SitesBLAST

O88844 Isocitrate dehydrogenase [NADP] cytoplasmic; IDH; IDH1; Cytosolic NADP-isocitrate dehydrogenase; IDPc; NADP(+)-specific ICDH; Oxalosuccinate decarboxylase; EC 1.1.1.42 from Mus musculus (Mouse) (see paper)
69% identity, 98% coverage: 10:405/405 of query aligns to 10:410/414 of O88844

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O88844

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TIT 75:77 (= TIT 75:77) binding NADP(+)
T77 (= T77) binding in other chain
R82 (= R82) binding NADP(+)
94:100 (vs. 94:100, 100% identical) binding in other chain
R109 (= R109) binding in other chain
R132 (= R132) binding in other chain
K212 (= K212) binding substrate
C245 (≠ T245) mutation to S: No effect on inhibition by cadmium ions.
K260 (= K260) binding NADP(+)
GTVTRH 310:315 (= GTVTRH 310:315) binding NADP(+)
N328 (= N328) binding NADP(+)
C379 (≠ L379) mutation to S: Decreased inhibition by cadmium ions.

5yziA Crystal structure of mouse cytosolic isocitrate dehydrogenase complexed with cadmium (see paper)
69% identity, 98% coverage: 10:405/405 of query aligns to 7:407/409 of 5yziA

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5yziA

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binding cadmium ion: D272 (= D275), D276 (= D279)
binding nadp nicotinamide-adenine-dinucleotide phosphate: T72 (= T75), T74 (= T77), N93 (= N96), H306 (= H309), G307 (= G310), T308 (= T311), V309 (= V312), T310 (= T313), R311 (= R314), H312 (= H315), T324 (= T327), N325 (= N328)

1t09A Crystal structure of human cytosolic NADP(+)-dependent isocitrate dehydrogenase in complex NADP (see paper)
67% identity, 100% coverage: 1:405/405 of query aligns to 1:410/414 of 1t09A

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1t09A

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binding nadp nicotinamide-adenine-dinucleotide phosphate: A74 (= A74), T75 (= T75), I76 (= I76), T77 (= T77), R82 (= R82), N96 (= N96), D279 (= D279), S280 (≠ T280), H309 (= H309), G310 (= G310), V312 (= V312), R314 (= R314), T327 (= T327), N328 (= N328)

O75874 Isocitrate dehydrogenase [NADP] cytoplasmic; IDH; IDH1; Cytosolic NADP-isocitrate dehydrogenase; IDPc; NADP(+)-specific ICDH; Oxalosuccinate decarboxylase; EC 1.1.1.42 from Homo sapiens (Human) (see 6 papers)
67% identity, 100% coverage: 1:405/405 of query aligns to 1:410/414 of O75874

query
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O75874

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D

L

L

K

H

Y

S

Y

Y

D

D

L

L

G

G

I

I

E

E

E

N

R

R

D

D

R

A

T

T

D

N

D

D

Q

Q

I

V

T

T

V

K

D

D

A

A

N

E

A

A

I

I

K

K

Q

K

Y

H

G

N

A

V

G

G

V

V

K

K

C

C

A

A

T
|
T

I
|
I

T
|
T

P

P

D

D

E

E

A

K

R
|
R

V

V

E

E

F

F

G

K

L

L

K

K

K

Q

M

M

W

W

R

K

S
|
S

P
|
P

N
|
N

G
|
G

T
|
T

I
|
I

R
|
R

N

N

I

I

L

L

G

G

V

T

V

V

F

F

R
|
R

E

E

P

A

I

I

C

C

Q

K

N

N

V

I

P

P

R

R

L

L

V

V

P

S

G

G

W

W

T

V

Q

K

P

P

I

I

G

G

R
|
R

H

H

A

A

H

Y

G

G

D

D

Q

Q

Y

Y

K

R

A

A

S

T

D

D

F

F

K

V

V

V

P

P

G

G

P

P

G

G

T

K

V

V

T

E

I

I

T

T

Y

Y

T

T

P

P

E

S

D

D

G

G

G

T

E

Q

P

K

I

V

E

T

M

Y

E

L

V

V

A

H

S

N

F

F

P

E

E

E

G

G

V

V

A

A

M

M

G

G

M

M

Y

Y

N

N

F

Q

R

D

K

K

S

S

I

I

E

E

D

D

F

F

A

A

R

H

A

S

S

S

F

F

G

Q

Y

M

G

A

L

L

D

S

R

K

G

G

Y

W

P

P

V

L

Y

Y

L

L

S

S

T

T

K
|
K

N

N

T

T

I

I

L

L

K

K

A

K

Y

Y

D

D

G

G

M

R

F

F

K

K

D

D

V

I

F

F

A

Q

E

E

I

I

Y

Y

E

D

A

K

E

Q

Y

Y

K

K

E

S

K

Q

F

F

E

E

A

A

A

Q

G

K

I

I

T

W

Y

Y

E

E

H

H

R

R

L

L

I

I

D

D

M

M

V

V

A

A

A

Q

A

A

L

M

K
|
K

W

S

E

E

G

G

Y

F

V

I

W

W

A

A

C

C

K

K

N

N

Y

Y

D

D

G

G

D

D

V

V

Q

Q

S

S

D

D

T

S

V

V

A

A

Q

Q

G

G

F

Y

G

G

S

S

L

L

G

G

L

M

M

M

T

T

S

S

V

V

L

L

R

V

T

C

A

P

D

D

G

G

S

K

T

T

V

V

E

E

A

A

E

E

A

A

H

H

G
|
G

T
|
T

V
|
V

T
|
T

R
|
R

H
|
H

Y

Y

R

R

Q

M

H

Y

Q

Q

A

K

G

G

K

Q

P

E

T

T

S

S

T

T

N
|
N

P

P

I

I

A

A

S

S

I

I

F

F

A

A

W

W

T

T

R

R

G

G

L

L

D

A

H

H

R

R

G

A

K

K

L

L

D

D

N

N

T

N

P

K

K

E

V

L

N

A

E

F

F

F

A

A

H

N

A

A

L

L

E

E

D

E

V

V

V

S

V

I

N

E

T

T

V

I

E

E

G

A

G

G

Q

F

M

M

T

T

K

K

D

D

L

L

A

A

L

A

L

C

V

I

G

K

G

G

-

L

-

P

-

N

-

V

-

Q

E

R

Q

S

D

D

W

Y

L

L

T

N

T

T

E

F

Q

E

F

F

L

M

A

D

A

K

L

L

D

G

E

E

N

N

L

L

Q

K

K

I

R

K

L

L

A

A

TIT 75:77 (= TIT 75:77) binding NADP(+)
T77 (= T77) binding in other chain
R82 (= R82) binding NADP(+)
94:100 (vs. 94:100, 100% identical) binding in other chain
R109 (= R109) binding in other chain
R132 (= R132) binding in other chain; to C: in colorectal cancer and glioma samples; glioblastoma multiforme; somatic mutation; found in patients with cartilaginous tumors; abolishes magnesium binding and alters enzyme activity so that isocitrate is no longer converted to alpha-ketoglutarate but instead alpha-ketoglutarate is converted to R(-)-2-hydroxyglutarate; induces histone methylation; enhances expression of chondrocyte-related genes; disturbs the formation of cartilaginous matrix; inhibits osteogenic differentiation; dbSNP:rs121913499; to G: in a glioma sample; glioblastoma multiforme; somatic mutation; found in patients with cartilaginous tumors; dbSNP:rs121913499; to H: in a glioma sample; glioblastoma multiforme; somatic mutation; found in patients with cartilaginous tumors; abolishes magnesium binding and alters enzyme activity so that isocitrate is no longer converted to alpha-ketoglutarate but instead alpha-ketoglutarate is converted to R(-)-2-hydroxyglutarate; dbSNP:rs121913500; to L: in a glioma sample; glioblastoma multiforme; somatic mutation; abolishes magnesium binding and alters enzyme activity so that isocitrate is no longer converted to alpha-ketoglutarate but instead alpha-ketoglutarate is converted to R(-)-2-hydroxyglutarate; dbSNP:rs121913500; to S: in a glioma sample; glioblastoma multiforme; somatic mutation; abolishes magnesium binding and alters enzyme activity so that isocitrate is no longer converted to alpha-ketoglutarate but instead alpha-ketoglutarate is converted to R(-)-2-hydroxyglutarate; dbSNP:rs121913499
K212 (= K212) binding substrate
K260 (= K260) binding NADP(+)
GTVTRH 310:315 (= GTVTRH 310:315) binding NADP(+)
N328 (= N328) binding NADP(+)

6bkxA Novel modes of inhibition of wild-type idh1: direct covalent modification of his315 with cmpd1 (see paper)
68% identity, 98% coverage: 10:405/405 of query aligns to 8:408/414 of 6bkxA

query
sites
6bkxA

V

V

E

E

L

M

D

Q

G

G

D

D

E

E

M

M

T

T

R

R

I

I

W

W

S

E

F

L

I

I

K

K

D

E

R

K

L

L

I

I

L

F

P

P

Y

Y

L

V

D

E

V

L

D

D

L

L

K

H

Y

S

Y

Y

D

D

L

L

G

G

I

I

E

E

E

N

R

R

D

D

R

A

T

T

D

N

D

D

Q

Q

I

V

T

T

V

K

D

D

A

A

N

E

A

A

I

I

K

K

Q

K

Y

H

G

N

A

V

G

G

V

V

K

K

C

C

A

A

T

T

I

I

T

T

P

P

D

D

E

E

A

K

R

R

V

V

E

E

F

F

G

K

L

L

K

K

K

Q

M

M

W

W

R

K

S

S

P

P

N

N

G

G

T

T

I

I

R

R

N

N

I

I

L

L

G

G

V

T

V

V

F

F

R

R

E

E

P

A

I

I

C

C

Q

K

N

N

V

I

P

P

R

R

L

L

V

V

P

S

G

G

W

W

T

V

Q

K

P

P

I

I

G

G

R

R

H

H

A

A

H

Y

G

G

D

D

Q

Q

Y

Y

K

R

A

A

S

T

D

D

F

F

K

V

V

V

P

P

G

G

P

P

G

G

T

K

V

V

T

E

I

I

T

T

Y

Y

T

T

P

P

E

S

D

D

G

G

G

T

E

Q

P

K

I

V

E

T

M

Y

E

L

V

V

A

H

S

N

F

F

P

E

E

E

G

G

V

V

A

A

M

M

G

G

M

M

Y

Y

N

N

F

Q

R

D

K

K

S

S

I

I

E

E

D

D

F

F

A

A

R

H

A

S

S

S

F

F

G

Q

Y

M

G

A

L

L

D

S

R

K

G

G

Y

W

P

P

V

L

Y

Y

L

L

S

S

T

T

K

K

N

N

T

T

I

I

L

L

K

K

A

K

Y

Y

D

D

G

G

M

R

F

F

K

K

D

D

V

I

F

F

A

Q

E

E

I

I

Y

Y

E

D

A

K

E

Q

Y

Y

K

K

E

S

K

Q

F

F

E

E

A

A

A

Q

G

K

I

I

T

W

Y

Y

E

E

H

H

R

R

L

L

I

I

D

D

M

M

V

V

A

A

A

Q

A

A

L

M

K

K

W

S

E

E

G

G

Y

F

V

I

W

W

A

A

C

C

K

K

N

N

Y

Y

D

D

G

G

D
|
D

V

V

Q

Q

S

S

D
|
D

T

S

V

V

A

A

Q

Q

G

G

F

Y

G

G

S

S

L

L

G

G

L

M

M

M

T

T

S

S

V

V

L

L

R

V

T

C

A

P

D

D

G

G

S

K

T

T

V

V

E

E

A

A

E

E

A

A

H
|
H

G

G

T

T

V
|
V

T

T

R
|
R

H
|
H

Y

Y

R

R

Q

M

H

Y

Q

Q

A

K

G

G

K

Q

P

E

T

T

S
|
S

T

T

N

N

P

P

I

I

A

A

S

S

I

I

F

F

A

A

W

W

T

T

R

R

G

G

L

L

D

A

H

H

R

R

G

A

K

K

L

L

D

D

N

N

T

N

P

K

K

E

V

L

N

A

E

F

F

F

A

A

H

N

A

A

L

L

E

E

D

E

V

V

V

S

V

I

N

E

T

T

V

I

E

E

G

A

G

G

Q

F

M

M

T

T

K
|
K

D
|
D

L

L

A

A

L

A

L

C

V

I

G

K

G

G

-

L

-

P

-

N

-

V

-

Q

E

R

Q

S

D

D

W

Y

L

L

T

N

T

T

E

F

Q

E

F

F

L

M

A

D

A

K

L

L

D

G

E

E

N

N

L

L

Q

K

K

I

R

K

L

L

A

A

binding calcium ion: D273 (= D275), D277 (= D279)
binding (6aS,7S,9R,10aS)-7,10a-dimethyl-8-oxo-2-(phenylamino)-5,6,6a,7,8,9,10,10a-octahydrobenzo[h]quinazoline-9-carbonitrile: H307 (= H309), V310 (= V312), R312 (= R314), H313 (= H315), S324 (= S326), K372 (= K374), D373 (= D375)

6bl2A Novel modes of inhibition of wild-type idh1: direct covalent modification of his315 with cmpd15 (see paper)
68% identity, 98% coverage: 10:405/405 of query aligns to 8:408/416 of 6bl2A

query
sites
6bl2A

V

V

E

E

L

M

D

Q

G

G

D

D

E

E

M

M

T

T

R

R

I

I

W

W

S

E

F

L

I

I

K

K

D

E

R

K

L

L

I

I

L

F

P

P

Y

Y

L

V

D

E

V

L

D

D

L

L

K

H

Y

S

Y

Y

D

D

L

L

G

G

I

I

E

E

E

N

R

R

D

D

R

A

T

T

D

N

D

D

Q

Q

I

V

T

T

V

K

D

D

A

A

N

E

A

A

I

I

K

K

Q

K

Y

H

G

N

A

V

G

G

V

V

K

K

C

C

A

A

T

T

I

I

T

T

P

P

D

D

E

E

A

K

R

R

V

V

E

E

F

F

G

K

L

L

K

K

K

Q

M

M

W

W

R

K

S

S

P

P

N

N

G

G

T

T

I

I

R

R

N

N

I

I

L

L

G

G

V

T

V

V

F

F

R

R

E

E

P

A

I

I

C

C

Q

K

N

N

V

I

P

P

R

R

L

L

V

V

P

S

G

G

W

W

T

V

Q

K

P

P

I

I

G

G

R

R

H

H

A

A

H

Y

G

G

D

D

Q

Q

Y

Y

K

R

A

A

S

T

D

D

F

F

K

V

V

V

P

P

G

G

P

P

G

G

T

K

V

V

T

E

I

I

T

T

Y

Y

T

T

P

P

E

S

D

D

G

G

G

T

E

Q

P

K

I

V

E

T

M

Y

E

L

V

V

A

H

S

N

F

F

P

E

E

E

G

G

V

V

A

A

M

M

G

G

M

M

Y

Y

N

N

F

Q

R

D

K

K

S

S

I

I

E

E

D

D

F

F

A

A

R

H

A

S

S

S

F

F

G

Q

Y

M

G

A

L

L

D

S

R

K

G

G

Y

W

P

P

V

L

Y

Y

L

L

S

S

T

T

K

K

N

N

T

T

I

I

L

L

K

K

A

K

Y

Y

D

D

G

G

M

R

F

F

K

K

D

D

V

I

F

F

A

Q

E

E

I

I

Y

Y

E

D

A

K

E

Q

Y

Y

K

K

E

S

K

Q

F

F

E

E

A

A

A

Q

G

K

I

I

T

W

Y

Y

E

E

H

H

R

R

L

L

I

I

D

D

M

M

V

V

A

A

A

Q

A

A

L

M

K

K

W

S

E

E

G

G

Y

F

V

I

W

W

A

A

C

C

K

K

N

N

Y

Y

D

D

G

G

D

D

V

V

Q

Q

S

S

D

D

T

S

V

V

A

A

Q

Q

G

G

F

Y

G

G

S

S

L

L

G

G

L

M

M

M

T

T

S

S

V

V

L

L

R

V

T

C

A

P

D

D

G

G

S

K

T

T

V

V

E

E

A

A

E

E

A

A

H
|
H

G

G

T

T

V
|
V

T

T

R
|
R

H
|
H

Y

Y

R

R

Q

M

H

Y

Q

Q

A

K

G

G

K

Q

P

E

T
|
T

S

S

T

T

N

N

P

P

I

I

A

A

S

S

I

I

F

F

A

A

W

W

T

T

R

R

G

G

L

L

D

A

H

H

R

R

G

A

K

K

L

L

D

D

N

N

T

N

P

K

K

E

V

L

N

A

E

F

F

F

A

A

H

N

A

A

L

L

E

E

D

E

V

V

V

S

V

I

N

E

T

T

V

I

E

E

G

A

G

G

Q

F

M

M

T

T

K
|
K

D
|
D

L

L

A

A

L
x
A

L

C

V

I

G

K

G

G

-
x
L

-

P

-

N

-

V

-

Q

E

R

Q

S

D

D

W

Y

L

L

T

N

T

T

E

F

Q

E

F

F

L

M

A

D

A

K

L

L

D

G

E

E

N

N

L

L

Q

K

K

I

R

K

L

L

A

A

binding 3-[(6aS,7S,9S,10aS)-9-cyano-7-methyl-8-oxo-2-(phenylamino)-6,6a,7,8,9,10-hexahydrobenzo[h]quinazolin-10a(5H)-yl]benzoic acid: H307 (= H309), V310 (= V312), R312 (= R314), H313 (= H315), T323 (= T325), K372 (= K374), D373 (= D375), A376 (≠ L378), L381 (vs. gap)

6bl1A Novel modes of inhibition of wild-type idh1: direct covalent modification of his315 with cmpd13 (see paper)
68% identity, 98% coverage: 10:405/405 of query aligns to 8:408/416 of 6bl1A

query
sites
6bl1A

V

V

E

E

L

M

D

Q

G

G

D

D

E

E

M

M

T

T

R

R

I

I

W

W

S

E

F

L

I

I

K

K

D

E

R

K

L

L

I

I

L

F

P

P

Y

Y

L

V

D

E

V

L

D

D

L

L

K

H

Y

S

Y

Y

D

D

L

L

G

G

I

I

E

E

E

N

R

R

D

D

R

A

T

T

D

N

D

D

Q

Q

I

V

T

T

V

K

D

D

A

A

N

E

A

A

I

I

K

K

Q

K

Y

H

G

N

A

V

G

G

V

V

K

K

C

C

A

A

T

T

I

I

T

T

P

P

D

D

E

E

A

K

R

R

V

V

E

E

F

F

G

K

L

L

K

K

K

Q

M

M

W

W

R

K

S

S

P

P

N

N

G

G

T

T

I

I

R

R

N

N

I

I

L

L

G

G

V

T

V

V

F

F

R

R

E

E

P

A

I

I

C

C

Q

K

N

N

V

I

P

P

R

R

L

L

V

V

P

S

G

G

W

W

T

V

Q

K

P

P

I

I

G

G

R

R

H

H

A

A

H

Y

G

G

D

D

Q

Q

Y

Y

K

R

A

A

S

T

D

D

F

F

K

V

V

V

P

P

G

G

P

P

G

G

T

K

V

V

T

E

I

I

T

T

Y

Y

T

T

P

P

E

S

D

D

G

G

G

T

E

Q

P

K

I

V

E

T

M

Y

E

L

V

V

A

H

S

N

F

F

P

E

E

E

G

G

V

V

A

A

M

M

G

G

M

M

Y

Y

N

N

F

Q

R

D

K

K

S

S

I

I

E

E

D

D

F

F

A

A

R

H

A

S

S

S

F

F

G

Q

Y

M

G

A

L

L

D

S

R

K

G

G

Y

W

P

P

V

L

Y

Y

L

L

S

S

T

T

K

K

N

N

T

T

I

I

L

L

K

K

A

K

Y

Y

D

D

G

G

M

R

F

F

K

K

D

D

V

I

F

F

A

Q

E

E

I

I

Y

Y

E

D

A

K

E

Q

Y

Y

K

K

E

S

K

Q

F

F

E

E

A

A

A

Q

G

K

I

I

T

W

Y

Y

E

E

H

H

R

R

L

L

I

I

D

D

M

M

V

V

A

A

A

Q

A

A

L

M

K

K

W

S

E

E

G

G

Y

F

V

I

W

W

A

A

C

C

K

K

N

N

Y

Y

D

D

G

G

D
|
D

V

V

Q

Q

S

S

D
|
D

T

S

V

V

A

A

Q

Q

G

G

F

Y

G

G

S

S

L

L

G

G

L

M

M

M

T

T

S

S

V

V

L

L

R

V

T

C

A

P

D

D

G

G

S

K

T

T

V

V

E

E

A

A

E

E

A

A

H
|
H

G

G

T

T

V
|
V

T

T

R
|
R

H
|
H

Y

Y

R

R

Q
x
M

H

Y

Q

Q

A

K

G

G

K

Q

P

E

T

T

S

S

T

T

N

N

P

P

I

I

A

A

S

S

I

I

F

F

A

A

W

W

T

T

R

R

G

G

L

L

D

A

H

H

R

R

G

A

K

K

L

L

D

D

N

N

T

N

P

K

K

E

V

L

N

A

E

F

F

F

A

A

H

N

A

A

L

L

E

E

D

E

V

V

V

S

V

I

N

E

T

T

V

I

E

E

G

A

G

G

Q

F

M

M

T

T

K
|
K

D

D

L

L

A

A

L

A

L

C

V

I

G

K

G

G

-
x
L

-

P

-

N

-

V

-

Q

E

R

Q

S

D

D

W

Y

L

L

T

N

T

T

E

F

Q

E

F

F

L

M

A

D

A

K

L

L

D

G

E

E

N

N

L

L

Q

K

K

I

R

K

L

L

A

A

binding calcium ion: D273 (= D275), D277 (= D279)
binding (6aS,7S,9S,10aS)-7-methyl-8-oxo-10a-phenyl-2-(phenylamino)-5,6,6a,7,8,9,10,10a-octahydrobenzo[h]quinazoline-9-carbonitrile: H307 (= H309), V310 (= V312), R312 (= R314), H313 (= H315), M316 (≠ Q318), K372 (= K374), L381 (vs. gap)

6bl0A Novel modes of inhibition of wild-type idh1:direct covalent modification of his315 with cmpd11 (see paper)
68% identity, 98% coverage: 10:405/405 of query aligns to 8:408/416 of 6bl0A

query
sites
6bl0A

V

V

E

E

L

M

D

Q

G

G

D

D

E

E

M

M

T

T

R

R

I

I

W

W

S

E

F

L

I

I

K

K

D

E

R

K

L

L

I

I

L

F

P

P

Y

Y

L

V

D

E

V

L

D

D

L

L

K

H

Y

S

Y

Y

D

D

L

L

G

G

I

I

E

E

E

N

R

R

D

D

R

A

T

T

D

N

D

D

Q

Q

I

V

T

T

V

K

D

D

A

A

N

E

A

A

I

I

K

K

Q

K

Y

H

G

N

A

V

G

G

V

V

K

K

C

C

A

A

T

T

I

I

T

T

P

P

D

D

E

E

A

K

R

R

V

V

E

E

F

F

G

K

L

L

K

K

K

Q

M

M

W

W

R

K

S

S

P

P

N

N

G

G

T

T

I

I

R

R

N

N

I

I

L

L

G

G

V

T

V

V

F

F

R

R

E

E

P

A

I

I

C

C

Q

K

N

N

V

I

P

P

R

R

L

L

V

V

P

S

G

G

W

W

T

V

Q

K

P

P

I

I

G

G

R

R

H

H

A

A

H

Y

G

G

D

D

Q

Q

Y

Y

K

R

A

A

S

T

D

D

F

F

K

V

V

V

P

P

G

G

P

P

G

G

T

K

V

V

T

E

I

I

T

T

Y

Y

T

T

P

P

E

S

D

D

G

G

G

T

E

Q

P

K

I

V

E

T

M

Y

E

L

V

V

A

H

S

N

F

F

P

E

E

E

G

G

V

V

A

A

M

M

G

G

M

M

Y

Y

N

N

F

Q

R

D

K

K

S

S

I

I

E

E

D

D

F

F

A

A

R

H

A

S

S

S

F

F

G

Q

Y

M

G

A

L

L

D

S

R

K

G

G

Y

W

P

P

V

L

Y

Y

L

L

S

S

T

T

K

K

N

N

T

T

I

I

L

L

K

K

A

K

Y

Y

D

D

G

G

M

R

F

F

K

K

D

D

V

I

F

F

A

Q

E

E

I

I

Y

Y

E

D

A

K

E

Q

Y

Y

K

K

E

S

K

Q

F

F

E

E

A

A

A

Q

G

K

I

I

T

W

Y

Y

E

E

H

H

R

R

L

L

I

I

D

D

M

M

V

V

A

A

A

Q

A

A

L

M

K

K

W

S

E

E

G

G

Y

F

V

I

W

W

A

A

C

C

K

K

N

N

Y

Y

D

D

G

G

D

D

V

V

Q

Q

S

S

D

D

T

S

V

V

A

A

Q

Q

G

G

F

Y

G

G

S

S

L

L

G

G

L

M

M

M

T

T

S

S

V

V

L

L

R

V

T

C

A

P

D

D

G

G

S

K

T

T

V

V

E

E

A

A

E

E

A

A

H
|
H

G

G

T

T

V
|
V

T

T

R
|
R

H
|
H

Y

Y

R

R

Q

M

H

Y

Q

Q

A

K

G

G

K

Q

P

E

T

T

S

S

T

T

N
|
N

P

P

I

I

A

A

S

S

I

I

F

F

A

A

W

W

T

T

R

R

G

G

L

L

D

A

H

H

R

R

G

A

K

K

L

L

D

D

N

N

T

N

P

K

K

E

V

L

N

A

E

F

F

F

A

A

H

N

A

A

L

L

E

E

D

E

V

V

V

S

V

I

N

E

T

T

V

I

E

E

G

A

G

G

Q

F

M

M

T

T

K
|
K

D

D

L

L

A

A

L

A

L

C

V

I

G

K

G

G

-
x
L

-

P

-

N

-

V

-

Q

E

R

Q

S

D

D

W

Y

L

L

T

N

T

T

E

F

Q

E

F

F

L

M

A

D

A

K

L

L

D

G

E

E

N

N

L

L

Q

K

K

I

R

K

L

L

A

A

binding (5aS,6S,8S,9aS)-2-(benzenecarbonyl)-6-methyl-7-oxo-9a-phenyl-4,5,5a,6,7,8,9,9a-octahydro-2H-benzo[g]indazole-8-carbonitrile: H307 (= H309), V310 (= V312), R312 (= R314), H313 (= H315), N326 (= N328), K372 (= K374), L381 (vs. gap)

6bkyA Novel binding modes of inhibition of wild-type idh1: allosteric inhibition with cmpd2 (see paper)
68% identity, 98% coverage: 10:405/405 of query aligns to 8:408/416 of 6bkyA

query
sites
6bkyA

V

V

E

E

L

M

D

Q

G

G

D

D

E

E

M

M

T

T

R

R

I

I

W

W

S

E

F

L

I

I

K

K

D

E

R

K

L

L

I

I

L

F

P

P

Y

Y

L

V

D

E

V

L

D

D

L

L

K

H

Y

S

Y

Y

D

D

L

L

G

G

I

I

E

E

E

N

R

R

D

D

R

A

T

T

D

N

D

D

Q

Q

I

V

T

T

V

K

D

D

A

A

N

E

A

A

I

I

K

K

Q

K

Y

H

G

N

A

V

G

G

V

V

K

K

C

C

A

A

T

T

I

I

T

T

P

P

D

D

E

E

A

K

R

R

V

V

E

E

F

F

G

K

L

L

K

K

K

Q

M

M

W

W

R

K

S

S

P

P

N

N

G

G

T

T

I

I

R

R

N

N

I

I

L

L

G

G

V

T

V

V

F

F

R

R

E

E

P

A

I

I

C

C

Q

K

N

N

V

I

P

P

R

R

L

L

V

V

P

S

G

G

W

W

T

V

Q

K

P

P

I

I

G

G

R

R

H

H

A

A

H

Y

G

G

D

D

Q

Q

Y

Y

K

R

A

A

S

T

D

D

F

F

K

V

V

V

P

P

G

G

P

P

G

G

T

K

V

V

T

E

I

I

T

T

Y

Y

T

T

P

P

E

S

D

D

G

G

G

T

E

Q

P

K

I

V

E

T

M

Y

E

L

V

V

A

H

S

N

F

F

P

E

E

E

G

G

V

V

A

A

M

M

G

G

M

M

Y

Y

N

N

F

Q

R

D

K

K

S

S

I

I

E

E

D

D

F

F

A

A

R

H

A

S

S

S

F

F

G

Q

Y

M

G

A

L

L

D

S

R

K

G

G

Y

W

P

P

V

L

Y

Y

L

L

S

S

T

T

K

K

N

N

T

T

I

I

L

L

K

K

A

K

Y

Y

D

D

G

G

M

R

F

F

K

K

D

D

V

I

F

F

A

Q

E

E

I

I

Y

Y

E

D

A

K

E

Q

Y

Y

K

K

E

S

K

Q

F

F

E

E

A

A

A

Q

G

K

I

I

T

W

Y

Y

E

E

H

H

R

R

L

L

I

I

D

D

M

M

V
|
V

A

A

A

Q

A

A

L
x
M

K

K

W

S

E

E

G

G

Y

F

V

I

W

W

A

A

C

C

K

K

N

N

Y

Y

D

D

G

G

D

D

V

V

Q
|
Q

S

S

D

D

T
x
S

V

V

A

A

Q

Q

G

G

F

Y

G

G

S

S

L

L

G

G

L

M

M

M

T

T

S

S

V

V

L

L

R

V

T

C

A

P

D

D

G

G

S

K

T

T

V

V

E

E

A

A

E

E

A

A

H

H

G

G

T

T

V

V

T

T

R

R

H

H

Y

Y

R

R

Q

M

H

Y

Q

Q

A

K

G

G

K

Q

P

E

T

T

S

S

T

T

N

N

P

P

I

I

A

A

S

S

I

I

F

F

A

A

W

W

T

T

R

R

G

G

L

L

D

A

H

H

R

R

G

A

K

K

L

L

D

D

N

N

T

N

P

K

K

E

V

L

N

A

E

F

F

F

A

A

H

N

A

A

L

L

E

E

D

E

V

V

V

S

V

I

N

E

T

T

V

I

E

E

G

A

G

G

Q

F

M

M

T

T

K

K

D

D

L

L

A

A

L

A

L

C

V

I

G

K

G

G

-

L

-

P

-

N

-

V

-

Q

E

R

Q

S

D

D

W

Y

L

L

T

N

T

T

E

F

Q

E

F

F

L

M

A

D

A

K

L

L

D

G

E

E

N

N

L

L

Q

K

K

I

R

K

L

L

A

A

binding 4,5,6,7-tetrabromo-1h,3h-benzimidazol-2-one: V253 (= V255), M257 (≠ L259), Q275 (= Q277), S278 (≠ T280)

6bkzA Novel modes of inhibition of wild-type idh1: non-equivalent allosteric inhibition with cmpd3 (see paper)
68% identity, 98% coverage: 10:405/405 of query aligns to 8:408/412 of 6bkzA

query
sites
6bkzA

V

V

E

E

L

M

D

Q

G

G

D

D

E

E

M

M

T

T

R

R

I

I

W

W

S

E

F

L

I

I

K

K

D

E

R

K

L

L

I

I

L

F

P

P

Y

Y

L

V

D

E

V

L

D

D

L

L

K

H

Y

S

Y

Y

D

D

L

L

G

G

I

I

E

E

E

N

R

R

D

D

R

A

T

T

D

N

D

D

Q

Q

I

V

T

T

V

K

D

D

A

A

N

E

A

A

I

I

K

K

Q

K

Y

H

G

N

A

V

G

G

V

V

K

K

C

C

A

A

T
|
T

I
|
I

T
|
T

P

P

D

D

E

E

A

K

R

R

V

V

E

E

F

F

G

K

L

L

K

K

K

Q

M

M

W

W

R

K

S

S

P

P

N
|
N

G

G

T

T

I

I

R

R

N

N

I

I

L

L

G

G

V

T

V

V

F

F

R

R

E

E

P
x
A

I

I

I
|
I

C

C

Q

K

N

N

V

I

P

P

R

R

L
|
L

V

V

P

S

G

G

W
|
W

T

V

Q

K

P

P

I
|
I

I

I

G

G

R

R

H

H

A

A

H

Y

G

G

D

D

Q

Q

Y

Y

K

R

A

A

S

T

D

D

F

F

K

V

V

V

P

P

G

G

P

P

G

G

T

K

V

V

T

E

I

I

T

T

Y

Y

T

T

P

P

E

S

D

D

G

G

G

T

E

Q

P

K

I

V

E

T

M

Y

E

L

V

V

A

H

S

N

F

F

P

E

E

E

G

G

V

V

A

A

M

M

G

G

M

M

Y

Y

N

N

F

Q

R

D

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K

S

S

I

I

E

E

D

D

F

F

A

A

R

H

A

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S

S

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F

G

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Y

M

G

A

L

L

D

S

R

K

G

G

Y

W

P

P

V

L

Y

Y

L

L

S

S

T

T

K

K

N

N

T

T

I

I

L

L

K

K

A

K

Y

Y

D

D

G

G

M

R

F

F

K

K

D

D

V

I

F

F

A

Q

E

E

I

I

Y

Y

E

D

A

K

E

Q

Y

Y

K

K

E

S

K

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F

F

E

E

A

A

A

Q

G

K

I

I

T

W

Y

Y

E

E

H

H

R

R

L

L

I

I

D

D

M

M

V

V

A

A

A

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A

A

L
x
M

K

K

W

S

E

E

G

G

Y

F

V

I

W
|
W

A

A

C

C

K

K

N

N

Y

Y

D

D

G

G

D

D

V
|
V

Q

Q

S

S

D

D

T

S

V
|
V

A
|
A

Q

Q

G
|
G

F
x
Y

G

G

S
|
S

L

L

G

G

L

M

M

M

T

T

S

S

V

V

L

L

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V

T

C

A

P

D

D

G

G

S

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T

T

V

V

E

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A

A

E

E

A

A

H
|
H

G
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G

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T

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V

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R

H
|
H

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Y

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R

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H

Y

Q

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A

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E

T

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T
|
T

N
|
N

P

P

I

I

A

A

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S

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I

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F

A

A

W

W

T

T

R

R

G

G

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D

A

H

H

R

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G

A

K

K

L

L

D

D

N

N

T

N

P

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K

E

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L

N

A

E

F

F

F

A

A

H

N

A

A

L

L

E

E

D

E

V

V

V

S

V

I

N

E

T

T

V

I

E

E

G

A

G

G

Q

F

M

M

T

T

K

K

D
|
D

L

L

A

A

L

A

L

C

V

I

G

K

G

G

-

L

-

P

-

N

-

V

-

Q

E

R

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S

D

D

W

Y

L

L

T

N

T

T

E

F

Q

E

F

F

L

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A

D

A

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L

L

D

G

E

E

N

N

L

L

Q

K

K

I

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K

L

L

A

A

binding (7R)-1-[(4-fluorophenyl)methyl]-N-{3-[(1R)-1-hydroxyethyl]phenyl}-7-methyl-5-(1H-pyrrole-2-carbonyl)-4,5,6,7-tetrahydro-1H-pyrazolo[4,3-c]pyridine-3-carboxamide: A109 (≠ P111), I111 (= I113), L118 (= L120), L118 (= L120), W122 (= W124), I126 (= I128), M257 (≠ L259), M257 (≠ L259), W265 (= W267), V274 (= V276), V279 (= V281), A280 (= A282), G282 (= G284), Y283 (≠ F285)
binding nadp nicotinamide-adenine-dinucleotide phosphate: T73 (= T75), I74 (= I76), T75 (= T77), N94 (= N96), S285 (= S287), H307 (= H309), G308 (= G310), T309 (= T311), V310 (= V312), R312 (= R314), H313 (= H315), T325 (= T327), N326 (= N328), D373 (= D375)

5yfmA Human isocitrate dehydrogenase 1 bound with NADP
68% identity, 98% coverage: 10:405/405 of query aligns to 8:408/409 of 5yfmA

query
sites
5yfmA

V

V

E

E

L

M

D

Q

G

G

D

D

E

E

M

M

T

T

R

R

I

I

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W

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L

I

I

K

K

D

E

R

K

L

L

I

I

L

F

P

P

Y

Y

L

V