SitesBLAST

S109 (≠ T46) to W: in D2HGA1; uncertain significance; significant loss of catalytic activity; dbSNP:rs142050154
N127 (≠ V64) to K: in D2HGA1; uncertain significance; complete loss of catalytic activity; dbSNP:rs762857195
G131 (= G68) to V: in D2HGA1; uncertain significance; complete loss of catalytic activity
I147 (≠ V84) to S: in D2HGA1; uncertain significance; severe phenotype; almost complete loss of catalytic activity; dbSNP:rs121434361
M153 (= M90) to T: in D2HGA1; uncertain significance; significant loss of catalytic activity; to V: in D2HGA1; uncertain significance; significant loss of catalytic activity; dbSNP:rs1432270139
C172 (≠ A109) to Y: in D2HGA1; uncertain significance; moderate reduction in catalytic activity; dbSNP:rs773735172
P189 (≠ A126) to L: in D2HGA1; uncertain significance; almost complete loss of catalytic activity; dbSNP:rs587783517
A205 (= A142) to V: in D2HGA1; uncertain significance; almost complete loss of catalytic activity; dbSNP:rs750889931
A231 (= A168) to V: in D2HGA1; uncertain significance; significant loss of catalytic activity
G233 (= G170) to S: in D2HGA1; uncertain significance; no effect on catalytic activity; dbSNP:rs374535734
D375 (≠ S314) to Y: in D2HGA1; uncertain significance; moderate reduction in catalytic activity; dbSNP:rs267606759
R386 (= R325) binding (R)-2-hydroxyglutarate; binding (R)-lactate; binding (R)-malate; mutation to A: Loss of catalytic activity.
T390 (≠ A329) binding (R)-2-hydroxyglutarate; binding (R)-malate; mutation to A: Significantly reduced catalytic activity.
V399 (≠ M338) to M: in D2HGA1; uncertain significance; moderate reduction in catalytic activity; dbSNP:rs746519212
K401 (≠ A340) binding (R)-2-hydroxyglutarate; binding (R)-malate; mutation to A: Loss of catalytic activity.
R419 (≠ E358) to H: in D2HGA1; uncertain significance; moderate reduction in catalytic activity; dbSNP:rs199908032
A426 (= A368) to T: in D2HGA1; uncertain significance; no effect on catalytic activity; dbSNP:rs146578303
H434 (= H375) binding Zn(2+); mutation to A: Loss of catalytic activity.
G436 (= G377) to V: slight reduction in catalytic activity
N439 (= N380) to D: in D2HGA1; uncertain significance; mild phenotype; moderate reduction in catalytic activity; dbSNP:rs121434362
H441 (= H382) binding Zn(2+); mutation to A: Loss of catalytic activity.
N443 (≠ V384) binding (R)-2-hydroxyglutarate; mutation to A: Significantly reduced catalytic activity.
V444 (= V385) to A: in D2HGA1; uncertain significance; severe phenotype; significant reduction in catalytic activity; dbSNP:rs121434360
A446 (vs. gap) to V: in D2HGA1; uncertain significance; moderate reduction in catalytic activity; dbSNP:rs746956176
E475 (= E412) binding Zn(2+); mutation to A: Loss of catalytic activity.
H476 (= H413) binding (R)-2-hydroxyglutarate; binding (R)-lactate; binding (R)-malate; mutation to A: Loss of catalytic activity.
G477 (= G414) to R: in D2HGA1; uncertain significance; almost complete loss of catalytic activity; dbSNP:rs1453924640

Sites not aligning to the query:

15 R → G: in dbSNP:rs4675887
169:521 natural variant: Missing (in D2HGA1; uncertain significance)
400:521 natural variant: Missing (in D2HGA1; uncertain significance; complete loss of catalytic activity)

P39976 D-2-hydroxyglutarate--pyruvate transhydrogenase DLD3; D-2HG--pyruvate transhydrogenase DLD3; (R)-2-hydroxyglutarate--pyruvate transhydrogenase; D-lactate dehydrogenase [cytochrome] 3; D-lactate ferricytochrome C oxidoreductase; D-LCR; EC 1.1.99.40; EC 1.1.2.4 from Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast) (see paper)
36% identity, 91% coverage: 40:454/456 of query aligns to 71:496/496 of P39976

query
sites
P39976

I

I

V

L

R

L

P

P

R

N

T

S

T

T

E

D

E

K

V

V

S

S

R

K

I

I

M

M

A

K

L

Y

C

C

H

N

A

D

Q

K

E

K

Q

L

R

A

V

V

P

P

W

Q

G

G

L

N

T

T

G

D

L

L

V

V

D

G

G

A

I

S

T

V

C

P

E

V

A

F

G

D

D

E

L

I

V

V

L

L

S

S

M

L

E

R

R

N

M

M

Q

N

N

K

I

V

E

R

H

D

C

F

E

D

P

P

D

V

A

S

G

G

T

T

L

F

R

K

V

C

Q

D

A

A

G

G

A

V

V

V

L

M

Q

R

S

D

V

A

Q

H

D

Q

A

F

A

L

A

H

E

D

A

H

G

D

W

H

Q

I

F

F

A

P

V

L

D

D

L

L

G

P

G

S

R

R

G

N

S

N

A

C

Q

Q

I

V

G

G

L

V

V

V

A

S

T

T

N

N

A

A

G

G

N

L

A

N

V

F

V

L

R

R

Y

Y

G

G

M

S

M

L

R

H

E

G

Q

N

V

V

L

L

G

G

L

L

E

E

V

V

L

L

A

P

D

N

G

G

R

E

V

I

M

I

S

S

S

N

L

I

N

N

E

A

V

L

L

R

K

K

N

D

N

N

A

T

G

G

Y

Y

D

D

M

L

K

K

Q

Q

L

L

F

F

I

I

G

G

S

A

E

E

G

G

T

T

L

I

G

G

I

V

V

V

T

T

R

G

A

V

V

S

L

I

R

V

L

A

R

A

P

A

A

K

A

P

N

K

A

A

R

L

Q

N

T

A

A

V

F

F

L

F

G

G

M

I

N

E

S

N

F

F

D

D

D

T

V

V

A

Q

A

K

L

L

L

F

R

V

H

K

L

A

Q

K

S

S

H

E

L

L

E

S

G

E

K

I

L

L

S

S

S

A

F

F

E

E

V

F

M

M

W

D

A

R

N

G

H

S

Y

I

R

E

F

C

M

T

V

I

E

E

E

Y

L

L

A

K

T

D

H

L

Q

P

T

F

F

P

L

L

P

E

V

N

D

Q

Y

H

P

N

Y

F

Y

Y

V

V

L

L

V

I

E

E

S

T

E

S

G

G

Q

S

F

N

P

K

D

R

R

H

E

D

A

E

L

K

F

L

T

T

S

A

V

F

L

L

G

K

E

D

L

T

M

T

E

D

E

S

G

K

T

L

I

I

A

S

D

E

A

G

V

M

I

M

A

A

Q

K

S

D

G

K

Q

A

Q

D

A

F

E

D

Q

R

L

L

W

W

A

T

M

W

R

R

D

K

D

S

V

V

A

P

S

T

L

A

I

C

E

N

A

S

M

Y

A

G

P

G

M

M

A

Y

A

K

F

Y

D

D

I

M

S

S

L

L

P

Q

L

L

R

K

D

D

M

L

Q

Y

T

S

Y

V

V

S

A

A

M

V

E

T

Q

E

-

R

-

L

-

N

-

A

G

G

L

L

A

I

K

G

R

D

L

A

P

P

E

K

A

P

R

V

V

V

V

K

V

S

-

C

-

G

F

Y

G

G

H

H

L

V

G

G

D

D

G

G

N

N

I

I

H

H

L

L

V

N

V

I

G

A

N

V

I

R

P

E

D

F

H

T

K

K

A

Q

V

I

E

E

E

D

V

L

-

L

-

E

-

P

-

F

V

V

Y

Y

G

E

E

Y

L

I

R

A

N

S

L

K

G

K

G

G

S

S

I

I

S

S

A

A

E

E

H

H

G

G

I

I

G

G

L

F

E

H

K

K

R

K

D

G

Y

K

L

L

A

H

Y

Y

S

T

K

R

G

S

E

D

I

I

E

E

I

I

D

R

L

F

M

M

R

K

T

D

L

I

K

K

H

N

A

H

L

Y

D

D

P

P

K

N

G

G

I

I

L

L

N

N

P

P

G

Y

K

K

V

Y

I

I

Sites not aligning to the query:

17 modified: Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)

8jdzA Crystal structure of mldhd in complex with 2-keto-3-methylvaleric acid (see paper)
30% identity, 99% coverage: 2:454/456 of query aligns to 4:454/454 of 8jdzA

query
sites
8jdzA

N

D

L

F

I

V

E

E

Q

A

L

L

Q

K

Q

A

I

V

V

V

G

G

A

S

N

P

G

H

V

V

L

S

T

T

G

A

D

S

D

A

V

V

R

R

S

E

R

Q

P

H

N

G

H

H

S

D

W
x
E

G

S

R

M

G

H

E

R

C

C

-

Q

P

P

A

P

M

D

A

A

I

V

V

V

R

W

P

P

R

Q

T

N

T

V

E

D

E

Q

V

V

S

S

R

R

I

V

M

A

A

S

L

L

C

C

H

Y

A

N

Q

Q

E

G

Q

V

R

P

V

I

P
|
P

W

F

G
|
G

G
x
T

L
x
G

T
|
T

G
|
G

L

V

V

E

D

G

G
|
G

I
x
V

T

C

C

A

E

V

A

Q

G

G

D

G

L

V

V

C

L

I

S

N

M
x
L

E

T

R

H

M

M

Q

D

N

Q

I

I

E

T

H

E

C

L

E

N