SitesBLAST

SitesBLAST – Find functional sites

SitesBLAST

Comparing H281DRAFT_00810 FitnessBrowser__Burk376:H281DRAFT_00810 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 19 hits to proteins with known functional sites (download)

Q5F8J4 NAD(+)-dependent homoserine dehydrogenase; NAD(+)-dependent HSD; NgHSD; EC 1.1.1.3 from Neisseria gonorrhoeae (strain ATCC 700825 / FA 1090) (see paper)
59% identity, 100% coverage: 1:443/443 of query aligns to 1:434/435 of Q5F8J4

query
sites
Q5F8J4

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L45 (≠ R45) mutation to R: Shows a marked increase in the catalytic efficiency with NADP(+).
LS 45:46 (≠ RN 45:46) mutation to RD: Does not impair the catalytic activity with NAD(+). Slightly increases the activity, but slightly decreases the affinity for NADP(+).; mutation to RR: Causes a shift in coenzyme preference from NAD(+) to NADP(+) by a factor of 974. Shows a slight decrease in the catalytic efficiency with NAD(+) and a 4.5-fold increase in catalytic efficiency with NADP(+).

6dzsA Mycobacterial homoserine dehydrogenase thra in complex with NADP
40% identity, 99% coverage: 2:440/443 of query aligns to 3:429/431 of 6dzsA

query
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6dzsA

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binding nadp nicotinamide-adenine-dinucleotide phosphate: G11 (= G10), L12 (≠ F11), G13 (= G12), N14 (≠ T13), V15 (= V14), V45 (= V44), R46 (= R45), R47 (≠ K49), R52 (≠ L54), I63 (≠ F67), L78 (≠ M82), M79 (≠ I83), P84 (≠ V88), A102 (= A106), K104 (= K108), G306 (= G305), T310 (= T309)

4pg7A Crystal structure of s. Aureus homoserine dehydrogenase at ph7.5 (see paper)
41% identity, 77% coverage: 1:341/443 of query aligns to 2:324/402 of 4pg7A

query
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4pg7A

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active site: D190 (= D204), K194 (= K208)
binding lysine: R215 (≠ E229), G219 (≠ K233)

Sites not aligning to the query:

binding lysine: 394, 395

6a0tB Homoserine dehydrogenase k99a mutant from thermus thermophilus hb8 complexed with hse and NADP+ (see paper)
36% identity, 74% coverage: 1:330/443 of query aligns to 1:312/332 of 6a0tB

query
sites
6a0tB

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A

R

F

G

G

I

V

E

-

V

V

A

P

R

R

-

F

-

L

-

G

I

V

A
x
L

V
|
V

R
|
R

N
x
D

P

P

A

R

K
|
K

A

P

T
x
R

A

A

A

I

L

-

G

-

A

-

D

-

A

-

P

P

S

Q

V

E

A

L

L

L

-

R

T

A

D

E

D

P

F

F

N

D

A

L

V

L

V

-

D

-

P

-

S

E

I

A

D

D

I

L

V

V

A

V

E

E

M
x
A

I
x
M

G
|
G

G

G

T

V

G

E

V

A

A

P

R

L

D

R

L

L

V

V

L

L

R

P

A

A

I

L

K

E

N

A

R

G

K

I

H

P

V

L

V

I

T

T

A
|
A

N
|
N

K

K

A

A

L

L

A

A

V

-

H

-

G

-

T

-

E

E

I

A

F

W

E

E

A

S

A

L

R

R

-

P

-

F

A

A

N

E

G

E

V

G

M

L

V

I

A

Y

F

H

E

E

A

A

A

S

V

V

A

M

G

A

G

G

I

T

P

P

I

A

I

L

K

S

A

F

L

L

R

-

E

E

G

T

L

L

T

R

A

G

N

S

R

E

I

L

Q

L

Y

E

I

L

A

H

G

G

I

I

I

L

N
|
N

G
|
G

T
|
T

T

T

N

L

Y

Y

I

I

L

L

S

Q

E

E

M

M

R

-

D

E

R

K

G

G

L

R

D

T

F

Y

A

A

T

E

A

A

L

L

K

L

A

E

A

A

Q

Q

E

R

L

L

G
|
G

Y
|
Y

A

A

E
|
E

A

A

D

D

P

P

T

T

F

L

D
|
D

I

V

E

E

G

G

V

I

D
|
D

A

A

H

H

K
|
K

A

L

T

T

I

L

M

L

S

A

A

R

I

L

A

L

F

V

G

D

V

P

P

G

V

F

Q

P

F

F

D

A

R

E

A

V

Y

E

V

A

E

Q

G

G

I

I

S

A

K

R

L

L

A

T

A

P

I

E

D

V

I

L

K

Q

Y

K

A

A

E

E

E

A

L

R

G

G

Y

E

R

R

I

V

K

R

L

L

L

-

G

-

I

V

A

A

R

S

R

L

T

F

D

G

K

E

G

G

I

G

E

R

L

W

R

R

-

A

V

V

H

A

P

P

T

R

L

R

I

L

P

P

E

Q

K

D

R

H

L

P

L

L

A

A

N

R

V

A

E

R

G

G

A

-

M

-

N

N

A

A

V

L

V

W

V

V

H

R

G

A

D

R

A

P

V

L

G

G

T

E

T

A

L

F

Y

V

Y

T

G

G

K

P

G

G

A
|
A

G
|
G

A

G

E

G

P

A

T
|
T

A

A

S

S

A

G

V

L

V

F

A

A

D

D

L

L

V

L

D

-

V

-

T

-

R

R

L

F

H

L

T

S

A

G

D

A

P

P

E

G

H

H

active site: D191 (= D204), K195 (= K208)
binding l-homoserine: N150 (= N162), G151 (= G163), T152 (= T164), Y178 (= Y191), E180 (= E193), D186 (= D199), K195 (= K208)
binding nadp nicotinamide-adenine-dinucleotide phosphate: G10 (= G10), G11 (≠ F11), G12 (= G12), T13 (= T13), V14 (= V14), L42 (≠ A43), V43 (= V44), R44 (= R45), D45 (≠ N46), K48 (= K49), R50 (≠ T51), A73 (≠ M82), M74 (≠ I83), G75 (= G84), A97 (= A106), N98 (= N107), G177 (= G190), E180 (= E193), A289 (= A304), G290 (= G305), T294 (= T309)

6a0sA Homoserine dehydrogenase from thermus thermophilus hb8 complexed with hse and NADPH (see paper)
36% identity, 74% coverage: 1:330/443 of query aligns to 1:312/331 of 6a0sA

query
sites
6a0sA

M

M

E

E

P

A

I

L

K

K

V

I

G

A

L

L

G

G

F
x
G

G
|
G

T
|
T

V
|
V

G

G

S

S

G

A

T

F

F

Y

T

N

V

L

L

V

R

L

R

E

N

R

Q

A

E

E

I

L

K

-

R

-

A

S

G

A

R

F

G

G

I

V

E

-

V

V

A

P

R

R

-

F

-

L

-

G

I

V

A
x
L

V
|
V

R
|
R

N
x
D

P

P

A

R

K
|
K

A

P

T
x
R

A

A

A

I

L

-

G

-

A

-

D

-

A

-

P

P

S

Q

V

E

A

L

L

L

-

R

T

A

D

E

D

P

F

F

N

D

A

L

V

L

V

-

D

-

P

-

S

E

I

A

D

D

I

L

V

V

A

V

E

E

M
x
A

I
x
M

G

G

T

V

G

E

V

A

A

P

R

L

D

R

L

L

V

V

L

L

R

P

A

A

I

L

K

E

N

A

R

G

K

I

H

P

V

L

V

I

T

T

A
|
A

N

N

K
|
K

A

A

L

L

A

A

V

-

H

-

G

-

T

-

E

E

I

A

F

W

E

E

A

S

A

L

R

R

-

P

-

F

A

A

N

E

G

E

V

G

M

L

V

I

A

Y

F

H

E

E

A

A

A

S

V

V

A

M

G

A

G

G

I

T

P

P

I

A

I

L

K

S

A

F

L

L

R

-

E

E

G

T

L

L

T

R

A

G

N

S

R

E

I

L

Q

L

Y

E

I

L

A

H

G

G

I

I

I

L

N
|
N

G
|
G

T
|
T

T

T

N

L

Y

Y

I

I

L

L

S

Q

E

E

M

M

R

-

D

E

R

K

G

G

L

R

D

T

F

Y

A

A

T

E

A

A

L

L

K

L

A

E

A

A

Q

Q

E

R

L

L

G
|
G

Y
|
Y

A

A

E
|
E

A

A

D

D

P

P

T

T

F

L

D
|
D

I

V

E

E

G

G

V

I

D
|
D

A

A

H

H

K
|
K

A

L

T

T

I

L

M

L

S

A

A

R

I

L

A

L

F

V

G

D

V

P

P

G

V

F

Q

P

F

F

D

A

R

E

A

V

Y

E

V

A

E

Q

G

G

I

I

S

A

K

R

L

L

A

T

A

P

I

E

D

V

I

L

K

Q

Y

K

A

A

E

E

E

A

L

R

G

G

Y

E

R

R

I

V

K

R

L

L

L

-

G

-

I

V

A

A

R

S

R

L

T

F

D

G

K

E

G

G

I

G

E

R

L

W

R

R

-

A

V

V

H

A

P

P

T

R

L

R

I

L

P

P

E

Q

K

D

R

H

L

P

L

L

A

A

N

R

V

A

E

R

G

G

A

-

M

-

N

N

A

A

V

L

V

W

V

V

H

R

G

A

D

R

A

P

V

L

G

G

T

E

T

A

L

F

Y

V

Y

T

G

G

K

P

G

G

A
|
A

G
|
G

A

G

E

G

P

A

T
|
T

A

A

S

S

A

G

V

L

V

F

A

A

D

D

L

L

V

L

D

-

V

-

T

-

R

R

L

F

H

L

T

S

A

G

D

A

P

P

E

G

H

H

active site: D191 (= D204), K195 (= K208)
binding l-homoserine: K99 (= K108), N150 (= N162), G151 (= G163), T152 (= T164), Y178 (= Y191), E180 (= E193), D186 (= D199), K195 (= K208)
binding nadph dihydro-nicotinamide-adenine-dinucleotide phosphate: G11 (≠ F11), G12 (= G12), T13 (= T13), V14 (= V14), L42 (≠ A43), V43 (= V44), R44 (= R45), D45 (≠ N46), K48 (= K49), R50 (≠ T51), A73 (≠ M82), M74 (≠ I83), A97 (= A106), K99 (= K108), G177 (= G190), E180 (= E193), A289 (= A304), G290 (= G305), T294 (= T309)

2ejwA Homoserine dehydrogenase from thermus thermophilus hb8
36% identity, 74% coverage: 1:330/443 of query aligns to 1:312/331 of 2ejwA

query
sites
2ejwA

M

M

E

E

P

A

I

L

K

K

V

I

G

A

L

L

G

G

F

G

G

G

T

T

V

V

G

G

S

S

G

A

T

F

F

Y

T

N

V

L

L

V

R

L

R

E

N

R

Q

A

E

E

I

L

K

-

R

-

A

S

G

A

R

F

G

G

I

V

E

-

V

V

A

P

R

R

-

F

-

L

-

G

I

V

A

L

V

V

R

R

N

D

P

P

A

R

K

K

A

P

T

R

A

A

A

I

L

-

G

-

A

-

D

-

A

-

P

P

S

Q

V

E

A

L

L

L

-

R

T

A

D

E

D

P

F

F

N

D

A

L

V

L

V

-

D

-

P

-

S

E

I

A

D

D

I

L

V

V

A

V

E

E

M

A

I

M

G

G

T

V

G

E

V

A

A

P

R

L

D

R

L

L

V

V

L

L

R

P

A

A

I

L

K

E

N

A

R

G

K

I

H

P

V

L

V

I

T

T

A

A

N

N

K

K

A

A

L

L

A

A

V

-

H

-

G

-

T

-

E

E

I

A

F

W

E

E

A

S

A

L

R

R

-

P

-

F

A

A

N

E

G

E

V

G

M

L

V

I

A

Y

F

H

E
|
E

A

A

A

S

V
|
V

A
x
M

G
x
A

G

G

I
x
T

P

P

I

A

I

L

K

S

A

F

L

L

R

-

E

E

G

T

L

L

T

R

A

G

N

S

R

E

I

L

Q

L

Y

E

I

L

A

H

G

G

I

I

I

L

N

N

G

G

T

T

N

L

Y

Y

I

I

L

L

S

Q

E

E

M

M

R

-

D

E

R

K

G

G

L

R

D

T

F

Y

A

A

T

E

A

A

L

L

K

L

A

E

A

A

Q

Q

E

R

L

L

G

G

Y

Y

A

A

E

E

A

A

D

D

P

P

T

T

F

L

D

D

I

V

E

E

G

G

V

I

D
|
D

A

A

H

H

K
|
K

A

L

T

T

I

L

M

L

S

A

A

R

I

L

A

L

F

V

G

D

V

P

P

G

V

F

Q

P

F

F

D

A

R

E

A

V

Y

E

V

A

E

Q

G

G

I

I

S

A

K

R

L

L

A

T

A

P

I

E

D

V

I

L

K

Q

Y

K

A

A

E

E

E

A

L

R

G

G

Y

E

R

R

I

V

K

R

L

L

L

-

G

-

I

V

A

A

R

S

R

L

T

F

D

G

K

E

G

G

I

G

E

R

L

W

R

R

-

A

V

V

H

A

P

P

T

R

L

R

I

L

P

P

E

Q

K

D

R

H

L

P

L

L

A

A

N

R

V

A

E

R

G

G

A

-

M

-

N

N

A

A

V

L

V

W

V

V

H

R

G

A

D

R

A

P

V

L

G

G

T

E

T

A

L

F

Y

V

Y

T

G

G

K

P

G

G

A

A

G

G

A

G

E

G

P

A

T

T

A

A

S

S

A

G

V

L

V

F

A

A

D

D

L

L

V

L

D

-

V

-

T

-

R

R

L

F

H

L

T

S

A

G

D

A

P

P

E

G

H

H

active site: D191 (= D204), K195 (= K208)
binding magnesium ion: E121 (= E132), V124 (= V135), M125 (≠ A136), A126 (≠ G137), T128 (≠ I139)

7f4cA The crystal structure of the immature holo-enzyme of homoserine dehydrogenase complexed with NADP and 1,4-butandiol from the hyperthermophilic archaeon sulfurisphaera tokodaii. (see paper)
34% identity, 72% coverage: 4:322/443 of query aligns to 1:297/300 of 7f4cA

query
sites
7f4cA

I

M

K

K

V

L

G

L

L

L

L
x
F

G
|
G

F
x
Y

G
|
G

T
x
N

V
|
V

G

G

S

K

G

A

T

F

F

R

T

K

V

L

L

L

-

H

R

E

R

K

N

R

Q

S

E

P

E

E

I

L

K

N

R

D

R

V

A

I

G

I

R

G

G

G

I

I

E

V

V
x
T

A
x
R

R
|
R

-

G

I

I

A

M

V

L

R

Q

N

D

P

K

A

E

K

D

A

F

T

T

A

P

A

D

L

L

G

E

A

G

D

D

A

V

P

F

S

K

V

A

A

-

L

-

T

-

D

-

F

F

N

E

A

K

V

I

V

K

D

P

D

D

P

I

S

I

I

V

D

D

I
x
V

V
x
S

A
x
S

E

A

M

N

I

Y

G

N

T

G

G

E

V

P

A

S

R

L

D

S

L

L

V

Y

L

K

R

E

A

A

I

I

K

K

N

D

R

G

K

V

H

N

V

I

T

T

A
x
T

N

N

K
|
K

A

A

L

P

L

L

A

A

V

L

H

A

G

F

T

N

E

E

I

I

F

F

E

S

A

L

A

A

R

R

A

S

N

K

G

G

V

V

M

K

V

I

A

G

F

F

E

Q

A
x
G

A

T

V

V

A

M

G
x
S

G

G

I

T

P

P

I

S

I

I

K

N

A

L

L

Y

R

R

E

V

G

-

L

L

T

P

A

G

N

S

R

R

I

V

Q

I

Y

K

I

I

A

R

G

G

I

I

I

L

N

N

G

G

T

T

N

N

Y

F

I

I

L

L

S

T

E

L

M

M

R

-

D

N

R

K

G

G

L

V

D

S

F

F

A

E

T

E

A

A

L

L

K

K

A

E

A

A

Q

Q

E

R

L

R

G

G

Y

Y

A

A

E
|
E

A

E

D

D

P

P

T

T

F

L

D

D

I

I

E

N

G

G

V

F

D

D

A

A

H

A

K

K

A

I

T

T

I

I

M

L

S

A

A

N

I

F

A

M

F

I

G

G

V

N

P

S

V

V

Q

T

F

I

D

K

R

D

A

V

Y

K

V

F

E

E

G

G

I

I

S

N

K

R

L

-

A

-

I

-

D

D

I

L

K

K

Y

-

A

-

E

-

L

-

G

-

Y

-

R

-

I

I

K

K

L

L

L

I

G

A

I

Y

A

A

R

D

R

E

T

K

D

-

K

-

G

-

I

-

E

E

L

V

R

W

V

V

H

K

P

P

T

L

L

P

I

I

P

S

E

Q

K

D

R

D

L

P

L

L

A

Y

N

N

V

V

E

D

G

G

A

V

M

E

N

N

A

A

V

L

V

E

V

I

H

T

G

T

D

D

A

-

V

I

G

Q

T

S

T

I

L

L

Y

I

Y

R

G

G

K

P

G

G

A

A

G
|
G

A

P

E

V

P

N

T
x
A

A

A

S

Y

A

G

V

A

V

L

A

S

D

D

L

L

V

I

D

L

V

L

T

K

R

R

binding nadp nicotinamide-adenine-dinucleotide phosphate: F6 (≠ L9), G7 (= G10), Y8 (≠ F11), G9 (= G12), N10 (≠ T13), V11 (= V14), T37 (≠ V39), R38 (≠ A40), R39 (= R41), V72 (≠ I78), S73 (≠ V79), S74 (≠ A80), T100 (≠ A106), K102 (= K108), G127 (≠ A133), S131 (≠ G137), E185 (= E193), G280 (= G305), A284 (≠ T309)

5x9dA Crystal structure of homoserine dehydrogenase in complex with l- cysteine and NAD (see paper)
33% identity, 72% coverage: 4:322/443 of query aligns to 1:299/302 of 5x9dA

query
sites
5x9dA

I

M

K

K

V

L

G

L

L

L

L
x
F

G
|
G

F
x
Y

G
|
G

T
x
N

V
|
V

G

G

S

K

G

A

T

F

F

R

T

K

V

L

L

L

-

H

R

E

R

K

N

R

Q

S

E

P

E

E

I

L

K

N

R

D

R

V

A

I

G

I

R

G

G

G

I

I

E

V

V
x
T

A
x
R

R

R

-

G

I

I

A

M

V

L

R

Q

N

D

P

K

A

E

K

D

A

F

T

T

A

P

A

D

L

L

G

E

A

G

D

D

A

-

P

-

S

-

V

-

A

-

L

V

T

F

D

K

D

A

F

F

N

E

A

K

V

I

V

K

D

P

D

D

P

I

S

I

I

V

D

D

I
x
V

V
x
S

A
x
S

E

A

M

N

I

Y

G

N

T

G

G

E

V
x
P

A

S

R

L

D

S

L

L

V

Y

L

K

R

E

A

A

I

I

K

K

N

D

R

G

K

V

H

N

V

I

T

T

A
x
T

N
|
N

K
|
K

A

A

L

P

L

L

A

A

V

L

H

A

G

F

T

N

E

E

I

I

F

F

E

S

A

L

A

A

R

R

A

S

N

K

G

G

V

V

M

K

V

I

A

G

F

F

E

Q

A
x
G

A

T

V

V

A

M

G
x
S

G

G

I

T

P

P

I

S

I

I

K

N

A

L

L

Y

R

R

E

V

G

-

L

L

T

P

A

G

N

S

R

R

I

V

Q

I

Y

K

I

I

A

R

G

G

I

I

I

L

N
|
N

G
|
G

T
|
T

T

T

N

N

Y

F

I

I

L

L

S

T

E

L

M

M

R

-

D

N

R

K

G

G

L

V

D

S

F

F

A

E

T

E

A

A

L

L

K

K

A

E

A

A

Q

Q

E

R

L

R

G

G

Y
|
Y

A
|
A

E
|
E

A

E

D

D

P

P

T

T

F

L

D
|
D

I

I

E

N

G

G

V

F

D
|
D

A

A

H

A

K
|
K

A

I

T

T

I

I

M

L

S

A

A

N

I

F

A

M

F

I

G

G

V

N

P

S

V

V

Q

T

F

I

D

K

R

D

A

V

Y

K

V

F

E

E

G

G

I

I

S

N

K

R

L

-

A

-

I

-

D

-

I

-

K

-

Y

-

A

-

E

D

E

P

L

K

G

N

Y

E

R

K

I

I

K

K

L

L

L

I

G

A

I

Y

A

A

R

D

R

E

T

K

D

-

K

-

G

-

I

-

E

E

L

V

R

W

V

V

H

K

P

P

T

L

L

P

I

I

P

S

E

Q

K

D

R

P

L

L

L

Y

A

-

N

N

V

V

E

D

G

G

A

V

M

E

N

N

A

A

V

L

V

E

V

I

H

T

G

T

D

D

A

-

V

I

G

Q

T

S

T

I

L

L

Y

I

Y

R

G

G

K

P

G

G

A
|
A

G
|
G

A

P

E

V

P

N

T
x
A

A

A

S

Y

A

G

V

A

V

L

A

S

D

D

L

L

V

I

D

L

V

L

T

K

R

R

active site: D196 (= D204), K200 (= K208)
binding (2R)-3-[[(4S)-3-aminocarbonyl-1-[(2R,3R,4S,5R)-5-[[[[(2R,3S,4R,5R)-5-(6-aminopurin-9-yl)-3,4-bis(oxidanyl)oxolan-2-yl]methoxy-oxidanyl-phosphoryl]oxy-oxidanyl-phosphoryl]oxymethyl]-3,4-bis(oxidanyl)oxolan-2-yl]-4H-pyridin-4-yl]sulfanyl]-2-azanyl-propanoic acid: F6 (≠ L9), G7 (= G10), Y8 (≠ F11), G9 (= G12), N10 (≠ T13), V11 (= V14), T37 (≠ V39), R38 (≠ A40), V72 (≠ I78), S73 (≠ V79), S74 (≠ A80), P82 (≠ V88), T100 (≠ A106), N101 (= N107), K102 (= K108), G127 (≠ A133), S131 (≠ G137), N155 (= N162), G156 (= G163), T157 (= T164), Y183 (= Y191), A184 (= A192), E185 (= E193), D191 (= D199), D196 (= D204), K200 (= K208), A281 (= A304), G282 (= G305), A286 (≠ T309)

4xb1A Hyperthermophilic archaeal homoserine dehydrogenase in complex with NADPH (see paper)
32% identity, 49% coverage: 103:321/443 of query aligns to 111:312/319 of 4xb1A

query
sites
4xb1A

V

V

T

T

A
x
S

N

N

K
|
K

A

P

L

P

L

I

A

A

V

N

H

Y

G

Y

T

D

E

E

I

L

F

M

E

N

A

L

A

A

R

K

A

E

N

N

G

N

V

A

M

G

V

I

A

F

F

F

E

E

A
x
S

A

T

V

V

A

M

G

A

G

G

I

T

P

P

I

I

K

G

A

V

L

L

R

R

E

E

G

N

L

L

T

L

A

G

N

E

R

N

I

I

Q

K

Y

R

I

I

A

D

G

A

I

V

N

N

G

A

T

S

T

T

N

T

Y

F

I

I

L

L

S

T

E

K

M

M

R

S

D

E

R

-

G

G

L

K

D

T

F

L

A

D

T

D

A

A

L

I

K

E

A

E

A

A

Q

K

E

S

L

L

G

G

Y

I

A

L

E

E

A

E

D

D

P

P

T

S

F

K

D

D

I

I

E

D

G

G

V

I

D
|
D

A

A

A

Y

H

Y

K
|
K

A

A

T

K

I

I

M

L

S

H

A

W

I

V

A

S

F

Y

G

G

V

E

P

P

V

P

Q

E

F

E

D

E

R

E

A

-

Y

-

V

-

E

-

G

-

I

-

S

-

K

R

L

L

A

G

A

I

I

R

D

E

I

V

K

R

Y

D

A

A

E

R

E

-

L

-

G

-

Y

-

R

N

I

V

K

R

L

L

L

V

G

A

I

-

A

-

R

-

R

Q

T

V

D

S

K

K

G

G

I

-

E

K

L

I

R

S

V

V

H

K

P

P

T

R

L

K

I

L

P

S

E

S

K

D

R

N

L

P

L

L

A

L

N

-

V

V

E

E

G

G

A

V

M

Q

N

N

A

A

V

A

V

V

V

I

H

R

G

T

D

N

A

N

V

L

G

G

T

E

T

V

L

I

Y

L

Y

K

G

G

K

P

G

G

A
x
G

G

G

A

G

E

R

P

V

T
|
T

A

A

S

S

A

G

V

V

V

F

A

T

D

D

L

I

V

I

D

K

V

A

T

T

active site: D211 (= D204), K215 (= K208)
binding nadph dihydro-nicotinamide-adenine-dinucleotide phosphate: S114 (≠ A106), K116 (= K108), S141 (≠ A133), G295 (≠ A304), T300 (= T309)

Sites not aligning to the query:

binding nadph dihydro-nicotinamide-adenine-dinucleotide phosphate: 8, 10, 11, 12, 13, 39, 40, 57, 91, 92, 93

4xb2A Hyperthermophilic archaeal homoserine dehydrogenase mutant in complex with NADPH (see paper)
32% identity, 49% coverage: 103:321/443 of query aligns to 111:312/319 of 4xb2A

query
sites
4xb2A

V

V

T

T

A
x
S

N
|
N

K
|
K

A

P

L

P

L

I

A

A

V

N

H

Y

G

Y

T

D

E

E

I

L

F

M

E

N

A

L

A

A

R

K

A

E

N

N

G

N

V

A

M

G

V

I

A

F

F

F

E

E

A
x
S

A

T

V

V

A

M

G

A

G

G

I

T

P

P

I

I

K

G

A

V

L

L

R

R

E

E

G

N

L

L

T

L

A

G

N

E

R

N

I

I

Q

K

Y

R

I

I

A

D

G

A

I

V

N

N

G
x
A

T
x
S

T

T

N

T

Y

F

I

I

L

L

S

T

E

K

M

M

R

S

D

E

R

-

G

G

L

K

D

T

F

L

A

D

T

D

A

A

L

I

K

E

A

E

A

A

Q

K

E

S

L

L

G

G

Y

I

A

L

E

E

A

E

D

D

P

P

T

S

F

K

D
|
D

I

I

E

D

G

G

V

I

D
|
D

A

A

A

Y

H

Y

K
|
K

A

A

T

K

I

I

M

L

S

H

A

W

I

V

A

S

F

Y

G

G

V

E

P

P

V

P

Q

E

F

E

D

E

R

E

A

-

Y

-

V

-

E

-

G

-

I

-

S

-

K

R

L

L

A

G

A

I

I

R

D

E

I

V

K

R

Y

D

A

A

E

R

E

-

L

-

G

-

Y

-

R

N

I

V

K

R

L

L

L

V

G

A

I

-

A

-

R

-

R

Q

T

V

D

S

K

K

G

G

I

-

E

K

L

I

R

S

V

V

H

K

P

P

T

R

L

K

I

L

P

S

E

S

K

D

R

N

L

P

L

L

A

L

N

-

V

V

E

E

G

G

A

V

M

Q

N

N

A

A

V

A

V

V

V

I

H

R

G

T

D

N

A

N

V

L

G

G

T

E

T

V

L

I

Y

L

Y

K

G

G

K

P

G

G

A
x
G

G

G

A

G

E

R

P

V

T
|
T

A

A

S

S

A

G

V

V

V

F

A

T

D

D

L

I

V

I

D

K

V

A

T

T

active site: D211 (= D204), K215 (= K208)
binding l-homoserine: A171 (≠ G163), S172 (≠ T164), D206 (= D199), K215 (= K208)
binding nadph dihydro-nicotinamide-adenine-dinucleotide phosphate: S114 (≠ A106), N115 (= N107), K116 (= K108), S141 (≠ A133), G295 (≠ A304), T300 (= T309)

Sites not aligning to the query:

binding nadph dihydro-nicotinamide-adenine-dinucleotide phosphate: 8, 10, 11, 12, 13, 40, 91, 92, 93

3jsaA Homoserine dehydrogenase from thermoplasma volcanium complexed with NAD
28% identity, 52% coverage: 1:231/443 of query aligns to 1:239/321 of 3jsaA

query
sites
3jsaA

M

M

E

K

P

T

I

I

K

N

V

L

G

S

L

I

L

F

G
|
G

F
x
L

G
|
G

T
x
N

V
|
V

G

G

S

L

G

N

T

L

F

L

T

R

V

I

L

I

R

R

R

S

N

F

Q

N

E

E

-

N

-

R

-

L

-

G

-

L

-

K

-

F

-

N

-

V

-

F

-

V

-

A

-
x
D

-
x
S

I

L

K

H

R

S

R

Y

A

Y

G

N

R

E

G

R

I

I

E

D

V

I

A

G

R

K

I

V

A

I

V

S

R

Y

N

K

P

E

A

K

K

G

A

S

T

L

A

D

A

S

L

L

G

E

A

Y

D

E

A

S

P

I

S

S

V

A

-

S

-

E

A

A

L

L

T

A

D

R

D

D

F

F

N

D

A

I

V

V

D

D

D
x
A

P
x
T

S
x
P

I

-

D

-

I

-

V

-

A

A

E

S

M

A

I

D

G

G

G

K

T

K

G

E

V

L

A

A

R

-

D

-

L

F

V

Y

L

K

R

E

A

T

I

F

K

E

N

N

R

G

K

K

H

D

V

V

T

T

A
|
A

N
|
N

K

K

A

S

L

G

L

L

A

A

V

N

H

F

G

W

T

P

E

E

I

I

F

M

E

E

A

Y

A

A

R

R

A

S

N

N

G

N

V

R

M

R

V

I

A

R

F

Y

E

E

A
|
A

A

T

V

V

A

A

G

G

I

V

P

P

I

L

I

F

K

S

A

F

L

I

R

D

E

Y

G

S

L

V

T

L

A

P

N

S

R

R

I

I

Q

K

Y

K

I

F

A

R

G

G

I

I

I

V

N

S

G

L

T

T

T

I

N

N

Y

Y

I

F

L

I

S

R

E

E

M

L

R

A

D

N

R

K

G

-

L

R

D

E

F

F

A

D

T

D

A

V

L

L

K

S

A

E

A

A

Q

T

E

K

L

L

G

G

Y

I

A

V

E

N

A

Y

D

K

P

D

T

-

F

-

D

D

I

L

E

T

G

G

V

L

D
|
D

A

A

H

R

K
|
K

A

S

T

V

I

I

M

L

S

C

A

N

I

H

A

L

F

Y

G

G

V

S

P

S

V

Y

Q

R

F

L

D

S

R

D

A

V

Y

F

V

Y

E

E

G

G

I

I

active site: D212 (= D204), K216 (= K208)
binding nicotinamide-adenine-dinucleotide: G10 (= G10), L11 (≠ F11), G12 (= G12), N13 (≠ T13), V14 (= V14), D42 (vs. gap), S43 (vs. gap), A90 (≠ D73), T91 (≠ P74), P92 (≠ S75), A117 (= A106), N118 (= N107), A144 (= A133)

Sites not aligning to the query:

binding nicotinamide-adenine-dinucleotide: 308

3ingA Crystal structure of homoserine dehydrogenase (np_394635.1) from thermoplasma acidophilum at 1.95 a resolution
26% identity, 52% coverage: 2:233/443 of query aligns to 1:238/319 of 3ingA

query
sites
3ingA

E

K

P

E

I

I

K

R

V

I

G

I

L

L

L

M

G
|
G

F
x
T

G
|
G

T
x
N

V
|
V

G

G

S

-

G

-

T

-

F

L

T

N

V

V

L

L

R

R

R

I

N

I

Q

D

E

A

E

S

I

N

K

R

R

R

A

-

G

-

R

-

G

-

I

F

E

S

V

I

A

K

R

V

I

V

A

G

V

V

R

S

N
x
D

P
x
S

A

R

K

S

A

Y

T

A

A

S

A

G

L

R

G

N

A

L

D

D

A

I

P

S

S

S

V

I

A

I

L

S

T

N

D
x
K

D

E

F

K

N

T

A

G

V

R

V

I

D

S

D

D

P

R

S

A

I

F

-

S

-

G

-

P

-

E

D

D

I

L

V

M

A

G

E

E

-

A

-

D

-

L

M

L

I

V

G

D

G
x
C

T
|
T

G
x
P

V

A

A

S

R

R

D

D

-

G

-

V

-

R

-

E

-

Y

-

S

L

L

V

Y

L

R

R

M

A

A

I

F

K

E

N

S

R

G

K

M

H

N

V

V

T

T

A
|
A

N
|
N

K
|
K

A

S

L

G

L

L

A

A

V

N

H

K

G

W

T

H

E

D

I

I

F

M

E

D

A

S

A

A

R

N

A

Q

N

N

G

S

V

K

M

Y

V

I

A

R

F

Y

E

E

A
|
A

A

T

V

V

A

A

G

G

I

V

P

P

I

L

I

F

K

S

A

V

L

L

R

D

E

Y

G

S

L

I

T

L

A

P

N

S

R

K

I

V

Q

K

Y

R

I

F

A

R

G

G

I

I

I

V

N

S

G

S

T

T

T

I

N

N

Y

Y

I

V

L

I

S

R

E

N

M

M

R

A

D

N

R

-

G

G

L

R

D

S

F

L

A

R

T

D

A

V

L

V

K

D

A

D

A

A

Q

I

E

K

L

K

G

G

Y

I

A

A

E
|
E

A
x
S

D

N

P

P

T

Q

F

D

D

D

I

L

E

N

G

G

V

L

D
|
D

A

A

H

R

K
|
K

A

S

T

V

I

I

M

L

S

V

A

N

I

H

A

I

F

F

G

G

V

T

P

E

V

Y

Q

T

F

L

D

N

R

D

A

V

Y

E

V

Y

E

S

G

G

I

V

S

D

K

E

active site: D209 (= D204), K213 (= K208)
binding nadph dihydro-nicotinamide-adenine-dinucleotide phosphate: G9 (= G10), T10 (≠ F11), G11 (= G12), N12 (≠ T13), V13 (= V14), D38 (≠ N46), S39 (≠ P47), K57 (≠ D65), C85 (≠ G85), T86 (= T86), P87 (≠ G87), A112 (= A106), N113 (= N107), K114 (= K108), A139 (= A133), E198 (= E193), S199 (≠ A194)

Sites not aligning to the query:

binding nadph dihydro-nicotinamide-adenine-dinucleotide phosphate: 302, 305

O94671 Probable homoserine dehydrogenase; HDH; EC 1.1.1.3 from Schizosaccharomyces pombe (strain 972 / ATCC 24843) (Fission yeast) (see paper)
34% identity, 29% coverage: 95:222/443 of query aligns to 110:244/376 of O94671

query
sites
O94671

R

K

A

F

I

L

K

S

N

K

R

K

K

I

H

N

V

I

V

A

T

T

A

P

N

N

K

K

A

K

L

A

L

F

A

S

V

A

H

S

G

N

-

D

-

V

-

Y

T

Q

E

N

I

I

F

I

E

K

A

A

A

S

R

K

A

E

N

S

G

G

V

A

M

L

V

L

A

M

F

H

E

E

A

A

A

S

V

V

A

G

G

A

G

G

I

L

P

P

I

I

K

S

A

T

L

L

R

K

E

E

G

L

L

I

-

A

T

T

A

G

N

D

R

E

I

I

Q

I

Y

K

I

I

A

E

G

G

I

I

I

F

N

S

G

G

T

T

T

L

N

S

Y

Y

I

I

L

F

S

N

E

V

M

W

R

S

D

P

R

N

G

G

-

K

-

G

-

T

L

A

D
x
S

F

F

A

S

T

D

A

I

L

V

K

K

A

I

A

A

Q

K

E

Q

L

N

G

G

Y

Y

A

T

E

E

A

P

D

D

P

P

T

R

F

D

D

D

I

L

E

N

G

G

V

M

D

D

A

V

A

A

H

R

K

K

A

V

T

T

I

I

M

L

S

S

A

R

I

I

A

A

F

-

G

G

V

V

P

H

V

V

Q

E

S201 (≠ D178) modified: Phosphoserine

P31116 Homoserine dehydrogenase; HDH; EC 1.1.1.3 from Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast) (see paper)
29% identity, 49% coverage: 4:222/443 of query aligns to 6:236/359 of P31116

query
sites
P31116

I

V

K

N

V

V

G

A

L

V

L
x
I

G
|
G

F
x
A

G
|
G

T
x
V

V
|
V

G
|
G

S
|
S

G

A

T

F

F

L

T

D

V

Q

L

L

R

L

R

A

N

M

Q

K

E

S

E

T

I

I

K

T

R

Y

R

N

A

L

G

V

R

L

G

L

I

A

E

E

V

A

A

E

R

R

I

S

A

L

V

I

R

S

-

K

-

D

-

F

N

S

P

P

-

L

-

N

-

V

-

G

A

S

K

D

A

W

T

K

A

A

L

L

G

A

A

A

D

S

A

T

P

T

S

K

V

T

A

L

L

P

T

L

D

D

F

L

N

I

A

A

-

H

V

L

V

K

D

T

D

S

P

P

S

K

I

P

D

V

I

I

V

L

A

V

E

D

M

N

I
x
T

G

S

T

A

G

Y

V

I

A

A

R

-

D

G

L

F

V

Y

L

T

R

K

A

F

I

V

K

E

N

N

R

G

K

I

H

S

V

I

V

A

T

T

A

P

N

N

K
|
K

A

K

L

A

L

F

A

S

-

S

-

D

-

L

V

A

H

T

G

W

T

K

E

A

I

L

F

F

E

S

A

N

A

K

R

P

A

T

N

N

G

G

V

-

M

F

V

V

A

Y

F

H

E

E

A

A

A

T

V

V

A

G

G

A

G

G

I

L

P

P

I

I

K

S

A

F

L

L

R

R

E

E

G

I

L

I

-

Q

T

T

A

G

N

D

R

E

I

V

Q

E

Y

K

I

I

A

E

G

G

I

I

I

F

N

S

G

G

T

T

T

L

N

S

Y

Y

I

I

L

F

S

N

E

E

M

F

-

S

-

T

-

S

R

Q

D

A

R

N

G

D

L

V

D

K

F

F

A

S

T

D

A

V

L

V

K

K

A

V

A

A

Q

K

E

K

L

L

G

G

Y

Y

A

T

E
|
E

A

P

D

D

P

P

T

R

F

D

D

D

I

L

E

N

G

G

V

L

D
|
D

A

V

A

A

H

R

K
|
K

A

V

T

T

I

I

M

V

S

G

A

R

I

I

A

S

F

-

G

G

V

V

P

E

V

V

Q

E

11:18 (vs. 9:16, 63% identical) binding NADP(+)
T93 (≠ I83) binding NADP(+)
K117 (= K108) binding NADP(+)
E208 (= E193) binding substrate; mutation to D: Increases KM for aspartate-semialdehyde 48-fold and reduces kcat by 50%.; mutation E->L,Q: Loss of activity.
D219 (= D204) mutation to L: Reduces kcat 150-fold.
K223 (= K208) mutation to V: Loss of activity.

1tveA Homoserine dehydrogenase in complex with 4-(4-hydroxy-3- isopropylphenylthio)-2-isopropylphenol (see paper)
29% identity, 49% coverage: 4:222/443 of query aligns to 5:235/358 of 1tveA

query
sites
1tveA

I

V

K

N

V

V

G

A

L

V

L

I

G

G

F

A

G

G

T

V

V

V

G

G

S

S

G

A

T

F

F

L

T

D

V

Q

L

L

R

L

R

A

N

M

Q

K

E

S

E

T

I

I

K

T

R

Y

R

N

A

L

G

V

R

L

G

L

I

A

E

E

V

A

A

E

R

R

I

S

A

L

V

I

R

S

-

K

-

D

-

F

N

S

P

P

-

L

-

N

-

V

-

G

A

S

K

D

A

W

T

K

A

A

L

L

G

A

A

A

D

S

A

T

P

T

S

K

V

T

A

L

L

P

T

L

D

D

F

L

N

I

A

A

-

H

V

L

V

K

D

T

D

S

P

P

S

K

I

P

D

V

I

I

V

L

A

V

E

D

M

N

I

T

G
x
S

G

S

T

A

G

Y

V

I

A

A

R

-

D

G

L

F

V

Y

L

T

R

K

A

F

I

V

K

E

N

N

R

G

K

I

H

S

V

I

V

A

T

T

A

P

N

N

K
|
K

A

K

L

A

L

F

A

S

-

S

-

D

-

L

V

A

H

T

G

W

T

K

E

A

I

L

F

F

E

S

A

N

A

K

R

P

A

T

N

N

G

G

V

-

M

F

V

V

A

Y

F

H

E

E

A

A

A

T

V

V

A

G

G

A

G

G

I

L

P

P

I

I

K

S

A

F

L

L

R

R

E

E

G

I

L

I

-

Q

T

T

A

G

N

D

R

E

I

V

Q

E

Y

K

I

I