SitesBLAST

P33198 Isocitrate dehydrogenase [NADP], mitochondrial; IDH; ICD-M; IDP; NADP(+)-specific ICDH; Oxalosuccinate decarboxylase; EC 1.1.1.42 from Sus scrofa (Pig) (see 2 papers)
69% identity, 99% coverage: 3:404/407 of query aligns to 12:419/421 of P33198

query
sites
P33198

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-

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T86 (= T77) binding
103:109 (vs. 94:100, 100% identical) binding
R118 (= R109) binding
R141 (= R132) binding
Y148 (= Y139) Critical for catalysis; mutation to F: Large decrease in Vmax and insignificant change in KM for isocitrate and NADP.
K220 (= K211) Critical for catalysis; mutation K->Q,Y: Large decrease in Vmax and insignificant change in KM for isocitrate and NADP.
D260 (= D251) binding
D283 (= D274) binding

5h3eB Crystal structure of mouse isocitrate dehydrogenases 2 k256q mutant complexed with isocitrate (see paper)
69% identity, 99% coverage: 3:404/407 of query aligns to 2:409/410 of 5h3eB

query
sites
5h3eB

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P

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G

binding magnesium ion: D273 (= D274), D277 (= D278)

P48735 Isocitrate dehydrogenase [NADP], mitochondrial; IDH; ICD-M; IDP; NADP(+)-specific ICDH; Oxalosuccinate decarboxylase; EC 1.1.1.42 from Homo sapiens (Human) (see 4 papers)
69% identity, 99% coverage: 3:404/407 of query aligns to 43:450/452 of P48735

query
sites
P48735

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F

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P

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P

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P

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R

H

H

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A

F

H

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D

D

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A

A

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F

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A

A

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A

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N

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K

D

D

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L

A

A

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C

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H

P

G

-

L

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-

N

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K

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D

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T

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N

N

L

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D

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K

A

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L

A

G

P158 (= P118) to L: in GLM; somatic mutation
P162 (= P122) to S: in GLM; somatic mutation
R172 (= R132) to G: in GLM; somatic mutation; reduces enzymatic activity; dbSNP:rs1057519906; to K: in GLM; somatic mutation; reduces enzymatic activity; dbSNP:rs121913503; to M: in GLM; somatic mutation; reduces enzymatic activity; dbSNP:rs121913503; to S: found in patients with cartilagenous tumors; dbSNP:rs1057519736; to T: found in patients with cartilagenous tumors; to W: found in patients with cartilagenous tumors; dbSNP:rs1057519906
K413 (= K373) modified: N6-acetyllysine; mutation to A: 44-fold loss in activity.; mutation to Q: 20-fold decrease in Vmax.; mutation to R: No appreciable difference in Km for isocitrate and NADP.

5i96A Crystal structure of human mitochondrial isocitrate dehydrogenase (idh2) r140q mutant homodimer in complex with ag-221 (enasidenib) inhibitor. (see paper)
69% identity, 99% coverage: 3:404/407 of query aligns to 3:410/417 of 5i96A

query
sites
5i96A

K

R

I

I

K

K

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A

A

N

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D

D

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G

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D

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E

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M

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Q

F

F

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I

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K

D

E

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L

L

I

I

L

L

P

P

Y

H

L

V

D

D

V

I

D

Q

L

L

K

K

Y

Y

Y

F

D

D

L

L

S

G

V

L

E

P

N

N

R

R

D

D

K

Q

T

T

D

D

R

Q

V

V

T

T

V

I

E

D

S

S

A

A

N

L

A

A

I

T

K

Q

Q

K

Y

Y

G

S

V

V

G

A

V

V

K

K

C

C

A

A

T
|
T

I

I

T
|
T

P

P

D

D

E

E

A

A

R

R

V

V

T

E

E

E

F

F

N

K

L

L

K

K

M

M

W

W

K

K

S

S

P

P

N

N

G

G

T

T

I

I

R

Q

N

N

I

I

L

L

G

G

T

T

V

V

F

F

R

R

E

E

P

P

I

I

V

I

C

C

S

K

N

N

V

I

P

P

R

R

Y

L

V

V

P

P

G

G

W

W

T

T

K

K

P

P

I

I

I

T

I

I

G

G

R

R

H

H

A

A

F

H

G

G

D

D

Q

Q

Y

Y

K

K

A

A

T

T

D

D

F

F

V

V

V

A

P

D

G

R

K

A

G

G

K

T

L

F

T

K

I

M

K

V

W

F

V

T

P

P

E

K

G

D

G

G

G

S

E

G

P

V

I

K

E

E

Q

W

E

E

V

V

Y

Y

D

N

F

F

P

P

A

A

S

G

G

G

V

V

A

G

M

M

G

G

M

M

Y

Y

N

N

L

T

D

D

E

E

S

S

I

I

E

S

G

G

F

F

A

A

H

H

S

S

S

C

F

F

M

Q

Y

Y

G

A

L

I

E

Q

R

K

G

K

Y

W

P

P

V

L

Y

Y

L

M

S

S

T

T

K

K

N

N

T

T

I

I

L

L

K

K

A

A

Y

Y

D

D

G

G

R

R

F

F

K

K

D

D

I

I

F

F

Q

Q

K

E

V

I

F

F

D

D

E

K

H

H

Y

Y

A

K

A

T

Q

D

F

F

K

D

A

K

K

N

G

K

L

I

V

W

Y

Y

E

E

H

H

R

R

L

L

I

I

D

D

M

M

V

V

A

A

S

Q

A

V

L

L

K

K

W

S

E

S

G

G

F

F

V

V

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

I
|
I

V

L

A

A

Q

Q

G

G

F

F

G

G

S

S

L

L

G

G

L

L

M

M

T

T

S

S

V

V

L

L

I

V

T

C

P

P

D

D

G

G

K

K

T

T

V

I

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

E

E

H

H

Q

Q

K

K

G

G

K

R

E

P

T

T

S

S

T

T

N
|
N

P

P

I

I

A

A

S

S

I

I

Y

F

A

A

W

W

T

T

Q

R

G

G

L

L

A

E

Y

H

R

R

G

G

K

K

F

L

D

D

N

G

T

N

P

Q

D

D

V

L

V

I

K

R

F

F

A

A

E

Q

T

M

L

L

E

E

R

K

V

V

C

C

V

V

E

E

T

T

V

V

E

E

S

S

G

G

F

A

M

M

T

T

K

K

D

D

L

L

A

A

I

G

L

C

I

I

G

H

P

G

-

L

-

S

-

N

-

V

-

K

-

L

D

N

Q

E

P

H

W

F

L

L

T

N

T

T

K

T

Q

D

F

F

L

L

D

D

K

T

L

I

D

K

E

S

N

N

L

L

Q

D

K

R

K

A

M

L

A

G

binding 2-methyl-1-[(4-[6-(trifluoromethyl)pyridin-2-yl]-6-{[2-(trifluoromethyl)pyridin-4-yl]amino}-1,3,5-triazin-2-yl)amino]propan-2-ol: Y271 (= Y271), D272 (= D272), V275 (= V275), Q276 (= Q276), I279 (= I279)
binding calcium ion: D274 (= D274), S277 (= S277)
binding nadph dihydro-nicotinamide-adenine-dinucleotide phosphate: T75 (= T75), T77 (= T77), E305 (= E305), H308 (= H308), G309 (= G309), T310 (= T310), V311 (= V311), T312 (= T312), R313 (= R313), H314 (= H314), N327 (= N327)

5i95A Crystal structure of human mitochondrial isocitrate dehydrogenase r140q mutant homodimer bound to NADPH and alpha-ketoglutaric acid (see paper)
69% identity, 99% coverage: 3:404/407 of query aligns to 3:410/413 of 5i95A

query
sites
5i95A

K

R

I

I

K

K

V

V

A

A

N

K

P

P

V

V

E

E

L

M

D

D

G

G

D

D

E

E

M

M

T

T

R

R

I

I

W

W

Q

Q

F

F

I

I

K

K

D

E

K

K

L

L

I

I

L

L

P

P

Y

H

L

V

D

D

V

I

D

Q

L

L

K

K

Y

Y

Y

F

D

D

L

L

S

G

V

L

E

P

N

N

R

R

D

D

K

Q

T

T

D

D

R

Q

V

V

T

T

V

I

E

D

S

S

A

A

N

L

A

A

I

T

K

Q

Q

K

Y

Y

G

S

V

V

G

A

V

V

K

K

C

C

A

A

T
|
T

I
|
I

T
|
T

P

P

D

D

E

E

A

A

R

R

V

V

T

E

E

E

F

F

N

K

L

L

K

K

M

M

W

W

K

K

S
|
S

P

P

N
|
N

G

G

T

T

I

I

R

Q

N

N

I

I

L

L

G

G

T

T

V

V

F

F

R
|
R

E

E

P

P

I

I

V

I

C

C

S

K

N

N

V

I

P

P

R

R

Y

L

V

V

P

P

G

G

W

W

T

T

K

K

P

P

I

I

I

T

I

I

G

G

R

R

H

H

A

A

F

H

G

G

D

D

Q

Q

Y

Y

K

K

A

A

T

T

D

D

F

F

V

V

V

A

P

D

G

R

K

A

G

G

K

T

L

F

T

K

I

M

K

V

W

F

V

T

P

P

E

K

G

D

G

G

G

S

E

G

P

V

I

K

E

E

Q

W

E

E

V

V

Y

Y

D

N

F

F

P

P

A

A

S

G

G

G

V

V

A

G

M

M

G

G

M

M

Y

Y

N

N

L

T

D

D

E

E

S

S

I

I

E

S

G

G

F

F

A

A

H

H

S

S

S

C

F

F

M

Q

Y

Y

G

A

L

I

E

Q

R

K

G

K

Y

W

P

P

V

L

Y

Y

L

M

S

S

T

T

K

K

N

N

T

T

I

I

L

L

K

K

A

A

Y

Y

D

D

G

G

R

R

F

F

K

K

D

D

I

I

F

F

Q

Q

K

E

V

I

F

F

D

D

E

K

H

H

Y

Y

A

K

A

T

Q

D

F

F

K

D

A

K

K

N

G

K

L

I

V

W

Y

Y

E

E

H

H

R

R

L

L

I

I

D

D

M

M

V

V

A

A

S

Q

A

V

L

L

K

K

W

S

E

S

G

G

F

F

V

V

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

I

I

V

L

A

A

Q

Q

G

G

F

F

G

G

S

S

L

L

G

G

L

L

M

M

T

T

S

S

V

V

L

L

I

V

T

C

P

P

D

D

G

G

K

K

T

T

V

I

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

E

E

H

H

Q

Q

K

K

G

G

K

R

E

P

T

T

S

S

T

T

N
|
N

P

P

I

I

A

A

S

S

I

I

Y

F

A

A

W

W

T

T

Q

R

G

G

L

L

A

E

Y

H

R

R

G

G

K

K

F

L

D

D

N

G

T

N

P

Q

D

D

V

L

V

I

K

R

F

F

A

A

E

Q

T

M

L

L

E

E

R

K

V

V

C

C

V

V

E

E

T

T

V

V

E

E

S

S

G

G

F

A

M

M

T

T

K

K

D

D

L

L

A

A

I

G

L

C

I

I

G

H

P

G

-

L

-

S

-

N

-

V

-

K

-

L

D

N

Q

E

P

H

W

F

L

L

T

N

T

T

K

T

Q

D

F

F

L

L

D

D

K

T

L

I

D

K

E

S

N

N

L

L

Q

D

K

R

K

A

M

L

A

G

binding 2-oxoglutaric acid: T77 (= T77), S94 (= S94), N96 (= N96), R109 (= R109), D274 (= D274)
binding nadph dihydro-nicotinamide-adenine-dinucleotide phosphate: T75 (= T75), I76 (= I76), T77 (= T77), N96 (= N96), H308 (= H308), G309 (= G309), T310 (= T310), V311 (= V311), T312 (= T312), R313 (= R313), H314 (= H314), N327 (= N327)

6adiA Crystal structures of idh2 r140q in complex with ag-881 (see paper)
69% identity, 99% coverage: 3:404/407 of query aligns to 3:410/418 of 6adiA

query
sites
6adiA

K

R

I

I

K

K

V

V

A

A

N

K

P

P

V

V

E

E

L

M

D

D

G

G

D

D

E

E

M

M

T

T

R

R

I

I

W

W

Q

Q

F

F

I

I

K

K

D

E

K

K

L

L

I

I

L

L

P

P

Y

H

L

V

D

D

V

I

D

Q

L

L

K

K

Y

Y

Y

F

D

D

L

L

S

G

V

L

E

P

N

N

R

R

D

D

K

Q

T

T

D

D

R

Q

V

V

T

T

V

I

E

D

S

S

A

A

N

L

A

A

I

T

K

Q

Q

K

Y

Y

G

S

V

V

G

A

V

V

K

K

C

C

A

A

T
|
T

I
|
I

T
|
T

P

P

D

D

E

E

A

A

R

R

V

V

T

E

E

E

F

F

N

K

L

L

K

K

M

M

W

W

K

K

S

S

P

P

N
|
N

G

G

T

T

I

I

R

Q

N

N

I

I

L

L

G

G

T

T

V

V

F

F

R

R

E

E

P

P

I

I

V

I

C

C

S

K

N

N

V

I

P

P

R

R

Y

L

V

V

P

P

G

G

W

W

T

T

K

K

P

P

I

I

I

T

I

I

G

G

R

R

H

H

A

A

F

H

G

G

D

D

Q

Q

Y

Y

K

K

A

A

T

T

D

D

F

F

V

V

V

A

P

D

G

R

K

A

G

G

K

T

L

F

T

K

I

M

K

V

W

F

V

T

P

P

E

K

G

D

G

G

G

S

E

G

P

V

I

K

E

E

Q

W

E

E

V

V

Y

Y

D

N

F

F

P

P

A

A

S

G

G

G

V

V

A

G

M

M

G

G

M

M

Y

Y

N

N

L

T

D

D

E

E

S

S

I

I

E

S

G

G

F

F

A

A

H

H

S

S

S

C

F

F

M

Q

Y

Y

G

A

L

I

E

Q

R

K

G

K

Y

W

P

P

V

L

Y

Y

L

M

S

S

T

T

K

K

N

N

T

T

I

I

L

L

K

K

A

A

Y

Y

D

D

G

G

R

R

F

F

K

K

D

D

I

I

F

F

Q

Q

K

E

V

I

F

F

D

D

E

K

H

H

Y

Y

A

K

A

T

Q

D

F

F

K

D

A

K

K

N

G

K

L

I

V

W

Y

Y

E

E

H

H

R

R

L

L

I

I

D

D

M

M

V
|
V

A

A

S

Q

A
x
V

L

L

K

K

W

S

E

S

G

G

F

F

V

V

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

I
|
I

V

L

A

A

Q

Q

G

G

F

F

G

G

S

S

L

L

G

G

L

L

M

M

T

T

S

S

V

V

L

L

I

V

T

C

P

P

D

D

G

G

K

K

T

T

V

I

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

E

E

H

H

Q

Q

K

K

G

G

K

R

E

P

T

T

S

S

T
|
T

N
|
N

P

P

I

I

A

A

S

S

I

I

Y

F

A

A

W

W

T

T

Q

R

G

G

L

L

A

E

Y

H

R

R

G

G

K

K

F

L

D

D

N

G

T

N

P

Q

D

D

V

L

V

I

K

R

F

F

A

A

E

Q

T

M

L

L

E

E

R

K

V

V

C

C

V

V

E

E

T

T

V

V

E

E

S

S

G

G

F

A

M

M

T

T

K

K

D

D

L

L

A

A

I

G

L

C

I

I

G

H

P

G

-

L

-

S

-

N

-

V

-

K

-

L

D

N

Q

E

P

H

W

F

L

L

T

N

T

T

K

T

Q

D

F

F

L

L

D

D

K

T

L

I

D

K

E

S

N

N

L

L

Q

D

K

R

K

A

M

L

A

G

binding 6-(6-chloropyridin-2-yl)-N2,N4-bis[(2R)-1,1,1-trifluoropropan-2-yl]-1,3,5-triazine-2,4-diamine: V254 (= V254), V257 (≠ A257), D272 (= D272), V275 (= V275), Q276 (= Q276), I279 (= I279)
binding nadph dihydro-nicotinamide-adenine-dinucleotide phosphate: T75 (= T75), I76 (= I76), T77 (= T77), N96 (= N96), E305 (= E305), H308 (= H308), G309 (= G309), T310 (= T310), V311 (= V311), H314 (= H314), T326 (= T326), N327 (= N327)

4ja8A Complex of mitochondrial isocitrate dehydrogenase r140q mutant with agi-6780 inhibitor (see paper)
69% identity, 99% coverage: 3:404/407 of query aligns to 3:410/416 of 4ja8A

query
sites
4ja8A

K

R

I

I

K

K

V

V

A

A

N

K

P

P

V

V

E

E

L

M

D

D

G

G

D

D

E

E

M

M

T

T

R

R

I

I

W

W

Q

Q

F

F

I

I

K

K

D

E

K

K

L

L

I

I

L

L

P

P

Y

H

L

V

D

D

V

I

D

Q

L

L

K

K

Y

Y

Y

F

D

D

L

L

S

G

V

L

E

P

N

N

R

R

D

D

K

Q

T

T

D

D

R

Q

V

V

T

T

V

I

E

D

S

S

A

A

N

L

A

A

I

T

K

Q

Q

K

Y

Y

G

S

V

V

G

A

V

V

K

K

C

C

A

A

T
|
T

I

I

T
|
T

P

P

D

D

E

E

A

A

R

R

V

V

T

E

E

E

F

F

N

K

L

L

K

K

M

M

W

W

K

K

S

S

P

P

N
|
N

G

G

T

T

I

I

R

Q

N

N

I

I

L

L

G

G

T

T

V

V

F

F

R

R

E

E

P

P

I

I

V

I

C

C

S

K

N

N

V

I

P

P

R

R

Y

L

V

V

P

P

G

G

W
|
W

T

T

K

K

P

P

I

I

I

T

I

I

G

G

R

R

H

H

A

A

F

H

G

G

D

D

Q

Q

Y

Y

K

K

A

A

T

T

D

D

F

F

V

V

V

A

P

D

G

R

K

A

G

G

K

T

L

F

T

K

I

M

K

V

W

F

V

T

P

P

E

K

G

D

G

G

G

S

E

G

P

V

I

K

E

E

Q

W

E

E

V

V

Y

Y

D

N

F

F

P

P

A

A

S

G

G

G

V

V

A

G

M

M

G

G

M

M

Y

Y

N

N

L

T

D

D

E

E

S

S

I

I

E

S

G

G

F

F

A

A

H

H

S

S

S

C

F

F

M

Q

Y

Y

G

A

L

I

E

Q

R

K

G

K

Y

W

P

P

V

L

Y

Y

L

M

S

S

T

T

K

K

N

N

T

T

I

I

L

L

K

K

A

A

Y

Y

D

D

G

G

R

R

F

F

K

K

D

D

I

I

F

F

Q

Q

K

E

V

I

F

F

D

D

E

K

H

H

Y

Y

A

K

A

T

Q

D

F

F

K

D

A

K

K

N

G

K

L

I

V

W

Y

Y

E

E

H

H

R

R

L

L

I

I

D

D

M

M

V

V

A

A

S

Q

A
x
V

L

L

K

K

W

S

E

S

G

G

F

F

V

V

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

I
|
I

V

L

A

A

Q

Q

G

G

F

F

G

G

S

S

L

L

G

G

L

L

M

M

T

T

S

S

V

V

L

L

I

V

T

C

P

P

D

D

G

G

K

K

T

T

V

I

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

E

E

H

H

Q

Q

K

K

G

G

K

R

E

P

T

T

S

S

T

T

N
|
N

P

P

I

I

A

A

S

S

I

I

Y

F

A

A

W

W

T

T

Q

R

G

G

L

L

A

E

Y

H

R

R

G

G

K

K

F

L

D

D

N

G

T

N

P

Q

D

D

V

L

V

I

K

R

F

F

A

A

E

Q

T

M

L

L

E

E

R

K

V

V

C

C

V

V

E

E

T

T

V

V

E

E

S

S

G

G

F

A

M

M

T

T

K

K

D

D

L

L

A

A

I

G

L

C

I

I

G

H

P

G

-

L

-

S

-

N

-

V

-

K

-

L

D

N

Q

E

P

H

W

F

L

L

T

N

T

T

K

T

Q

D

F

F

L

L

D

D

K

T

L

I

D

K

E

S

N

N

L

L

Q

D

K

R

K

A

M

L

A

G

binding 1-[5-(cyclopropylsulfamoyl)-2-thiophen-3-yl-phenyl]-3-[3-(trifluoromethyl)phenyl]urea: W124 (= W124), V257 (≠ A257), Y271 (= Y271), D272 (= D272), V275 (= V275), Q276 (= Q276), I279 (= I279)
binding calcium ion: D274 (= D274), D278 (= D278)
binding nadph dihydro-nicotinamide-adenine-dinucleotide phosphate: T75 (= T75), T77 (= T77), N96 (= N96), H308 (= H308), G309 (= G309), T310 (= T310), V311 (= V311), T312 (= T312), R313 (= R313), H314 (= H314), N327 (= N327)

5svoA Structure of idh2 mutant r140q (see paper)
69% identity, 99% coverage: 3:404/407 of query aligns to 2:409/410 of 5svoA

query
sites
5svoA

K

R

I

I

K

K

V

V

A

A

N

K

P

P

V

V

E

E

L

M

D

D

G

G

D

D

E

E

M

M

T

T

R

R

I

I

W

W

Q

Q

F

F

I

I

K

K

D

E

K

K

L

L

I

I

L

L

P

P

Y

H

L

V

D

D

V

I

D

Q

L

L

K

K

Y

Y

Y

F

D

D

L

L

S

G

V

L

E

P

N

N

R

R

D

D

K

Q

T

T

D

D

R

Q

V

V

T

T

V

I

E

D

S

S

A

A

N

L

A

A

I

T

K

Q

Q

K

Y

Y

G

S

V

V

G

A

V

V

K

K

C

C

A

A

T
|
T

I

I

T
|
T

P

P

D

D

E

E

A

A

R

R

V

V

T

E

E

E

F

F

N

K

L

L

K

K

M

M

W

W

K

K

S

S

P

P

N

N

G

G

T

T

I

I

R

Q

N

N

I

I

L

L

G

G

T

T

V

V

F

F

R

R

E

E

P

P

I

I

V

I

C

C

S

K

N

N

V

I

P

P

R

R

Y

L

V

V

P

P

G

G

W

W

T

T

K

K

P

P

I

I

I

T

I

I

G

G

R

R

H

H

A

A

F

H

G

G

D

D

Q

Q

Y

Y

K

K

A

A

T

T

D

D

F

F

V

V

V

A

P

D

G

R

K

A

G

G

K

T

L

F

T

K

I

M

K

V

W

F

V

T

P

P

E

K

G

D

G

G

G

S

E

G

P

V

I

K

E

E

Q

W

E

E

V

V

Y

Y

D

N

F

F

P

P

A

A

S

G

G

G

V

V

A

G

M

M

G

G

M

M

Y

Y

N

N

L

T

D

D

E

E

S

S

I

I

E

S

G

G

F

F

A

A

H

H

S

S

S

C

F

F

M

Q

Y

Y

G

A

L

I

E

Q

R

K

G

K

Y

W

P

P

V

L

Y

Y

L

M

S

S

T

T

K

K

N

N

T

T

I

I

L

L

K

K

A

A

Y

Y

D

D

G

G

R

R

F

F

K

K

D

D

I

I

F

F

Q

Q

K

E

V

I

F

F

D

D

E

K

H

H

Y

Y

A

K

A

T

Q

D

F

F

K

D

A

K

K

N

G

K

L

I

V

W

Y

Y

E

E

H

H

R

R

L

L

I

I

D

D

M

M

V

V

A

A

S

Q

A

V

L

L

K

K

W

S

E

S

G

G

F

F

V

V

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

I

I

V

L

A

A

Q

Q

G

G

F

F

G

G

S

S

L

L

G

G

L

L

M

M

T

T

S

S

V

V

L

L

I

V

T

C

P

P

D

D

G

G

K

K

T

T

V

I

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

E

E

H

H

Q

Q

K

K

G

G

K

R

E

P

T

T

S

S

T
|
T

N
|
N

P

P

I

I

A

A

S

S

I

I

Y

F

A

A

W

W

T

T

Q

R

G

G

L

L

A

E

Y

H

R

R

G

G

K

K

F

L

D

D

N

G

T

N

P

Q

D

D

V

L

V

I

K

R

F

F

A

A

E

Q

T

M

L

L

E

E

R

K

V

V

C

C

V

V

E

E

T

T

V

V

E

E

S

S

G

G

F

A

M

M

T

T

K

K

D

D

L

L

A

A

I

G

L

C

I

I

G

H

P

G

-

L

-

S

-

N

-

V

-

K

-

L

D

N

Q

E

P

H

W

F

L

L

T

N

T

T

K

T

Q

D

F

F

L

L

D

D

K

T

L

I

D

K

E

S

N

N

L

L

Q

D

K

R

K

A

M

L

A

G

binding nadp nicotinamide-adenine-dinucleotide phosphate: T74 (= T75), T76 (= T77), H307 (= H308), G308 (= G309), T309 (= T310), V310 (= V311), T311 (= T312), R312 (= R313), H313 (= H314), T325 (= T326), N326 (= N327)

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)
67% identity, 99% coverage: 1:404/407 of query aligns to 1:410/414 of O88844

query
sites
O88844

M

M

T

S

K

R

I

K

K

I

V

Q

A

G

N

G

P

S

V

V

E

E

L

M

D

Q

G

G

D

D

E

E

M

M

T

T

R

R

I

I

W

W

Q

E

F

L

I

I

K

K

D

E

K

K

L

L

I

I

L

L

P

P

Y

Y

L

V

D

E

V

L

D

D

L

L

K

H

Y

S

Y

Y

D

D

L

L

S

G

V

I

E

E

N

N

R

R

D

D

K

A

T

T

D

N

D

D

R

Q

V

V

T

T

V

K

E

D

S

A

A

A

N

E

A

A

I

I

K

K

Q

K

Y

Y

G

N

V

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

T

E

E

E

F

F

N

K

L

L

K

K

K

Q

M

M

W

W

K

K

S
|
S

P
|
P

N
|
N

G
|
G

T
|
T

I
|
I

R
|
R

N

N

I

I

L

L

G

G

T

T

V

V

F

F

R
|
R

E

E

P

A

I

I

V

I

C

C

S

K

N

N

V

I

P

P

R

R

Y

L

V

V

P

T

G

G

W

W

T

V

K

K

P

P

I

I

G

G

R
|
R

H

H

A

A

F

Y

G

G

D

D

Q

Q

Y

Y

K

R

A

A

T

T

D

D

F

F

V

V

P

P

G

G

K

P

G

G

K

K

L

V

T

E

I

I

K

T

W

Y

V

T

P

P

E

K

G

D

G

G

G

T

E

Q

P

K

I

V

E

T

Q

Y

E

M

V

V

Y

H

D

D

F

F

P

E

-

E

A

G

S

G

G

G

V

V

A

A

M

M

G

G

M

M

Y

Y

N

N

L

Q

D

D

E

K

S

S

I

I

E

E

G

D

F

F

A

A

H

H

S

S

F

F

M

Q

Y

M

G

A

L

L

E

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

R

R

F

F

K

K

D

D

I

I

F

F

Q

Q

K

E

V

I

F

Y

D

D

E

K

H

K

Y

Y

A

K

A

S

Q

Q

F

F

K

E

A

A

K

Q

G

K

L

I

V
x
C

Y

Y

E

E

H

H

R

R

L

L

I

I

D

D

M

M

V

V

A

A

S

Q

A

A

L

M

K
|
K

W

S

E

E

G

G

F

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

I

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

I

I

T

C

P

P

D

D

G

G

K

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

E

M

H

Y

Q

Q

K

K

G

G

K

Q

E

E

T

T

S

S

T

T

N
|
N

P

P

I

I

A

A

S

S

I

I

Y

F

A

A

W

W

T

S

Q

R

G

G

L

L

A

A

Y

H

R

R

G

A

K

K

F

L

D

D

N

N

T

N

P

T

D

E

V

L

V

S

K

F

F

F

A

A

E

K

T

A

L

L

E

E

R

D

V

V

C

C

V

I

E

E

T

T

V

I

E

E

S

A

G

G

F

F

M

M

T

T

K

K

D

D

L

L

A

A

I

A

L
x
C

I

I

G

K

-

G

-

L

P

P

D

N

-

V

-

Q

-

R

Q

S

P

D

W

Y

L

L

T

N

T

T

K

F

Q

E

F

F

L

M

D

D

K

K

L

L

D

G

E

E

N

N

L

L

Q

K

K

A

K

K

M

L

A

A

TIT 75:77 (= TIT 75:77) binding
T77 (= T77) binding in other chain
R82 (= R82) binding
94:100 (vs. 94:100, 100% identical) binding in other chain
R109 (= R109) binding in other chain
R132 (= R132) binding in other chain
K212 (= K211) binding
C245 (≠ V244) mutation to S: No effect on inhibition by cadmium ions.
K260 (= K259) binding
GTVTRH 310:315 (= GTVTRH 309:314) binding
N328 (= N327) binding
C379 (≠ L378) mutation to S: Decreased inhibition by cadmium ions.

5yziA Crystal structure of mouse cytosolic isocitrate dehydrogenase complexed with cadmium (see paper)
69% identity, 97% coverage: 10:404/407 of query aligns to 7:407/409 of 5yziA

query
sites
5yziA

V

V

E

E

L

M

D

Q

G

G

D

D

E

E

M

M

T

T

R

R

I

I

W

W

Q

E

F

L

I

I

K

K

D

E

K

K

L

L

I

I

L

L

P

P

Y

Y

L

V

D

E

V

L

D

D

L

L

K

H

Y

S

Y

Y

D

D

L

L

S

G

V

I

E

E

N

N

R

R

D

D

K

A

T

T

D

N

D

D

R

Q

V

V

T

T

V

K

E

D

S

A

A

A

N

E

A

A

I

I

K

K

Q

K

Y

Y

G

N

V

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

T

E

E

E

F

F

N

K

L

L

K

K

K

Q

M

M

W

W

K

K

S

S

P

P

N
|
N

G

G

T

T

I

I

R

R

N

N

I

I

L

L

G

G

T

T

V

V

F

F

R

R

E

E

P

A

I

I

V

I

C

C

S

K

N

N

V

I

P

P

R

R

Y

L

V

V

P

T

G

G

W

W

T

V

K

K

P

P

I

I

G

G

R

R

H

H

A

A

F

Y

G

G

D

D

Q

Q

Y

Y

K

R

A

A

T

T

D

D

F

F

V

V

P

P

G

G

K

P

G

G

K

K

L

V

T

E

I

I

K

T

W

Y

V

T

P

P

E

K

G

D

G

G

G

T

E

Q

P

K

I

V

E

T

Q

Y

E

M

V

V

Y

H

D

D

F

F

P

E

-

E

A

G

S

G

G

G

V

V

A

A

M

M

G

G

M

M

Y

Y

N

N

L

Q

D

D

E

K

S

S

I

I

E

E

G

D

F

F

A

A

H

H

S

S

F

F

M

Q

Y

M

G

A

L

L

E

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

R

R

F

F

K

K

D

D

I

I

F

F

Q

Q

K

E

V

I

F

Y

D

D

E

K

H

K

Y

Y

A

K

A

S

Q

Q

F

F

K

E

A

A

K

Q

G

K

L

I

V

C

Y

Y

E

E

H

H

R

R

L

L

I

I

D

D

M

M

V

V

A

A

S

Q

A

A

L

M

K

K

W

S

E

E

G

G

F

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

I

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

I

I

T

C

P

P

D

D

G

G

K

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

E

M

H

Y

Q

Q

K

K

G

G

K

Q

E

E

T

T

S

S

T
|
T

N
|
N

P

P

I

I

A

A

S

S

I

I

Y

F

A

A

W

W

T

S

Q

R

G

G

L

L

A

A

Y

H

R

R

G

A

K

K

F

L

D

D

N

N

T

N

P

T

D

E

V

L

V

S

K

F

F

F

A

A

E

K

T

A

L

L

E

E

R

D

V

V

C

C

V

I

E

E

T

T

V

I

E

E

S

A

G

G

F

F

M

M

T

T

K

K

D

D

L

L

A

A

I

A

L

C

I

I

G

K

-

G

-

L

P

P

D

N

-

V

-

Q

-

R

Q

S

P

D

W

Y

L

L

T

N

T

T

K

F

Q

E

F

F

L

M

D

D

K

K

L

L

D

G

E

E

N

N

L

L

Q

K

K

A

K

K

M

L

A

A

binding cadmium ion: D272 (= D274), D276 (= D278)
binding nadp nicotinamide-adenine-dinucleotide phosphate: T72 (= T75), T74 (= T77), N93 (= N96), H306 (= H308), G307 (= G309), T308 (= T310), V309 (= V311), T310 (= T312), R311 (= R313), H312 (= H314), T324 (= T326), N325 (= N327)

6ajcA Crystal structure of trypanosoma cruzi cytosolic isocitrate dehydrogenase in complex with NADP+, isocitrate and ca2+
68% identity, 98% coverage: 3:401/407 of query aligns to 3:406/413 of 6ajcA

query
sites
6ajcA

K

K

I

I

K

K

V

V

A

A

N

G

P

T

V

V

E

E

L

L

D

D

G

G

D

D

E

E

M

M

T

T

R

R

I

V

I

I

W

W

Q

K

F

M

I

I

K

K

D

E

K

E

L

L

I

I

L

F

P

P

Y

F

L

L

D

D

V

V

D

P

L

I

K

E

Y

Y

D

D

L

L

S

G

V

M

E

E

N

N

R

R

D

D

K

K

T

T

D

D

R

Q

V

V

T

T

V

V

E

D

S

A

A

A

N

H

A

A

I

I

K

K

Q

K

Y

H

G

G

V

V

G

G

V

V

K

K

C

C

A

A

T
|
T

I
|
I

T
|
T

P

P

D

D

E

E

A

A

R

R

V

V

T

R

E

E

F

F

N

N

L

L

K

K

K

Q

M

M

W

W

K

K

S

S

P

P

N
|
N

G

G

T

T

I

I

R

R

N

N

I

I

L

L

G

G

T

T

V

V

F

F

R

R

E

E

P

P

I

I

V

M

C

C

S

K

N

N

V

V

P

P

R

R

Y

L

V

V

P

T

G

T

W

W

T

K

K

H

P

P

I

I

I

V

I

I

G

G

R

R

H

H

A

A

F

F

G

G

D

D

Q

Q

Y

Y

K

R

A

A

T

T

D

D

F

L

V

V

P

N

G

G

K

P

G

G

K

T

L

F

T

E

I

I

K

H

W

F

V

V

P

P

E

E

G

S

G

G

E

A

P

A

I

Q

E

V

Q

Q

E

K

V

V

Y

F

D

D

F

F

P

K

A

S

S

G

G

G

V

V

A

L

M

M

G

G

M

M

Y

Y

N

N

L

T

D

D

E

E

S

S

I

I

E

K

G

D

F

F

A

A

H

K

S

S

S

C

F

F

M

E

Y

Y

G

A

L

L

E

S

R

K

G

K

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

R

Y

Y

D

D

G

G

R

R

F

F

K

K

D

D

I

I

F

F

Q

A

K

E

V

M

F

Y

D

K

E

A

H

S

Y

Y

A

E

A

A

Q

D

F

Y

K

K

A

K

K

A

G

G

L

I

V

W

Y

Y

E

E

H

H

R

R

L

L

I

I

D

D

D
|
D

M

M

V

V

A

A

S

Y

A

A

L

M

K
|
K

W

S

E

E

G

G

F

Y

V

V

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

I

S

V

V

A

A

Q

Q

G

G

F

F

G

G

S

S

L
|
L

G

G

L

L

M

M

T

T

S

S

V

V

L

L

I

M

T

S

P

P

D

D

G

G

K

R

T

T

V

V

E

E

A

A

E

E

A

A

A
|
A

H
|
H

G
|
G

T
|
T

V
|
V

T

T

R
|
R

H
|
H

Y

Y

R

R

E

Q

H

H

Q

Q

K

K

G

G

K

E

E

E

T

T

S

S

T

T

N
|
N

P

P

I

V

A

A

S

S

I

I

Y

F

A

A

W

W

T

T

Q

R

G

G

L

L

A

M

Y

H

R

R

G

G

K

K

F

L

D

D

N

Q

T

N

P

E

D

K

V

L

V

V

K

Q

F

F

A

S

E

M

T

L

L

L

E

E

R

K

V

V

C

V

V

V

E

S

T

T

V

I

E

E

S

A

G

G

F

F

M

M

T

T

K

K

D

D

L

L

A

A

I

I

L

C

I

I

G

K

-

G

-

M

-

N

-

H

-

V

P

T

D

R

Q

S

P

D

W

Y

L

L

T

N

T

T

K

Q

Q

E

F

F

L

I

D

H

K

K

L

L

D

A

E

D

N

E

L

M

Q

R

K

K

binding calcium ion: D274 (= D274), D278 (= D278)
binding nadp nicotinamide-adenine-dinucleotide phosphate: T75 (= T75), I76 (= I76), T77 (= T77), N96 (= N96), D252 (= D252), K259 (= K259), L287 (= L287), A307 (= A307), H308 (= H308), G309 (= G309), T310 (= T310), V311 (= V311), R313 (= R313), H314 (= H314), N327 (= N327)

1t0lA Crystal structure of human cytosolic NADP(+)-dependent isocitrate dehydrogenase in complex with NADP, isocitrate, and calcium(2+) (see paper)
67% identity, 99% coverage: 1:404/407 of query aligns to 1:410/414 of 1t0lA

query
sites
1t0lA

M

M

T

S

K

K

I

K

K

I

V

S

A

G

N

G

P

S

V

V

E

E

L

M

D

Q

G

G

D

D

E

E

M

M

T

T

R

R

I

I

W

W

Q

E

F

L

I

I

K

K

D

E

K

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

S

G

V

I

E

E

N

N

R

R

D

D

K

A

T

T

D

N

D

D

R

Q

V

V

T

T

V

K

E

D

S

A

A

A

N

E

A

A

I

I

K

K

Q

K

Y

H

G

N

V

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

T

E

E

E

F

F

N

K

L

L

K

K

K

Q

M

M

W

W

K

K

S

S

P

P

N
|
N

G

G

T

T

I

I

R

R

N

N

I

I

L

L

G

G

T

T

V

V

F

F

R

R

E

E

P

A

I

I

V

I

C

C

S

K

N

N

V

I

P

P

R

R

Y

L

V

V

P

S

G

G

W

W

T

V

K

K

P

P

I

I

G

G

R

R

H

H

A

A

F

Y

G

G

D

D

Q

Q

Y

Y

K

R

A

A

T

T

D

D

F

F

V

V

P

P

G

G

K

P

G

G

K

K

L

V

T

E

I

I

K

T

W

Y

V

T

P

P

E

S

G

D

G

G

G

T

E

Q

P

K

I

V

E

T

Q

Y

E

L

V

V

Y

H

D

N

F

F

P

E

-

E

A

G

S

G

G

G

V

V

A

A

M

M

G

G

M

M

Y

Y

N

N

L

Q

D

D

E

K

S

S

I

I

E

E

G

D

F

F

A

A

H

H

S

S

F

F

M

Q

Y

M

G

A

L

L

E

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

R

R

F

F

K

K

D

D

I

I

F

F

Q

Q

K

E

V

I

F

Y

D

D

E

K

H

Q

Y

Y

A

K

A

S

Q

Q

F

F

K

E

A

A

K

Q

G

K

L

I

V

W

Y

Y

E

E

H

H

R

R

L

L

I

I

D

D

D
|
D

M

M

V

V

A

A

S

Q

A

A

L

M

K
|
K

W

S

E

E

G

G

F

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

I

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

I

V

T

C

P

P

D

D

G

G

K

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

E

M

H

Y

Q

Q

K

K

G

G

K

Q

E

E

T

T

S

S

T
|
T

N
|
N

P

P

I

I

A

A

S

S

I

I

Y

F

A

A

W

W

T

T

Q

R

G

G

L

L

A

A

Y

H

R

R

G

A

K

K

F

L

D

D

N

N

T

N

P

K

D

E

V

L

V

A

K

F

F

F

A

A

E

N

T

A

L

L

E

E

R

E

V

V

C

S

V

I

E

E

T

T

V

I

E

E

S

A

G

G

F

F

M

M

T

T

K

K

D

D

L

L

A

A

I

A

L

C

I

I

G

K

-

G

-

L

P

P

D

N

-

V

-

Q

-

R

Q

S

P

D

W

Y

L

L

T

N

T

T

K

F

Q

E

F

F

L

M

D

D

K

K

L

L

D

G

E

E

N

N

L

L

Q

K

K

I

K

K

M

L

A

A

binding calcium ion: D275 (= D274), D279 (= D278)
binding nadp nicotinamide-adenine-dinucleotide phosphate: A74 (= A74), T75 (= T75), T77 (= T77), N96 (= N96), D253 (= D252), K260 (= K259), L288 (= L287), H309 (= H308), G310 (= G309), T311 (= T310), V312 (= V311), T313 (= T312), R314 (= R313), H315 (= H314), T327 (= T326), N328 (= N327)

1t09A Crystal structure of human cytosolic NADP(+)-dependent isocitrate dehydrogenase in complex NADP (see paper)
67% identity, 99% coverage: 1:404/407 of query aligns to 1:410/414 of 1t09A

query
sites
1t09A

M

M

T

S

K

K

I

K

K

I

V

S

A

G

N

G

P

S

V

V

E

E

L

M

D

Q

G

G

D

D

E

E

M

M

T

T

R

R

I

I

W

W

Q

E

F

L

I

I

K

K

D

E

K

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

S

G

V

I

E

E

N

N

R

R

D

D

K

A

T

T

D

N

D

D

R

Q

V

V

T

T

V

K

E

D

S

A

A

A

N

E

A

A

I

I

K

K

Q

K

Y

H

G

N

V

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

T

E

E

E

F

F

N

K

L

L

K

K

K

Q

M

M

W

W

K

K

S

S

P

P

N
|
N

G

G

T

T

I

I

R

R

N

N

I

I

L

L

G

G

T

T

V

V

F

F

R

R

E

E

P

A

I

I

V

I

C

C

S

K

N

N

V

I

P

P

R

R

Y

L

V

V

P

S

G

G

W

W

T

V

K

K

P

P

I

I

G

G

R

R

H

H

A

A

F

Y

G

G

D

D

Q

Q

Y

Y

K

R

A

A

T

T

D

D

F

F

V

V

P

P

G

G

K

P

G

G

K

K

L

V

T

E

I

I

K

T

W

Y

V

T

P

P

E

S

G

D

G

G

G

T

E

Q

P

K

I

V

E

T

Q

Y

E

L

V

V

Y

H

D

N

F

F

P

E

-

E

A

G

S

G

G

G

V

V

A

A

M

M

G

G

M

M

Y

Y

N

N

L

Q

D

D

E

K

S

S

I

I

E

E

G

D

F

F

A

A

H

H

S

S

F

F

M

Q

Y

M

G

A

L

L

E

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

R

R

F

F

K

K

D

D

I

I

F

F

Q

Q

K

E

V

I

F

Y

D

D

E

K

H

Q

Y

Y

A

K

A

S

Q

Q

F

F

K

E

A

A

K

Q

G

K

L

I

V

W

Y

Y

E

E

H

H

R

R

L

L

I

I

D

D

M

M

V

V

A

A

S

Q

A

A

L

M

K

K

W

S

E

E

G

G

F

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

I
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

I

V

T

C

P

P

D

D

G

G

K

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

E

M

H

Y

Q

Q

K

K

G

G

K

Q

E

E

T

T

S

S

T
|
T

N
|
N

P

P

I

I

A

A

S

S

I

I

Y

F

A

A

W

W

T

T

Q

R

G

G

L

L

A

A

Y

H

R

R

G

A

K

K

F

L

D

D

N

N

T

N

P

K

D

E

V

L

V

A

K

F

F

F

A

A

E

N

T

A

L

L

E

E

R

E

V

V

C

S

V

I

E

E

T

T

V

I

E

E

S

A

G

G

F

F

M

M

T

T

K

K

D

D

L

L

A

A

I

A

L

C

I

I

G

K

-

G

-

L

P

P

D

N

-

V

-

Q

-

R

Q

S

P

D

W

Y

L

L

T

N

T

T

K

F

Q

E

F

F

L

M

D

D

K

K

L

L

D

G

E

E

N

N

L

L

Q

K

K

I

K

K

M

L

A

A

binding nadp nicotinamide-adenine-dinucleotide phosphate: A74 (= A74), T75 (= T75), I76 (= I76), T77 (= T77), R82 (= R82), N96 (= N96), D279 (= D278), S280 (≠ I279), H309 (= H308), G310 (= G309), V312 (= V311), R314 (= R313), T327 (= T326), N328 (= N327)

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, 99% coverage: 1:404/407 of query aligns to 1:410/414 of O75874

query
sites
O75874

M

M

T

S

K

K

I

K

K

I

V

S

A

G

N

G

P

S

V

V

E

E

L

M

D

Q

G

G

D

D

E

E

M

M

T

T

R

R

I

I

W

W

Q

E

F

L

I

I

K

K

D

E

K

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

S

G

V

I

E

E

N

N

R

R

D

D

K

A

T

T

D

N

D

D

R

Q

V

V

T

T

V

K

E

D

S

A

A

A

N

E

A

A

I

I

K

K

Q

K

Y

H

G

N

V

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

T

E

E

E

F

F

N

K

L

L

K

K

K

Q

M

M

W

W

K

K

S
|
S

P
|
P

N
|
N

G
|
G

T
|
T

I
|
I

R
|
R

N

N

I

I

L

L

G

G

T

T

V

V

F

F

R
|
R

E

E

P

A

I

I

V

I

C

C

S

K

N

N

V

I

P

P

R

R

Y

L

V

V

P

S

G

G

W

W

T

V

K

K

P

P

I

I

G

G

R
|
R

H

H

A

A

F

Y

G

G

D

D

Q

Q

Y

Y

K

R

A

A

T

T

D

D

F

F

V

V

P

P

G

G

K

P

G

G

K

K

L

V

T

E

I

I

K

T

W

Y

V

T

P

P

E

S

G

D

G

G

G

T

E

Q

P

K

I

V

E

T

Q

Y

E

L

V

V

Y

H

D

N

F

F

P

E

-

E

A

G

S

G

G

G

V

V

A

A

M

M

G

G

M

M

Y

Y

N

N

L

Q

D

D

E

K

S

S

I

I

E

E

G

D

F

F

A

A

H

H

S

S

F

F

M

Q

Y

M

G

A

L

L

E

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

R

R

F

F

K

K

D

D

I

I

F

F

Q

Q

K

E

V

I

F

Y

D

D

E

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H

Q

Y

Y

A

K

A

S

Q

Q

F

F

K

E

A

A

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Q

G

K

L

I

V

W

Y

Y

E

E

H

H

R

R

L

L

I

I

D

D

M

M

V

V

A

A

S

Q

A

A

L

M

K
|
K

W

S

E

E

G

G

F

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

I

S

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V

A

A

Q

Q

G

G

F

Y

G

G

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S

L

L

G

G

L

M

M

M

T

T

S

S

V

V

L

L

I

V

T

C

P

P

D

D

G

G

K

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

E

M

H

Y

Q

Q

K

K

G

G

K

Q

E

E

T

T

S

S

T

T

N
|
N

P

P

I

I

A

A

S

S

I

I

Y

F

A

A

W

W

T

T

Q

R

G

G

L

L

A

A

Y

H

R

R

G

A

K

K

F

L

D

D

N

N

T

N

P

K

D

E

V

L

V

A

K

F

F

F

A

A

E

N

T

A

L

L

E

E

R

E

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V

C

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V

I

E

E

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I

E

E

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A

G

G

F

F

M

M

T

T

K

K

D

D

L

L

A

A

I

A

L

C

I

I

G

K

-

G

-

L

P

P

D

N

-

V

-

Q

-

R

Q

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P

D

W

Y

L

L

T

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T

T

K

F

Q

E

F

F

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M

D

D

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L

D

G

E

E

N

N

L

L

Q

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I

K

K

M

L

A

A

TIT 75:77 (= TIT 75:77) binding
T77 (= T77) binding in other chain
R82 (= R82) binding
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 (= K211) binding
K260 (= K259) binding
GTVTRH 310:315 (= GTVTRH 309:314) binding
N328 (= N327) binding

5yfnA Human isocitrate dehydrogenase 1 bound with isocitrate
67% identity, 99% coverage: 1:404/407 of query aligns to 8:417/418 of 5yfnA

query
sites
5yfnA

M

M

T

S

K

K

I

K

K

I

V

S

A

G

N

G

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S

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V

E

E

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G

D

D

E

E

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M

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R

I

I

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Q

E

F

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I

I

K

K

D

E

K

K

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L

I

I

L

F

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P

Y

Y

L

V

D

E

V

L

D

D

L

L

K

H

Y

S

Y

Y

D

D

L

L

S

G

V

I

E

E

N

N

R

R

D

D

K

A

T

T

D

N

D

D

R

Q

V

V

T

T

V

K

E

D

S

A

A

A

N

E

A

A

I

I

K

K

Q

K

Y

H

G

N

V

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

T

E

E

E

F

F

N

K

L

L

K

K

K

Q

M

M

W

W

K

K

S

S

P

P

N

N

G

G

T

T

I

I

R

R

N

N

I

I

L

L

G

G

T

T

V

V

F

F

R

R

E

E

P

A

I

I

V

I

C

C

S

K

N

N

V

I

P

P

R

R

Y

L

V

V

P

S

G

G

W

W

T

V

K

K

P

P

I

I

G

G

R

R

H

H

A

A

F

Y

G

G

D

D

Q

Q

Y

Y

K

R

A

A

T

T

D

D

F

F

V

V

P

P

G

G

K

P

G

G

K

K

L

V

T

E

I

I

K

T

W

Y

V

T

P

P

E

S

G

D

G

G

G

T

E

Q

P

K

I

V

E

T

Q

Y

E

L

V

V

Y

H

D

N

F

F

P

E

-

E

A

G

S

G

G

G

V

V

A

A

M

M

G

G

M

M

Y

Y

N

N

L

Q

D

D

E

K

S

S

I

I

E

E

G

D

F

F

A

A

H

H

S

S

F

F

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Q

Y

M

G

A

L

L

E

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

R

R

F

F

K

K

D

D

I

I

F

F

Q

Q

K

E

V

I

F

Y

D

D

E

K

H

Q

Y

Y

A

K

A

S

Q

Q

F

F

K

E

A

A

K

Q

G

K

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I

V

W

Y

Y

E

E

H

H

R

R

L

L

I

I

D

D

M

M

V

V

A

A

S

Q

A

A

L

M

K

K

W

S

E

E

G

G

F

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

I

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

I

V

T

C

P

P

D

D

G

G

K

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

E

M

H

Y

Q

Q

K

K

G

G

K

Q

E

E

T

T

S

S

T

T

N

N

P

P

I

I

A

A

S

S

I

I

Y

F

A

A

W

W

T

T

Q

R

G

G

L

L

A

A

Y

H

R

R

G

A

K

K

F

L

D

D

N

N

T

N

P

K

D

E

V

L

V

A

K

F

F

F

A

A

E

N

T

A

L

L

E

E

R

E

V

V

C

S

V

I

E

E

T

T

V

I

E

E

S

A

G

G

F

F

M

M

T

T

K

K

D

D

L

L

A

A

I

A

L

C

I

I

G

K

-

G

-

L

P

P

D

N

-

V

-

Q

-

R

Q

S

P

D

W

Y

L

L

T

N

T

T

K

F

Q

E

F

F

L

M

D

D

K

K

L

L

D

G

E

E

N

N

L

L

Q

K

K

I

K

K

M

L

A

A

binding magnesium ion: D282 (= D274), D286 (= D278)

6bl2A Novel modes of inhibition of wild-type idh1: direct covalent modification of his315 with cmpd15 (see paper)
68% identity, 97% coverage: 10:404/407 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

Q

E

F

L

I

I

K

K

D

E

K

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

S

G

V

I

E

E

N

N

R

R

D

D

K

A

T

T

D

N

D

D

R

Q

V

V

T

T

V

K

E

D

S

A

A

A

N

E

A

A

I

I

K

K

Q

K

Y

H

G

N

V

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

T

E

E

E

F

F

N

K

L

L

K

K

K

Q

M

M

W

W

K

K

S

S

P

P

N

N

G

G

T

T

I

I

R

R

N

N

I

I

L

L

G

G

T

T

V

V

F

F

R

R

E

E

P

A

I

I

V

I

C

C

S

K

N

N

V

I

P

P

R

R

Y

L

V

V

P

S

G

G

W

W

T

V

K

K

P

P

I

I

G

G

R

R

H

H

A

A

F

Y

G

G

D

D

Q

Q

Y

Y

K

R

A

A

T

T

D

D

F

F

V

V

P

P

G

G

K

P

G

G

K

K

L

V

T

E

I

I

K

T

W

Y

V

T

P

P

E

S

G

D

G

G

G

T

E

Q

P

K

I

V

E

T

Q

Y

E

L

V

V

Y

H

D

N

F

F

P

E

-

E

A

G

S

G

G

G

V

V

A

A

M

M

G

G

M

M

Y

Y

N

N

L

Q

D

D

E

K

S

S

I

I

E

E

G

D

F

F

A

A

H

H

S

S

F

F

M

Q

Y

M

G

A

L

L

E

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

R

R

F

F

K

K

D

D

I

I

F

F

Q

Q

K

E

V

I

F

Y

D

D

E

K

H

Q

Y

Y

A

K

A

S

Q

Q

F

F

K

E

A

A

K

Q

G

K

L

I

V

W

Y

Y

E

E

H

H

R

R

L

L

I

I

D

D

M

M

V

V

A

A

S

Q

A

A

L

M

K

K

W

S

E

E

G

G

F

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

I

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

I

V

T

C

P

P

D

D

G

G

K

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

E

M

H

Y

Q

Q

K

K

G

G

K

Q

E

E

T
|
T

S

S

T

T

N

N

P

P

I

I

A

A

S

S

I

I

Y

F

A

A

W

W

T

T

Q

R

G

G

L

L

A

A

Y

H

R

R

G

A

K

K

F

L

D

D

N

N

T

N

P

K

D

E

V

L

V

A

K

F

F

F

A

A

E

N

T

A

L

L

E

E

R

E

V

V

C

S

V

I

E

E

T

T

V

I

E

E

S

A

G

G

F

F

M

M

T

T

K
|
K

D
|
D

L

L

A

A

I
x
A

L

C

I

I

G

K

-

G

-
x
L

P

P

D

N

-

V

-

Q

-

R

Q

S

P

D

W

Y

L

L

T

N

T

T

K

F

Q

E

F

F

L

M

D

D

K

K

L

L

D

G

E

E

N

N

L

L

Q

K

K

I

K

K

M

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 (= H308), V310 (= V311), R312 (= R313), H313 (= H314), T323 (= T324), K372 (= K373), D373 (= D374), A376 (≠ I377), L381 (vs. gap)

6bl1A Novel modes of inhibition of wild-type idh1: direct covalent modification of his315 with cmpd13 (see paper)
68% identity, 97% coverage: 10:404/407 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

Q

E

F

L

I

I

K

K

D

E

K

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

S

G

V

I

E

E

N

N

R

R

D

D

K

A

T

T

D

N

D

D

R

Q

V

V

T

T

V

K

E

D

S

A

A

A

N

E

A

A

I

I

K

K

Q

K

Y

H

G

N

V

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

T

E

E

E

F

F

N

K

L

L

K

K

K

Q

M

M

W

W

K

K

S

S

P

P

N

N

G

G

T

T

I

I

R

R

N

N

I

I

L

L

G

G

T

T

V

V

F

F

R

R

E

E

P

A

I

I

V

I

C

C

S

K

N

N

V

I

P

P

R

R

Y

L

V

V

P

S

G

G

W

W

T

V

K

K

P

P

I

I

G

G

R

R

H

H

A

A

F

Y

G

G

D

D

Q

Q

Y

Y

K

R

A

A

T

T

D

D

F

F

V

V

P

P

G

G

K

P

G

G

K

K

L

V

T

E

I

I

K

T

W

Y

V

T

P

P

E

S

G

D

G

G

G

T

E

Q

P

K

I

V

E

T

Q

Y

E

L

V

V

Y

H

D

N

F

F

P

E

-

E

A

G

S

G

G

G

V

V

A

A

M

M

G

G

M

M

Y

Y

N

N

L

Q

D

D

E

K

S

S

I

I

E

E

G

D

F

F

A

A

H

H

S

S

F

F

M

Q

Y

M

G

A

L

L

E

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

R

R

F

F

K

K

D

D

I

I

F

F

Q

Q

K

E

V

I

F

Y

D

D

E

K

H

Q

Y

Y

A

K

A

S

Q

Q

F

F

K

E

A

A

K

Q

G

K

L

I

V

W

Y

Y

E

E

H

H

R

R

L

L

I

I

D

D

M

M

V

V

A

A

S

Q

A

A

L

M

K

K

W

S

E

E

G

G

F

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

I

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

I

V

T

C

P

P

D

D

G

G

K

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

E
x
M

H

Y

Q

Q

K

K

G

G

K

Q

E

E

T

T

S

S

T

T

N

N

P

P

I

I

A

A

S

S

I

I

Y

F

A

A

W

W

T

T

Q

R

G

G

L

L

A

A

Y

H

R

R

G

A

K

K

F

L

D

D

N

N

T

N

P

K

D

E

V

L

V

A

K

F

F

F

A

A

E

N

T

A

L

L

E

E

R

E

V

V

C

S

V

I

E

E

T

T

V

I

E

E

S

A

G

G

F

F

M

M

T

T

K
|
K

D

D

L

L

A

A

I

A

L

C

I

I

G

K

-

G

-
x
L

P

P

D

N

-

V

-

Q

-

R

Q

S

P

D

W

Y

L

L

T

N

T

T

K

F

Q

E

F

F

L

M

D

D

K

K

L

L

D

G

E

E

N

N

L

L

Q

K

K

I

K

K

M

L

A

A

binding calcium ion: D273 (= D274), D277 (= D278)
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 (= H308), V310 (= V311), R312 (= R313), H313 (= H314), M316 (≠ E317), K372 (= K373), L381 (vs. gap)

6bl0A Novel modes of inhibition of wild-type idh1:direct covalent modification of his315 with cmpd11 (see paper)
68% identity, 97% coverage: 10:404/407 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

Q

E

F

L

I

I

K

K

D

E

K

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

S

G

V

I

E

E

N

N

R

R

D

D

K

A

T

T

D

N

D

D

R

Q

V

V

T

T

V

K

E

D

S

A

A

A

N

E

A

A

I

I

K

K

Q

K

Y

H

G

N

V

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

T

E

E

E

F

F

N

K

L

L

K

K

K

Q

M

M

W

W

K

K

S

S

P

P

N

N

G

G

T

T

I

I

R

R

N

N

I

I

L

L

G

G

T

T

V

V

F

F

R

R

E

E

P

A

I

I

V

I

C

C

S

K

N

N

V

I

P

P

R

R

Y

L

V

V

P

S

G

G

W

W

T

V

K

K

P

P

I

I

G

G

R

R

H

H

A

A

F

Y

G

G

D

D

Q

Q

Y

Y

K

R

A

A

T

T

D

D

F

F

V

V

P

P

G

G

K

P

G

G

K

K

L

V

T

E

I

I

K

T

W

Y

V

T

P

P

E

S

G

D

G

G

G

T

E

Q

P

K

I

V

E

T

Q

Y

E

L

V

V

Y

H

D

N

F

F

P

E

-

E

A

G

S

G

G

G

V

V

A

A

M

M

G

G

M

M

Y

Y

N

N

L

Q

D

D

E

K

S

S

I

I

E

E

G

D

F

F

A

A

H

H

S

S

F

F

M

Q

Y

M

G

A

L

L

E

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

R

R

F

F

K

K

D

D

I

I

F

F

Q

Q

K

E

V

I

F

Y

D

D

E

K

H

Q

Y

Y

A

K

A

S

Q

Q

F

F

K

E

A

A

K

Q

G

K

L

I

V

W

Y

Y

E

E

H

H

R

R

L

L

I

I

D

D

M

M

V

V

A

A

S

Q

A

A

L

M

K

K

W

S

E

E

G

G

F

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

I

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

I

V

T

C

P

P

D

D

G

G

K

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

E

M

H

Y

Q

Q

K

K

G

G

K

Q

E

E

T

T

S

S

T

T

N
|
N

P

P

I

I

A

A

S

S

I

I

Y

F

A

A

W

W

T

T

Q

R

G

G

L

L

A

A

Y

H

R

R

G

A

K

K

F

L

D

D

N

N

T

N

P

K

D

E

V

L

V

A

K

F

F

F

A

A

E

N

T

A

L

L

E

E

R

E

V

V

C

S

V

I

E

E

T

T

V

I

E

E

S

A

G

G

F

F

M

M

T

T

K
|
K

D

D

L

L

A

A

I

A

L

C

I

I

G

K

-

G

-
x
L

P

P

D

N

-

V

-

Q

-

R

Q

S

P

D

W

Y

L

L

T

N

T

T

K

F

Q

E

F

F

L

M

D

D

K

K

L

L

D

G

E

E

N

N

L

L

Q

K

K

I

K

K

M

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 (= H308), V310 (= V311), R312 (= R313), H313 (= H314), N326 (= N327), K372 (= K373), L381 (vs. gap)

6bkyA Novel binding modes of inhibition of wild-type idh1: allosteric inhibition with cmpd2 (see paper)
68% identity, 97% coverage: 10:404/407 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

Q

E

F

L

I

I

K

K

D

E

K

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

S

G

V

I

E

E

N

N

R

R

D

D

K

A

T

T

D

N

D

D

R

Q

V

V

T

T

V

K

E

D

S

A

A

A

N

E

A

A

I

I

K

K

Q

K

Y

H

G

N

V

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

T

E

E

E

F

F

N

K

L

L

K

K

K

Q

M

M

W

W

K

K

S

S

P

P

N

N

G

G

T

T

I

I

R

R

N

N

I

I

L

L

G

G

T

T

V

V

F

F

R

R

E

E

P

A

I

I

V

I

C

C

S

K

N

N

V

I

P

P

R

R

Y

L

V

V

P

S

G

G

W

W

T

V

K

K

P

P

I

I

G

G

R

R

H

H

A

A

F

Y

G

G

D

D

Q

Q

Y

Y

K

R

A

A

T

T

D

D

F

F

V

V

P

P

G

G

K

P

G

G

K

K

L

V

T

E

I

I

K

T

W

Y

V

T

P

P

E

S

G

D

G

G

G

T

E

Q

P

K

I

V

E

T

Q

Y

E

L

V

V

Y

H

D

N

F

F

P

E

-

E

A

G

S

G

G

G

V

V

A

A

M

M

G

G

M

M

Y

Y

N

N

L

Q

D

D

E

K

S

S

I

I

E

E

G

D

F

F

A

A

H

H

S

S

F

F

M

Q

Y

M

G

A

L

L

E

S

R

K

G

G

Y

W

P

P

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A

binding 4,5,6,7-tetrabromo-1h,3h-benzimidazol-2-one: V253 (= V254), M257 (≠ L258), Q275 (= Q276), S278 (≠ I279)

Query Sequence

>AZOBR_RS10995 FitnessBrowser__azobra:AZOBR_RS10995
MTKIKVANPVVELDGDEMTRIIWQFIKDKLILPYLDVDLKYYDLSVENRDKTDDRVTVES
ANAIKQYGVGVKCATITPDEARVTEFNLKKMWKSPNGTIRNILGGTVFREPIVCSNVPRY
VPGWTKPIIIGRHAFGDQYKATDFVVPGKGKLTIKWVPEGGGEPIEQEVYDFPASGVAMG
MYNLDESIEGFAHSSFMYGLERGYPVYLSTKNTILKAYDGRFKDIFQKVFDEHYAAQFKA
KGLVYEHRLIDDMVASALKWEGGFVWACKNYDGDVQSDIVAQGFGSLGLMTSVLITPDGK
TVEAEAAHGTVTRHYREHQKGKETSTNPIASIYAWTQGLAYRGKFDNTPDVVKFAETLER
VCVETVESGFMTKDLAILIGPDQPWLTTKQFLDKLDENLQKKMAAWA

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