (= H199)

Q9FG67 Methylthioalkylmalate synthase 1, chloroplastic; 2-isopropylmalate synthase 3; EC 2.3.3.17 from Arabidopsis thaliana (Mouse-ear cress) (see paper)
27% identity, 21% coverage: 135:246/534 of query aligns to 221:341/506 of Q9FG67

query
sites
Q9FG67

V

L

G

G

F

F

N

N

L

D

M

I

Q

Q

I

F

A

G

N

-

C

C

S

E

E

D

-

G

-

R

S

S

E

D

I

K

K

D

A

F

L

L

A

C

K

K

L

I

-

L

-

G

-

E

A

A

N

I

N

K

Y

A

P

G

L

V

D

T

V

V

L

V

Y

T

F

I

A

G

D

D

S

T

M

V

G

G

S

I

M

N

S

M

P

P

D

H

D

E

A

Y

A

G

Q

E

I

L

I

V

Q

T

W

Y

L

L

R

K

S

A

E

N

W

T

Q

P

G

G

-

I

-

D

-

V

A

V

L

V

G
x
A

I

V

H

H

T

C

H

H

D

N

N

D

L

L

G

G

L

L

A

A

L

T

S

A

N

N

T

S

L

I

R

A

A

G

M

I

D

R

E

A

G

G

V

A

T

R

W

Q

V

V

D

E

S

V

T

T

V

I

T

N

G

G

M

I

G

G

R

E

G

R

P

S

G

G

N

N

A

A

R

S

T

L

E

E

L

V

A

V

I

M

E

A

I

L

A

K

A

C

R

R

A290 (≠ G195) mutation to T: In gsm1-2; loss of conversion of C3 to C4 glucosinolates.

Sites not aligning to the query:

102 S→F: In gsm1-1; loss of conversion of C3 to C4 glucosinolates.

Q9FN52 Methylthioalkylmalate synthase 3, chloroplastic; 2-isopropylmalate synthase 2; Methylthioalkylmalate synthase-like; EC 2.3.3.17 from Arabidopsis thaliana (Mouse-ear cress) (see paper)
31% identity, 15% coverage: 167:246/534 of query aligns to 258:341/503 of Q9FN52

query
sites
Q9FN52

F

F

A

A

D

D

S

T

M

V

G
|
G

S

I

M

N

S

M

P

P

D

Q

D

E

A

F

A

G

Q

E

I

L

I

V

Q

A

W

Y

L

V

R

I

S

E

E

N

W

T

Q

P

G

G

A

A

-

D

-

I

-

V

L

F

G

A

I

I

H

H

T

C

H

H

D

N

N

D

L

L

G

G

L

V

A

A

L

T

S

A

N

N

T

T

L

I

R

S

A

G

M

I

D

C

E

A

G

G

V

A

T

R

W

Q

V

V

D

E

S

V

T

T

V

I

T

N

G

G

M

I

G

G

R

E

G

R

P

S

G

G

N

N

A

A

R

P

T

L

E

E

L

V

A

V

I

M

E

A

I

L

A

K

A

C

R

R

G263 (= G172) mutation to E: In gsm2-1; loss of activity and lack of C6, C7 and C8 aliphatic glucosinolates.

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)
35% identity, 14% coverage: 165:239/534 of query aligns to 245:326/370 of Q8TB92

query
sites
Q8TB92

L

I

Y

S

F

L

A

G

D

D

S

T

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G

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G

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E

E

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-

P

G

G

A

A

L

L

G

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H
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H

T

C

H

H

D

D

N

T

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Y

G

G

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A

A

L

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A

N

N

T

I

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L

R

T

A

A

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D

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E

M

G

G

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N

W

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D

S

S

T

A

V

V

T

S

G

G

M

L

G

G

R

G

G

C

P

P

-

Y

-

A

-

K

-

G

-

A

-

S

G

G

N

N

A

V

R

A

T

T

E

E

E

D

L

L

H278 (= H197) mutation to R: Abolishes catalytic activity.

Sites not aligning to the query:

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

3mp5B Crystal structure of human lyase r41m in complex with hmg-coa (see paper)
37% identity, 14% coverage: 165:239/534 of query aligns to 173:254/296 of 3mp5B

query
sites
3mp5B

L

I

Y

S

F

L

A

G

D

D

S
x
T

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A

A

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H

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H

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D

N

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G

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A

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N

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G

G
x
C

P

P

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-

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-

G

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A

-

S

G

G

N

N

A

L

R

A

T

T

E

E

E

D

L

L

binding 3-hydroxy-3-methylglutaryl-coenzyme a: T178 (≠ S170), C239 (≠ G230)
binding magnesium ion: H206 (= H197), H208 (= H199)

Sites not aligning to the query:

binding 3-hydroxy-3-methylglutaryl-coenzyme a: 15, 18, 51, 54, 100, 111, 113, 140, 142
binding magnesium ion: 15

3mp3B Crystal structure of human lyase in complex with inhibitor hg-coa (see paper)
37% identity, 14% coverage: 165:239/534 of query aligns to 173:254/296 of 3mp3B

query
sites
3mp3B

L

I

Y

S

F

L

A

G

D

D

S
x
T

M

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G

G

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M

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A

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H

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D

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A

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N

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G

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G

G

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P

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G

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A

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S

G

G

N

N

A

L

R

A

T

T

E

E

E

D

L

L

Sites not aligning to the query:

2cw6A Crystal structure of human hmg-coa lyase: insights into catalysis and the molecular basis for hydroxymethylglutaric aciduria (see paper)
37% identity, 14% coverage: 165:239/534 of query aligns to 173:254/296 of 2cw6A

query
sites
2cw6A

L

I

Y

S

F

L

A

G

D

D

S

T

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G

G

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A

A

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H
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H

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D

N

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G

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A

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N

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G

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G

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P

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G

G

N
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N

A

L

R

A

T

T

E

E

E

D

L

L

binding magnesium ion: H206 (= H197), H208 (= H199), N248 (= N233)

Sites not aligning to the query:

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)
37% identity, 14% coverage: 165:239/534 of query aligns to 200:281/325 of P35914

query
sites
P35914

L
x
I

Y

S

F

L

A
x
G

D
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D

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G

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A

A

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H

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D

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G

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A

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G

G

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N

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T

E
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E

E
x
D

L

L

I200 (≠ L165) to F: in HMGCLD; activity lower than 5% respect to the wild-type
G203 (≠ A168) to E: in HMGCLD; complete loss of activity; dbSNP:rs1553131940
D204 (= D169) mutation to A: Reduced activity, and reduced affinity for metal cofactor and substrate.
H233 (= H197) to R: in HMGCLD; loss of activity; dbSNP:rs727503963; mutation to A: Loss of activity, and reduced proton exchange rate.
E279 (= E237) mutation to A: Reduced thermal stability, but normal activity.
D280 (≠ E238) mutation to A: Normal activity.

Sites not aligning to the query:

37 E → K: in HMGCLD; activity lower than 5% respect to the wild-type; E→D: Normal activity.
41 R → Q: in HMGCLD; loss of activity and of proton exchange; dbSNP:rs121964997; R→M: Reduced activity, and loss of proton exchange.
42 D → E: in HMGCLD; reduced activity; D → G: in HMGCLD; loss of activity; dbSNP:rs1467902610; D → H: in HMGCLD; loss of activity; mutation D->A,N: Loss of activity, and reduced proton exchange rate.
48 K → N: in HMGCLD; abolishes almost all enzymatic activity
72 E→A: Loss of activity, and reduced affinity for metal cofactor and substrate.
142 S → F: in HMGCLD; activity lower than 5% respect to the wild-type
174 C → Y: in HMGCLD; activity lower than 5% respect to the wild-type; dbSNP:rs765475941
192 F → S: in HMGCLD; activity lower than 5% respect to the wild-type
323 modified: Interchain; C→S: Abolishes interchain homodimerization. Exhibits no DTT stimulated activity.

Query Sequence

>PP_1791 FitnessBrowser__Putida:PP_1791
MKHLDCTLRDGGYYNNWNFSEALIAQYITAMQAAGIQTIELGLRSLKNSSFSGACAYTTD
AFLSTLDLPPSMTIGVMVNGSELVGKNAGQQALQLLFPSPASESPVDLVRIACHVHEFAE
ALPAASWLKERGYDVGFNLMQIANCSESEIKALAKLANNYPLDVLYFADSMGSMSPDDAA
QIIQWLRSEWQGALGIHTHDNLGLALSNTLRAMDEGVTWVDSTVTGMGRGPGNARTEELA
IEIAARTRKPANLIPLMTLLREHFKPMQVKYGWGTNPYYYLAGKYGIHPTYIQEMLGDSR
FGEEDILAVIEYLRNEGGKKFSVHTLDAARHFYRGAPTGQWAPQDLLAGQDVLLLGTGPG
VAAHRQALEHFIRQHKPVVMALNTQSSIAAELIDVRVACHPVRLLADCEAHIELPQPLIT
PYSMLPMDVQGALANKNVLDFGLNVQPDKFTFEDTHCTIPTSLVVAYAMAAASSGKAKRI
LMAGFDGYPGEDPRNADTNKLFRQYQDTQSSTPLLCLTPTRYDISCQSVYGPLK

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