SitesBLAST

SitesBLAST – Find functional sites

SitesBLAST

Comparing WP_079555959.1 NCBI__GCF_002201795.1:WP_079555959.1 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)

P14550 Aldo-keto reductase family 1 member A1; Alcohol dehydrogenase [NADP(+)]; Aldehyde reductase; Glucuronate reductase; Glucuronolactone reductase; S-nitroso-CoA reductase; ScorR; EC 1.1.1.2; EC 1.1.1.372; EC 1.1.1.54; EC 1.1.1.19; EC 1.1.1.20; EC 1.6.-.- from Homo sapiens (Human) (see 5 papers)
41% identity, 88% coverage: 17:314/339 of query aligns to 6:299/325 of P14550

query
sites
P14550

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Y50 (= Y64) active site, Proton donor; mutation to A: Abolished reductase activity.; mutation to F: Complete loss of enzymatic activity.; mutation to H: Complete loss of enzymatic activity.
N52 (= N66) to S: reduced activity towards daunorubicin; dbSNP:rs2229540
E55 (= E69) to D: reduced activity towards daunorubicin; dbSNP:rs6690497
K80 (= K93) Lowers pKa of active site Tyr; mutation to M: Complete loss of enzymatic activity.
H113 (= H124) mutation to Q: Strong decrease in enzymatic activity.
K127 (≠ R140) mutation to A: Abolished S-nitroso-CoA reductase activity without affecting ability to reduce S-nitrosoglutathione, glyceraldehyde or glucuronate.
I299 (= I314) mutation to A: No change in enzymatic activity.; mutation to C: No change in enzymatic activity.

Sites not aligning to the query:

1 modified: Initiator methionine, Removed
300 V→C: No change in enzymatic activity.
312 R→A: Abolished S-nitrosoglutathione reductase activity without affecting ability to reduce S-nitroso-CoA.

3cv7A Crystal structure of porcine aldehyde reductase ternary complex (see paper)
40% identity, 88% coverage: 17:314/339 of query aligns to 6:299/322 of 3cv7A

query
sites
3cv7A

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active site: D45 (= D59), Y50 (= Y64), K80 (= K93), H113 (= H124)
binding 3,5-dichloro-2-hydroxybenzoic acid: W22 (≠ F33), Y50 (= Y64), W82 (= W95), H113 (= H124)
binding nadp nicotinamide-adenine-dinucleotide phosphate: G20 (= G31), T21 (= T32), W22 (≠ F33), Y50 (= Y64), H113 (= H124), Q184 (≠ E196), Y210 (= Y222), S211 (= S223), P212 (= P224), L213 (≠ I225), S215 (= S227), A246 (= A260), I261 (= I275), P262 (= P276), K263 (≠ F277), S264 (= S278), V265 (= V279), T266 (≠ S280), R269 (≠ K283), Q272 (≠ N286), N273 (= N287)

Sites not aligning to the query:

binding 3,5-dichloro-2-hydroxybenzoic acid: 309

3fx4A Porcine aldehyde reductase in ternary complex with inhibitor (see paper)
40% identity, 88% coverage: 17:314/339 of query aligns to 6:299/325 of 3fx4A

query
sites
3fx4A

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active site: D45 (= D59), Y50 (= Y64), K80 (= K93), H113 (= H124)
binding [(5Z)-5-{[3-(carboxymethoxy)-4-methoxyphenyl]methylidene}-2,4-dioxo-1,3-thiazolidin-3-yl]acetic acid: W22 (≠ F33), Y50 (= Y64), H113 (= H124), R218 (= R230), A219 (≠ P231), F298 (≠ L313), I299 (= I314)
binding nadp nicotinamide-adenine-dinucleotide phosphate: G20 (= G31), T21 (= T32), W22 (≠ F33), D45 (= D59), Y50 (= Y64), H113 (= H124), Q184 (≠ E196), Y210 (= Y222), S211 (= S223), P212 (= P224), L213 (≠ I225), S215 (= S227), A246 (= A260), I261 (= I275), P262 (= P276), K263 (≠ F277), S264 (= S278), V265 (= V279), T266 (≠ S280), R269 (≠ K283), Q272 (≠ N286), N273 (= N287)

Sites not aligning to the query:

binding [(5Z)-5-{[3-(carboxymethoxy)-4-methoxyphenyl]methylidene}-2,4-dioxo-1,3-thiazolidin-3-yl]acetic acid: 300

P50578 Aldo-keto reductase family 1 member A1; Alcohol dehydrogenase [NADP(+)]; Aldehyde reductase; Glucuronate reductase; Glucuronolactone reductase; S-nitroso-CoA reductase; ScorR; EC 1.1.1.2; EC 1.1.1.372; EC 1.1.1.54; EC 1.1.1.19; EC 1.1.1.20; EC 1.6.-.- from Sus scrofa (Pig) (see 2 papers)
40% identity, 88% coverage: 17:314/339 of query aligns to 6:299/325 of P50578

query
sites
P50578

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V

K

R

P

P

V

A

V

V

N

L

E

Q

M

V

E

E

L

C

H

H

P

P

H

Y

F

L

Q

A

Q

Q

S

N

E

E

L

L

F

I

N

A

Y

H

L

C

A

Q

E

A

R

R

N

G

I

L

Q

E

P

V

I

T

G

A

Y

Y

S
|
S

P

P

I
x
L

G

G

S
|
S

P
x
S

K

D

R

R

P

A

E

W

R

R

D

D

R

-

T

-

K

P

E

N

D

E

T

P

V

V

D

L

I

L

E

E

D

E

P

P

V

V

I

V

V

Q

K

A

V

L

A

A

E

E

R

K

L

Y

N

N

L

R

H

S

P

P

A

A

E

Q

V

I

C

L

I

L

K

R

W

W

G

Q

V

V

Q

Q

R

R

G

K

E

V

V

I

V

C

I

I

P

P

F
x
K

S
|
S

V
|
V

S
x
T

P

P

A

S

K
x
R

I

I

V

L

N
x
Q

N
|
N

L

I

K

Q

A

-

V

V

T

F

G

D

E

F

S

T

I

F

T

S

N

P

E

E

M

M

K

K

Q

Q

I

L

A

D

G

A

I

L

D

N

K

K

N

N

C

L

R

R

L

F

I

I

T21 (= T32) binding NADP(+)
W22 (≠ F33) binding NADP(+)
D45 (= D59) binding NADP(+)
Y50 (= Y64) active site, Proton donor; mutation to F: Abolished aldo-keto reductase activity.
S162 (= S174) binding NADP(+)
N163 (= N175) binding NADP(+)
S211 (= S223) binding NADP(+)
L213 (≠ I225) binding NADP(+)
S215 (= S227) binding NADP(+)
S216 (≠ P228) binding NADP(+)
K263 (≠ F277) binding NADP(+)
S264 (= S278) binding NADP(+)
V265 (= V279) binding NADP(+)
T266 (≠ S280) binding NADP(+)
R269 (≠ K283) binding NADP(+)
Q272 (≠ N286) binding NADP(+)
N273 (= N287) binding NADP(+)

3h4gA Structure of aldehyde reductase holoenzyme in complex with potent aldose reductase inhibitor fidarestat: implications for inhibitor binding and selectivity (see paper)
40% identity, 88% coverage: 17:314/339 of query aligns to 6:299/320 of 3h4gA

query
sites
3h4gA

V

V

T

L

L

L

S

H

N

T

G

G

A

Q

K

K

I

M

P

P

V

L

L

I

G

G

L

L

G
|
G

T
|
T

F
x
W

G

K

S

S

D

E

N

-

Y

-

N

-

A

P

N

G

Q

Q

I

V

A

K

E

A

A

A

V

I

D

K

F

Y

A

A

I

L

R

T

K

V

G

G

Y

Y

R

R

H

H

I

I

D
|
D

C

C

A

A

S

A

V

I

Y
|
Y

M

G

N

N

E

E

P

L

E

E

I

I

G

G

N

E

A

A

I

L

S

Q

G

E

L

T

L

V

N

G

E

P

G

G

-

K

V

A

V

V

K

P

R

R

E

E

L

L

W

F

V

V

T

T

S

S

K
|
K

V

L

W

W

N

N

D

T

A

K

H

H

-

H

-

P

D

E

E

D

V

V

V

E

E

P

S

A

C

L

K

R

K

K

S

T

L

L

N

A

D

D

L

L

K

Q

L

L

D

E

Y

Y

L

L

D

D

L

L

Y

Y

L

L

V

M

H
|
H

W
|
W

P

P

F

Y

P

A

-

F

-

E

-

R

-

G

-

D

N

N

Y

P

H

F

A

P

P

K

G

N

C

A

D

D

G

G

D

T

A

I

R

R

N

-

P

-

D

-

S

-

R

-

P

-

Y

Y

N

D

H

A

E

T

K

H

Y

Y

M

K

E

D

T

T

W

W

R

K

Q

A

M

L

E

E

K

A

L

L

V

V

E

A

M

K

G

G

L

L

V

V

K

R

S

A

I

L

G

G

T

L

S
|
S

N
|
N

M

F

T

S

I

S

P

R

K

Q

M

I

E

D

L

D

L

V

L

L

R

S

D

V

A

A

K

S

I

V

K

R

P

P

V

A

V

V

N

L

E
x
Q

M

V

E

E

L

C

H

H

P

P

H

Y

F

L

Q

A

Q

Q

S

N

E

E

L

L

F

I

N

A

Y

H

L

C

A

Q

E

A

R

R

N

G

I

L

Q

E

P

V

I

T

G

A

Y
|
Y

S
|
S

P
|
P

I
x
L

G

G

S
|
S

P

S

K
x
D

R

R

P

A

E
x
W

R

R

D

D

R

-

T

-

K

P

E

N

D

E

T

P

V

V

D

L

I

L

E

E

D

E

P

P

V

V

I

V

V

Q

K

A

V

L

A

A

E

E

R

K

L

Y

N

N

L

R

H

S

P

P

A
|
A

E

Q

V

I

C

L

I

L

K

R

W

W

G

Q

V

V

Q

Q

R

R

G

K

E

V

V

I

V

C

I
|
I

P
|
P

F
x
K

S
|
S

V
|
V

S
x
T

P

P

A

S

K
x
R

I

I

V

L

N
x
Q

N
|
N

L

I

K

Q

A

-

V

V

T

F

G

D

E

F

S

T

I

F

T

S

N

P

E

E

M

M

K

K

Q

Q

I

L

A

D

G

A

I

L

D

N

K

K

N

N

C

L

R

R

L

F

I
|
I

active site: D45 (= D59), Y50 (= Y64), K80 (= K93), H113 (= H124)
binding (2s,4s)-2-aminoformyl-6-fluoro-spiro[chroman-4,4'-imidazolidine]-2',5'-dione: W22 (≠ F33), Y50 (= Y64), H113 (= H124), W114 (= W125), W220 (≠ E232), I299 (= I314)
binding nadp nicotinamide-adenine-dinucleotide phosphate: G20 (= G31), T21 (= T32), W22 (≠ F33), D45 (= D59), Y50 (= Y64), H113 (= H124), S162 (= S174), N163 (= N175), Q184 (≠ E196), Y210 (= Y222), S211 (= S223), P212 (= P224), L213 (≠ I225), S215 (= S227), D217 (≠ K229), A246 (= A260), I261 (= I275), P262 (= P276), K263 (≠ F277), S264 (= S278), V265 (= V279), T266 (≠ S280), R269 (≠ K283), Q272 (≠ N286), N273 (= N287)

Sites not aligning to the query:

binding (2s,4s)-2-aminoformyl-6-fluoro-spiro[chroman-4,4'-imidazolidine]-2',5'-dione: 300, 301

P16116 Aldo-keto reductase family 1 member B1; 20-alpha-hydroxysteroid dehydrogenase; 20-alpha-HSD; Aldehyde reductase; Aldose reductase; AR; EC 1.1.1.21; EC 1.1.1.300; EC 1.1.1.372; EC 1.1.1.54 from Bos taurus (Bovine) (see paper)
43% identity, 87% coverage: 17:312/339 of query aligns to 4:296/315 of P16116

query
sites
P16116

V

I

T

V

L

L

S

Y

N

T

G

G

A

A

K

K

I

M

P

P

V

I

L

L

G

G

L

L

G

G

T

T

F

W

G

K

S

S

D

P

N

-

Y

-

N

-

A

P

N

G

Q

K

I

V

A

T

E

E

A

A

V

V

D

K

F

V

A

A

I

I

R

D

K

L

G

G

Y

Y

R

R

H

H

I

I

D

D

C

C

A

A

S

H

V

V

Y

Y

M

Q

N

N

E

E

P

N

E

E

I

V

G

G

N

L

A

A

I

L

S

Q

G

A

L

K

L

L

N

Q

E

E

G

K

V

V

K

K

R

R

E

E

E

D

L

L

W

F

V

I

T

V

S

S

K

K

V

L

W

W

N

C

D

T

A

Y

H

H

D

D

E

K

-

D

-

L

V

V

V

K

E

G

S

A

C

C

K

Q

K

K

S

T

L

L

N

S

D

D

L

L

K

K

L

L

D

D

Y

Y

L

L

D

D

L

L

Y

Y

L

L

V

I

H

H

W

W

P

-

F

-

P

P

N

T

Y

G

H

F

A

K

P

P

G

G

C

K

D

D

G

F

D

F

A

P

R

L

N

D

P

E

D

D

S

G

R

N

P

V

Y

I

N

P

H

S

E

E

K

K

-

D

Y

F

M

V

E

D

T

T

W

W

R

T

Q

A

M

M

E

E

K

E

L

L

V

V

E

D

M

E

G

G

L

L

V

V

K

K

S

A

I

I

G

G

T

V

S

S

N

N

M

F

T

N

I

H

P

L

K

Q

M

V

E

E

L

K

L

I

L

L

R

N

D

K

A

P

-

G

-

L

K

K

I

Y

K

K

P

P

V

A

V

V

N

N

E

Q

M

I

E

E

L

C

H

H

P

P

H

Y

F

L

Q

T

Q

Q

S

E

E

K

L

L

F

I

N

Q

Y

Y

L

C

A

N

E

S

R

K

N

G

I

I

Q

V

P

V

I

T

G

A

Y

Y

S

S

P

P

I

L

G

G

S

S

P

P

K

D

R

R

P

P

E

W

R

-

D

-

R

A

T

K

K

P

E

E

D

D

T

P

V

S

D

I

I

L

E

E

D

D

P

P

V

R

I

I

V

K

K

A

V

I

A

A

E

D

R

K

L

Y

N

N

L

K

H

T

P

T

A

A

E

Q

V

V

C

L

I

I

K

R

W

F

G

P

V

I

Q

Q

R

R

G

N

E

L

V

I

V

V

I

I

P

P

F

K

S

S

V

V

S

T

P

P

A

E

K

R

I

I

V

A

N

E

N

N

L

F

K

Q

A

V

V

F

T

D

G

F

E

E

S

-

I

L

T

D

N

K

E

E

E

D

M

M

K

N

Q

T

I

L

A

L

G

S

I

Y

D

N

K

R

N

D

C

W

R

R

Sites not aligning to the query:

1 modified: N-acetylalanine

4qxiA Crystal structure of human ar complexed with NADP+ and ak198 (see paper)
43% identity, 88% coverage: 16:313/339 of query aligns to 4:298/314 of 4qxiA

query
sites
4qxiA

K

R

V

I

T

L

L

L

S

N

N

N

G

G

A

A

K

K

I

M

P

P

V

I

L

L

G

G

L

L

G
|
G

T
|
T

F
x
W

G
x
K

S

S

D

P

N

-

Y

-

N

-

A

P

N

G

Q

Q

I

V

A

T

E

E

A

A

V

V

D

K

F

V

A

A

I

I

R

D

K

V

G

G

Y

Y

R

R

H

H

I

I

D
|
D

C

C

A

A

S

H

V
|
V

Y
|
Y

M

Q

N

N

E

E

P

N

E

E

I

V

G

G

N

V

A

A

I

I

S

Q

G

E

L

K

L

L

N

R

E

E

G

Q

V

V

K

K

R

R

E

E

L

L

W

F

V

I

T

V

S

S

K
|
K

V

L

W

W

N

C

D

T

A

Y

H

H

D

E

E

K

-

G

-

L

V

V

V

K

E

G

S

A

C

C

K

Q

K

K

S

T

L

L

N

S

D

D

L

L

K

K

L

L

D

D

Y

Y

L

L

D

D

L

L

Y

Y

L

L

V

I

H
|
H

W
|
W

P

-

F

-

P

P

N

T

Y

G

H

F

A

K

P

P

G

G

C

K

D

E

-

F

-
x
F

-

P

-

L

-

D

-

E

-

S

G

G

D

N

A

V

R

V

N

P

P

S

D

D

S

T

R

N

P

-

Y

-

N

-

H

-

E

-

K

-

Y

I

M

L

E

D

T

T

W

W

R

A

Q

A

M

M

E

E

K

E

L

L

V

V

E

D

M

E

G

G

L

L

V

V

K

K

S

A

I

I

G

G

T

I

S

S

N
|
N

M

F

T

N

I

H

P

L

K

Q

M

V

E

E

L

M

L

I

L

L

R

N

D

K

A

P

-

G

-

L

K

K

I

Y

K

K

P

P

V

A

V

V

N

N

E
x
Q

M

I

E

E

L

C

H

H

P

P

H

Y

F

L

Q

T

Q

Q

S

E

E

K

L

L

F

I

N

Q

Y

Y

L

C

A

Q

E

S

R

K

N

G

I

I

Q

V

P

V

I

T

G

A

Y
|
Y

S
|
S

P
|
P

I
x
L

G

G

S
|
S

P
|
P

K
x
D

R

R

P

P

E

W

R

A

D

K

R

-

T

-

K

P

E

E

D

D

T

P

V

S

D

L

I

L

E

E

D

D

P

P

V

R

I

I

V

K

K

A

V

I

A

A

E

A

R

K

L

H

N

N

L

K

H

T

P

T

A
|
A

E

Q

V

V

C

L

I

I

K

R

W

F

G

P

V

M

Q

Q

R

R

G

N

E

L

V

V

I
|
I

P
|
P

F
x
K

S
|
S

V
|
V

S
x
T

P

P

A

E

K
x
R

I

I

V

A

N
x
E

N
|
N

L

F

K

K

A

V

V

F

T

D

G

F

E

E

S

-

I

L

T

S

N

S

E

Q

E

D

M

M

K

T

Q

T

I

L

A

L

G

S

I

Y

D

N

K

R

N

N

C

W

R

R

L

V

active site: D44 (= D59), Y49 (= Y64), K78 (= K93), H111 (= H124)
binding {2-[(4-amino-2-fluorobenzyl)carbamoyl]-5-chlorophenoxy}acetic acid: W21 (≠ F33), V48 (= V63), Y49 (= Y64), H111 (= H124), W112 (= W125), F123 (vs. gap)
binding nadp nicotinamide-adenine-dinucleotide phosphate: G19 (= G31), T20 (= T32), W21 (≠ F33), K22 (≠ G34), D44 (= D59), Y49 (= Y64), H111 (= H124), N161 (= N175), Q184 (≠ E196), Y210 (= Y222), S211 (= S223), P212 (= P224), L213 (≠ I225), S215 (= S227), P216 (= P228), D217 (≠ K229), A246 (= A260), I261 (= I275), P262 (= P276), K263 (≠ F277), S264 (= S278), V265 (= V279), T266 (≠ S280), R269 (≠ K283), E272 (≠ N286), N273 (= N287)

Sites not aligning to the query:

4q7bA Human aldose reductase complexed with a ligand with an idd structure ([2-(benzylcarbamoyl)-5-fluorophenoxy]acetic acid) at 1.19 a
43% identity, 88% coverage: 16:313/339 of query aligns to 3:297/315 of 4q7bA

query
sites
4q7bA

K

R

V

I

T

L

L

L

S

N

N

N

G

G

A

A

K

K

I

M

P

P

V

I

L

L

G

G

L

L

G
|
G

T
|
T

F
x
W

G
x
K

S

S

D

P

N

-

Y

-

N

-

A

P

N

G

Q

Q

I

V

A

T

E

E

A

A

V

V

D

K

F

V

A

A

I

I

R

D

K

V

G

G

Y

Y

R

R

H

H

I

I

D
|
D

C

C

A

A

S

H

V

V

Y
|
Y

M

Q

N

N

E

E

P

N

E

E

I

V

G

G

N

V

A

A

I

I

S

Q

G

E

L

K

L

L

N

R

E

E

G

Q

V

V

K

K

R

R

E

E

L

L

W

F

V

I

T

V

S

S

K
|
K

V

L

W
|
W

N

C

D

T

A

Y

H

H

D

E

E

K

-

G

-

L

V

V

V

K

E

G

S

A

C

C

K

Q

K

K

S

T

L

L

N

S

D

D

L

L

K

K

L

L

D

D

Y

Y

L

L

D

D

L

L

Y

Y

L

L

V

I

H
|
H

W
|
W

P

-

F

-

P

P

N

T

Y

G

H

F

A

K

P

P

G

G

C

K

D

E

-

F

-
x
F

-

P

-

L

-

D

-

E

-

S

G

G

D

N

A

V

R

V

N

P

P

S

D

D

S

T

R

N

P

-

Y

-

N

-

H

-

E

-

K

-

Y

I

M

L

E

D

T

T

W

W

R

A

Q

A

M

M

E

E

K

E

L

L

V

V

E

D

M

E

G

G

L

L

V

V

K

K

S

A

I

I

G

G

T

I

S

S

N
|
N

M

F

T

N

I

H

P

L

K

Q

M

V

E

E

L

M

L

I

L

L

R

N

D

K

A

P

-

G

-

L

K

K

I

Y

K

K

P

P

V

A

V

V

N

N

E
x
Q

M

I

E

E

L

C

H

H

P

P

H

Y

F

L

Q

T

Q

Q

S

E

E

K

L

L

F

I

N

Q

Y

Y

L

C

A

Q

E

S

R

K

N

G

I

I

Q

V

P

V

I

T

G

A

Y
|
Y

S
|
S

P
|
P

I
x
L

G

G

S
|
S

P
|
P

K
x
D

R

R

P

P

E

W

R

A

D

K

R

-

T

-

K

P

E

E

D

D

T

P

V

S

D

L

I

L

E

E

D

D

P

P

V

R

I

I

V

K

K

A

V

I

A

A

E

A

R

K

L

H

N

N

L

K

H

T

P

T

A
|
A

E

Q

V

V

C

L

I

I

K

R

W

F

G

P

V

M

Q

Q

R

R

G

N

E

L

V

V

I
|
I

P
|
P

F
x
K

S
|
S

V
|
V

S
x
T

P

P

A

E

K
x
R

I

I

V

A

N
x
E

N
|
N

L

F

K

K

A

V

V

F

T

D

G

F

E

E

S

-

I

L

T

S

N

S

E

Q

E

D

M

M

K

T

Q

T

I

L

A

L

G

S

I

Y

D

N

K

R

N

N

C

W

R

R

L

V

active site: D43 (= D59), Y48 (= Y64), K77 (= K93), H110 (= H124)
binding [2-(benzylcarbamoyl)-5-fluorophenoxy]acetic acid: W20 (≠ F33), Y48 (= Y64), W79 (= W95), H110 (= H124), W111 (= W125), F122 (vs. gap)
binding nadp nicotinamide-adenine-dinucleotide phosphate: G18 (= G31), T19 (= T32), W20 (≠ F33), K21 (≠ G34), D43 (= D59), Y48 (= Y64), H110 (= H124), N160 (= N175), Q183 (≠ E196), Y209 (= Y222), S210 (= S223), P211 (= P224), L212 (≠ I225), S214 (= S227), P215 (= P228), D216 (≠ K229), A245 (= A260), I260 (= I275), P261 (= P276), K262 (≠ F277), S263 (= S278), V264 (= V279), T265 (≠ S280), R268 (≠ K283), E271 (≠ N286), N272 (= N287)

4prrA Human aldose reductase complexed with schl7815 ((3-[3-(5-nitrofuran-2- yl)phenyl]propanoic acid)at 1.01 a
43% identity, 88% coverage: 16:313/339 of query aligns to 3:297/315 of 4prrA

query
sites
4prrA

K

R

V

I

T

L

L

L

S

N

N

N

G

G

A

A

K

K

I

M

P

P

V

I

L

L

G

G

L

L

G
|
G

T
|
T

F
x
W

G
x
K

S

S

D

P

N

-

Y

-

N

-

A

P

N

G

Q

Q

I

V

A

T

E

E

A

A

V

V

D

K

F

V

A

A

I

I

R

D

K

V

G

G

Y

Y

R

R

H

H

I

I

D
|
D

C

C

A

A

S

H

V

V

Y
|
Y

M

Q

N

N

E

E

P

N

E

E

I

V

G

G

N

V

A

A

I

I

S

Q

G

E

L

K

L

L

N

R

E

E

G

Q

V

V

K

K

R

R

E

E

L

L

W

F

V

I

T

V

S

S

K
|
K

V

L

W

W

N

C

D

T

A

Y

H

H

D

E

E

K

-

G

-

L

V

V

V

K

E

G

S

A

C

C

K

Q

K

K

S

T

L

L

N

S

D

D

L

L

K

K

L

L

D

D

Y

Y

L

L

D

D

L

L

Y

Y

L

L

V

I

H
|
H

W
|
W

P

-

F

-

P

P

N

T

Y

G

H

F

A

K

P

P

G

G

C

K

D

E

-

F

-

P

-

L

-

D

-

E

-

S

G

G

D

N

A

V

R

V

N

P

P

S

D

D

S

T

R

N

P

-

Y

-

N

-

H

-

E

-

K

-

Y

I

M

L

E

D

T

T

W

W

R

A

Q

A

M

M

E

E

K

E

L

L

V

V

E

D

M

E

G

G

L

L

V

V

K

K

S

A

I

I

G

G

T

I

S

S

N
|
N

M

F

T

N

I

H

P

L

K

Q

M

V

E

E

L

M

L

I

L

L

R

N

D

K

A

P

-

G

-

L

K

K

I

Y

K

K

P

P

V

A

V

V

N

N

E
x
Q

M

I

E

E

L

C

H

H

P

P

H

Y

F

L

Q

T

Q

Q

S

E

E

K

L

L

F

I

N

Q

Y

Y

L

C

A

Q

E

S

R

K

N

G

I

I

Q

V

P

V

I

T

G

A

Y
|
Y

S
|
S

P
|
P

I
x
L

G

G

S
|
S

P
|
P

K
x
D

R

R

P

P

E
x
W

R

A

D

K

R

-

T

-

K

P

E

E

D

D

T

P

V

S

D

L

I

L

E

E

D

D

P

P

V

R

I

I

V

K

K

A

V

I

A

A

E

A

R

K

L

H

N

N

L

K

H

T

P

T

A
|
A

E

Q

V

V

C

L

I

I

K

R

W

F

G

P

V

M

Q

Q

R

R

G

N

E

L

V

V

I
|
I

P
|
P

F
x
K

S
|
S

V
|
V

S
x
T

P

P

A

E

K
x
R

I

I

V

A

N
x
E

N
|
N

L

F

K

K

A

V

V

F

T

D

G

F

E

E

S

-

I

L

T

S

N

S

E

Q

E

D

M

M

K

T

Q

T

I

L

A

L

G

S

I

Y

D

N

K

R

N

N

C

W

R

R

L

V

active site: D43 (= D59), Y48 (= Y64), K77 (= K93), H110 (= H124)
binding 3-[3-(5-nitrofuran-2-yl)phenyl]propanoic acid: W20 (≠ F33), Y48 (= Y64), H110 (= H124), W111 (= W125), W219 (≠ E232)
binding nadp nicotinamide-adenine-dinucleotide phosphate: G18 (= G31), T19 (= T32), W20 (≠ F33), K21 (≠ G34), D43 (= D59), Y48 (= Y64), H110 (= H124), N160 (= N175), Q183 (≠ E196), Y209 (= Y222), S210 (= S223), P211 (= P224), L212 (≠ I225), S214 (= S227), P215 (= P228), D216 (≠ K229), A245 (= A260), I260 (= I275), P261 (= P276), K262 (≠ F277), S263 (= S278), V264 (= V279), T265 (≠ S280), R268 (≠ K283), E271 (≠ N286), N272 (= N287)

Sites not aligning to the query:

4pr4A Human aldose reductase complexed with schl7802 at 1.06 a
43% identity, 88% coverage: 16:313/339 of query aligns to 3:297/315 of 4pr4A

query
sites
4pr4A

K

R

V

I

T

L

L

L

S

N

N

N

G

G

A

A

K

K

I

M

P

P

V

I

L

L

G

G

L

L

G
|
G

T
|
T

F
x
W

G
x
K

S

S

D

P

N

-

Y

-

N

-

A

P

N

G

Q

Q

I

V

A

T

E

E

A

A

V

V

D

K

F

V

A

A

I

I

R

D

K

V

G

G

Y

Y

R

R

H

H

I

I

D
|
D

C

C

A

A

S

H

V

V

Y
|
Y

M

Q

N

N

E

E

P

N

E

E

I

V

G

G

N

V

A

A

I

I

S

Q

G

E

L

K

L

L

N

R

E

E

G

Q

V

V

K

K

R

R

E

E

L

L

W

F

V

I

T

V

S

S

K
|
K

V

L

W

W

N

C

D

T

A

Y

H

H

D

E

E

K

-

G

-

L

V

V

V

K

E

G

S

A

C

C

K

Q

K

K

S

T

L

L

N

S

D

D

L

L

K

K

L

L

D

D

Y

Y

L

L

D

D

L

L

Y

Y

L

L

V

I

H
|
H

W
|
W

P

-

F

-

P

P

N

T

Y

G

H

F

A

K

P

P

G

G

C

K

D

E

-

F

-

P

-

L

-

D

-

E

-

S

G

G

D

N

A

V

R

V

N

P

P

S

D

D

S

T

R

N

P

-

Y

-

N

-

H

-

E

-

K

-

Y

I

M

L

E

D

T

T

W

W

R

A

Q

A

M

M

E

E

K

E

L

L

V

V

E

D

M

E

G

G

L

L

V

V

K

K

S

A

I

I

G

G

T

I

S

S

N
|
N

M

F

T

N

I

H

P

L

K

Q

M

V

E

E

L

M

L

I

L

L

R

N

D

K

A

P

-

G

-

L

K

K

I

Y

K

K

P

P

V

A

V

V

N

N

E
x
Q

M

I

E

E

L

C

H

H

P

P

H

Y

F

L

Q

T

Q

Q

S

E

E

K

L

L

F

I

N

Q

Y

Y

L

C

A

Q

E

S

R

K

N

G

I

I

Q

V

P

V

I

T

G

A

Y
|
Y

S
|
S

P
|
P

I
x
L

G

G

S
|
S

P
|
P

K
x
D

R

R

P

P

E
x
W

R

A

D

K

R

-

T

-

K

P

E

E

D

D

T

P

V

S

D

L

I

L

E

E

D

D

P

P

V

R

I

I

V

K

K

A

V

I

A

A

E

A

R

K

L

H

N

N

L

K

H

T

P

T

A
|
A

E

Q

V

V

C

L

I

I

K

R

W

F

G

P

V

M

Q

Q

R

R

G

N

E

L

V

V

I
|
I

P
|
P

F
x
K

S
|
S

V
|
V

S
x
T

P

P

A

E

K
x
R

I

I

V

A

N
x
E

N
|
N

L

F

K

K

A

V

V

F

T

D

G

F

E

E

S

-

I

L

T

S

N

S

E

Q

E

D

M

M

K

T

Q

T

I

L

A

L

G

S

I

Y

D

N

K

R

N

N

C

W

R

R

L

V

active site: D43 (= D59), Y48 (= Y64), K77 (= K93), H110 (= H124)
binding 3-(3'-nitrobiphenyl-3-yl)propanoic acid: W20 (≠ F33), Y48 (= Y64), H110 (= H124), W111 (= W125), W219 (≠ E232)
binding nadp nicotinamide-adenine-dinucleotide phosphate: G18 (= G31), T19 (= T32), W20 (≠ F33), K21 (≠ G34), D43 (= D59), Y48 (= Y64), H110 (= H124), N160 (= N175), Q183 (≠ E196), Y209 (= Y222), S210 (= S223), P211 (= P224), L212 (≠ I225), S214 (= S227), P215 (= P228), D216 (≠ K229), A245 (= A260), I260 (= I275), P261 (= P276), K262 (≠ F277), S263 (= S278), V264 (= V279), T265 (≠ S280), R268 (≠ K283), E271 (≠ N286), N272 (= N287)

Sites not aligning to the query:

4gcaA Complex of aldose reductase with inhibitor idd 1219
43% identity, 88% coverage: 16:313/339 of query aligns to 3:297/315 of 4gcaA

query
sites
4gcaA

K

R

V

I

T

L

L

L

S

N

N

N

G

G

A

A

K

K

I

M

P

P

V

I

L

L

G

G

L

L

G
|
G

T
|
T

F
x
W

G
x
K

S

S

D

P

N

-

Y

-

N

-

A

P

N

G

Q

Q

I

V

A

T

E

E

A

A

V

V

D

K

F

V

A

A

I

I

R

D

K

V

G

G

Y

Y

R

R

H

H

I

I

D
|
D

C

C

A

A

S

H

V

V

Y
|
Y

M

Q

N

N

E

E

P

N

E

E

I

V

G

G

N

V

A

A

I

I

S

Q

G

E

L

K

L

L

N

R

E

E

G

Q

V

V

K

K

R

R

E

E

L

L

W

F

V

I

T

V

S

S

K
|
K

V

L

W

W

N

C

D

T

A

Y

H

H

D

E

E

K

-

G

-

L

V

V

V

K

E

G

S

A

C

C

K

Q

K

K

S

T

L

L

N

S

D

D

L

L

K

K

L

L

D

D

Y

Y

L

L

D

D

L

L

Y

Y

L

L

V

I

H
|
H

W
|
W

P

-

F

-

P

P

N

T

Y

G

H
x
F

A

K

P

P

G

G

C

K

D

E

-

F

-
x
F

-

P

-

L

-

D

-

E

-

S

G

G

D

N

A

V

R

V

N

P

P

S

D

D

S

T

R

N

P

-

Y

-

N

-

H

-

E

-

K

-

Y

I

M

L

E

D

T

T

W

W

R

A

Q

A

M

M

E

E

K

E

L

L

V

V

E

D

M

E

G

G

L

L

V

V

K

K

S

A

I

I

G

G

T

I

S

S

N
|
N

M

F

T

N

I

H

P

L

K

Q

M

V

E

E

L

M

L

I

L

L

R

N

D

K

A

P

-

G

-

L

K

K

I

Y

K

K

P

P

V

A

V

V

N

N

E
x
Q

M

I

E

E

L

C

H

H

P

P

H

Y

F

L

Q

T

Q

Q

S

E

E

K

L

L

F

I

N

Q

Y

Y

L

C

A

Q

E

S

R

K

N

G

I

I

Q

V

P

V

I

T

G

A

Y
|
Y

S
|
S

P
|
P

I
x
L

G

G

S
|
S

P
|
P

K
x
D

R

R

P

P

E
x
W

R

A

D

K

R

-

T

-

K

P

E

E

D

D

T

P

V

S

D

L

I

L

E

E

D

D

P

P

V

R

I

I

V

K

K

A

V

I

A

A

E

A

R

K

L

H

N

N

L

K

H

T

P

T

A
|
A

E

Q

V

V

C

L

I

I

K

R

W

F

G

P

V

M

Q

Q

R

R

G

N

E

L

V

V

I
|
I

P
|
P

F
x
K

S
|
S

V

V

S
x
T

P

P

A

E

K
x
R

I

I

V

A

N
x
E

N
|
N

L

F

K

K

A

V

V

F

T

D

G

F

E

E

S

-

I

L

T

S

N

S

E

Q

E

D

M

M

K

T

Q

T

I

L

A

L

G

S

I

Y

D

N

K

R

N

N

C

W

R

R

L

V

active site: D43 (= D59), Y48 (= Y64), K77 (= K93), H110 (= H124)
binding {2,6-dimethyl-5-[(4,5,7-trifluoro-1,3-benzothiazol-2-yl)methyl]pyridin-3-yl}acetic acid: W20 (≠ F33), Y48 (= Y64), H110 (= H124), W111 (= W125), F115 (≠ H131), F122 (vs. gap), W219 (≠ E232)
binding nadp nicotinamide-adenine-dinucleotide phosphate: G18 (= G31), T19 (= T32), W20 (≠ F33), K21 (≠ G34), D43 (= D59), Y48 (= Y64), H110 (= H124), W111 (= W125), N160 (= N175), Q183 (≠ E196), Y209 (= Y222), S210 (= S223), P211 (= P224), L212 (≠ I225), S214 (= S227), P215 (= P228), D216 (≠ K229), A245 (= A260), I260 (= I275), P261 (= P276), K262 (≠ F277), S263 (= S278), T265 (≠ S280), R268 (≠ K283), E271 (≠ N286), N272 (= N287)

Sites not aligning to the query:

4rpqA Human aldose reductase complexed with a ligand with an idd structure at 1.20 a (1)
43% identity, 88% coverage: 16:313/339 of query aligns to 2:296/314 of 4rpqA

query
sites
4rpqA

K

R

V

I

T

L

L

L

S

N

N

N

G

G

A

A

K

K

I

M

P

P

V

I

L

L

G

G

L

L

G
|
G

T
|
T

F
x
W

G
x
K

S

S

D

P

N

-

Y

-

N

-

A

P

N

G

Q

Q

I

V

A

T

E

E

A

A

V

V

D

K

F

V

A

A

I

I

R

D

K

V

G

G

Y

Y

R

R

H

H

I

I

D
|
D

C

C

A

A

S

H

V
|
V

Y
|
Y

M

Q

N

N

E

E

P

N

E

E

I

V

G

G

N

V

A

A

I

I

S

Q

G

E

L

K

L

L

N

R

E

E

G

Q

V

V

K

K

R

R

E

E

L

L

W

F

V

I

T

V

S

S

K
|
K

V

L

W
|
W

N

C

D

T

A

Y

H

H

D

E

E

K

-

G

-

L

V

V

V

K

E

G

S

A

C

C

K

Q

K

K

S

T

L

L

N

S

D

D

L

L

K

K

L

L

D

D

Y

Y

L

L

D

D

L

L

Y

Y

L

L

V

I

H
|
H

W
|
W

P

-

F

-

P

P

N
x
T

Y

G

H

F

A

K

P

P

G

G

C

K

D

E

-

F

-
x
F

-

P

-

L

-

D

-

E

-

S

G

G

D

N

A

V

R

V

N

P

P

S

D

D

S

T

R

N

P

-

Y

-

N

-

H

-

E

-

K

-

Y

I

M

L

E

D

T

T

W

W

R

A

Q

A

M

M

E

E

K

E

L

L

V

V

E

D

M

E

G

G

L

L

V

V

K

K

S

A

I

I

G

G

T

I

S

S

N
|
N

M

F

T

N

I

H

P

L

K

Q

M

V

E

E

L

M

L

I

L

L

R

N

D

K

A

P

-

G

-

L

K

K

I

Y

K

K

P

P

V

A

V

V

N

N

E
x
Q

M

I

E

E

L

C

H

H

P

P

H

Y

F

L

Q

T

Q

Q

S

E

E

K

L

L

F

I

N

Q

Y

Y

L

C

A

Q

E

S

R

K

N

G

I

I

Q

V

P

V

I

T

G

A

Y
|
Y

S
|
S

P
|
P

I
x
L

G

G

S
|
S

P
|
P

K
x
D

R

R

P

P

E

W

R

A

D

K

R

-

T

-

K

P

E

E

D

D

T

P

V

S

D

L

I

L

E

E

D

D

P

P

V

R

I

I

V

K

K

A

V

I

A

A

E

A

R

K

L

H

N

N

L

K

H

T

P

T

A
|
A

E

Q

V

V

C

L

I

I

K

R

W

F

G

P

V

M

Q

Q

R

R

G

N

E

L

V

V

I
|
I

P
|
P

F
x
K

S
|
S

V
|
V

S
x
T

P

P

A

E

K
x
R

I

I

V

A

N
x
E

N
|
N

L

F

K

K

A

V

V

F

T

D

G

F

E

E

S

-

I

L

T

S

N

S

E

Q

E

D

M

M

K

T

Q

T

I

L

A

L

G

S

I

Y

D

N

K

R

N

N

C

W

R

R

L

V

active site: D42 (= D59), Y47 (= Y64), K76 (= K93), H109 (= H124)
binding ({3-[(3-nitrobenzyl)carbamoyl]biphenyl-4-yl}oxy)acetic acid: W19 (≠ F33), V46 (= V63), Y47 (= Y64), W78 (= W95), H109 (= H124), W110 (= W125), T112 (≠ N129), F121 (vs. gap)
binding nadp nicotinamide-adenine-dinucleotide phosphate: G17 (= G31), T18 (= T32), W19 (≠ F33), K20 (≠ G34), D42 (= D59), Y47 (= Y64), H109 (= H124), N159 (= N175), Q182 (≠ E196), Y208 (= Y222), S209 (= S223), P210 (= P224), L211 (≠ I225), S213 (= S227), P214 (= P228), D215 (≠ K229), A244 (= A260), I259 (= I275), P260 (= P276), K261 (≠ F277), S262 (= S278), V263 (= V279), T264 (≠ S280), R267 (≠ K283), E270 (≠ N286), N271 (= N287)

Sites not aligning to the query:

binding ({3-[(3-nitrobenzyl)carbamoyl]biphenyl-4-yl}oxy)acetic acid: 299, 302, 308

4nkcA Human aldose reductase complexed with schl7764 at 1.12 a
43% identity, 88% coverage: 16:313/339 of query aligns to 2:296/314 of 4nkcA

query
sites
4nkcA

K

R

V

I

T

L

L

L

S

N

N

N

G

G

A

A

K

K

I

M

P

P

V

I

L

L

G

G

L

L

G
|
G

T
|
T

F
x
W

G
x
K

S

S

D

P

N

-

Y

-

N

-

A

P

N

G

Q

Q

I

V

A

T

E

E

A

A

V

V

D

K

F

V

A

A

I

I

R

D

K

V

G

G

Y

Y

R

R

H

H

I

I

D
|
D

C

C

A

A

S

H

V

V

Y
|
Y

M

Q

N

N

E

E

P

N

E

E

I

V

G

G

N

V

A

A

I

I

S

Q

G

E

L

K

L

L

N

R

E

E

G

Q

V

V

K

K

R

R

E

E

L

L

W

F

V

I

T

V

S

S

K
|
K

V

L

W
|
W

N

C

D

T

A

Y

H

H

D

E

E

K

-

G

-

L

V

V

V

K

E

G

S

A

C

C

K

Q

K

K

S

T

L

L

N

S

D

D

L

L

K

K

L

L

D

D

Y

Y

L

L

D

D

L

L

Y

Y

L

L

V

I

H
|
H

W
|
W

P

-

F

-

P

P

N

T

Y

G

H

F

A

K

P

P

G

G

C

K

D

E

-

F

-
x
F

-

P

-

L

-

D

-

E

-

S

G

G

D

N

A

V

R

V

N

P

P

S

D

D

S

T

R

N

P

-

Y

-

N

-

H

-

E

-

K

-

Y

I

M

L

E

D

T

T

W

W

R

A

Q

A

M

M

E

E

K

E

L

L

V

V

E

D

M

E

G

G

L

L

V

V

K

K

S

A

I

I

G

G

T

I

S

S

N
|
N

M

F

T

N

I

H

P

L

K

Q

M

V

E

E

L

M

L

I

L

L

R

N

D

K

A

P

-

G

-

L

K

K

I

Y

K

K

P

P

V

A

V

V

N

N

E
x
Q

M

I

E

E

L

C

H

H

P

P

H

Y

F

L

Q

T

Q

Q

S

E

E

K

L

L

F

I

N

Q

Y

Y

L

C

A

Q

E

S

R

K

N

G

I

I

Q

V

P

V

I

T

G

A

Y
|
Y

S
|
S

P
|
P

I
x
L

G

G

S
|
S

P
|
P

K
x
D

R

R

P

P

E
x
W

R

A

D

K

R

-

T

-

K

P

E

E

D

D

T

P

V

S

D

L

I

L

E

E

D

D

P

P

V

R

I

I

V

K

K

A

V

I

A

A

E

A

R

K

L

H

N

N

L

K

H

T

P

T

A
|
A

E

Q

V

V

C

L

I

I

K

R

W

F

G

P

V

M

Q

Q

R

R

G

N

E

L

V

V

I
|
I

P
|
P

F
x
K

S
|
S

V
|
V

S
x
T

P

P

A

E

K
x
R

I

I

V

A

N
x
E

N
|
N

L

F

K

K

A

V

V

F

T

D

G

F

E

E

S

-

I

L

T

S

N

S

E

Q

E

D

M

M

K

T

Q

T

I

L

A

L

G

S

I

Y

D

N

K

R

N

N

C

W

R

R

L

V

active site: D42 (= D59), Y47 (= Y64), K76 (= K93), H109 (= H124)
binding (2Z)-3-(3'-nitrobiphenyl-3-yl)prop-2-enoic acid: W19 (≠ F33), Y47 (= Y64), W78 (= W95),