SitesBLAST

SitesBLAST – Find functional sites

SitesBLAST

Comparing WP_084544571.1 NCBI__GCF_000482785.1:WP_084544571.1 to proteins with known functional sites using BLASTp with E ≤ 0.001.

Or try Sites on a Tree, PaperBLAST, Conserved Domains, or compare to all protein structures

Found 20 (the maximum) hits to proteins with known functional sites (download)

P13009 Methionine synthase; 5-methyltetrahydrofolate--homocysteine methyltransferase; Methionine synthase, vitamin-B12-dependent; MS; EC 2.1.1.13 from Escherichia coli (strain K12) (see 5 papers)
62% identity, 98% coverage: 22:910/911 of query aligns to 341:1199/1227 of P13009

query
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P13009

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E694 (= E390) binding methylcob(III)alamin
GDVHD 756:760 (= GDVHD 459:463) binding methylcob(III)alamin
D757 (= D460) mutation to E: Decreases activity by about 70%.; mutation to N: Decreases activity by about 45%.
H759 (= H462) binding axial binding residue; mutation to G: Loss of catalytic activity.
S804 (= S507) binding methylcob(III)alamin
T808 (= T511) binding methylcob(III)alamin
S810 (= S513) mutation to A: Decreases activity by about 40%.
A860 (= A567) binding methylcob(III)alamin
D946 (= D653) binding S-adenosyl-L-methionine
R1134 (= R846) binding S-adenosyl-L-methionine
YY 1189:1190 (≠ YF 900:901) binding S-adenosyl-L-methionine

Sites not aligning to the query:

1 modified: Initiator methionine, Removed
247 binding Zn(2+)
310 binding Zn(2+); mutation C->A,S: Loss of zinc binding. Loss of catalytic activity.
311 binding Zn(2+); mutation C->A,S: Loss of zinc binding. Loss of catalytic activity.

Q99707 Methionine synthase; MS; 5-methyltetrahydrofolate--homocysteine methyltransferase; Cobalamin-dependent methionine synthase; Vitamin-B12 dependent methionine synthase; EC 2.1.1.13 from Homo sapiens (Human) (see 6 papers)
54% identity, 99% coverage: 8:910/911 of query aligns to 340:1237/1265 of Q99707

query
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Q99707

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L

L

F

F

G

G

Q

A

G

G

K

K

M

M

F

F

L

L

P

P

Q

Q

V

V

V

I

K

K

S

S

A

A

R

R

V

V

M

M

K

K

Q

K

A

A

V

V

A

G

H

H

L

L

I

I

P

P

F

F

I

M

E

E

E

K

E

E

K

R

R

E

Q

E

I

T

E

R

A

V

A

L

G

N

G

G

D

T

V

V

R

E

S

E

-

E

-

D

-

P

-

Y

K

Q

G

G

K

T

I

I

V

V

I

L

A

A

T

T

V

V

K

K

G

G

D

D

V

V

H

H

D

D

I

I

G

G

K

K

N

N

I

I

V

V

S

G

V

V

L

L

Q

G

C

C

N

N

F

F

E

R

V

V

V

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N

D

M

L

G

G

V

V

M

M

V

T

P

P

C

C

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D

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K

I

I

L

L

A

K

K

A

A

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D

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A

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I

I

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G

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L

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P

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L

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M

M

A

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Y

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V

A

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E

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M

M

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-

F

-

R

L

V

A

K

I

K

R

I

I

P

P

L

L

I

I

G

G

A

A

T

T

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S

R

K

V

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H

H

T

T

A

A

V

V

K

K

I

I

A

A

P

P

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Y

Y

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A

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V

V

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V

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D

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V

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L

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I

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x
D

H

H

A

Y

N

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L

K

K

A

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T

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P

R

L

Y

L

L

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P

L

L

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A

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K

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F

A

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M

D

D

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W

R

L

A

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A

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A

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-

H

P

P

V

V

K

K

P

P

K

T

F

F

L

I

G

G

R

T

R

Q

E

V

F

F

R

E

N
x
D

Y

Y

D

D

L

L

A

Q

E

K

L

L

A

V

R

D

Y

Y

I

I

D

D

W

W

G

K

P

P

F

F

Q

D

T

V

W

W

D

Q

L

L

H

R

G

G

-

K

-

Y

-

P

-

N

-

R

A

G

F

F

P

P

A

K

L

I

L

F

D

N

D

D

P

K

V

T

V

V

G

G

E

G

S

E

A

A

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R

K

K

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V

F

Y

A

D

D

D

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M

M

L

L

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N

K

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L

L

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I

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Q

K

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V

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F

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W

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A

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D

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L

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F

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G

L

L

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R

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Q

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A

A

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K
|
K

R

D

E

S

G

A

V

S

E

T

N

E

K

P

-

Y

C

C

L

L

A

S

D

D

Y

F

I

I

A

A

P

P

L

L

D

H

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S

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G

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I

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R

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D

Y

Y

I

L

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L

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F

A

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V

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-

A

A

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C

L

F

G

G

A

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D

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K

E

L

L

A

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A

Y

Y

E

E

A

D

H

G

D

D

Y

Y

S

S

A

S

I

I

M

M

V

V

K

K

A

A

L

L

A

G

D

D

R

R

L

L

A

A

E

E

A

A

F

F

A

A

E

E

A

E

M

L

H

H

E

E

R

R

V

V

R

R

K

R

D

E

L

L

W

W

G

A

Y

Y

A

C

P

G

D

S

E

E

A

Q

L

L

T

D

N

V

E

A

E

D

L

L

I

R

K

R

E

L

K

R

Y

Y

V

K

G

G

I

I

R

R

P

P

A

A

P

P

G

G

Y

Y

P

P

A

S

C

Q

P

P

R

D

H

H

E

T

V

E

K

K

R

L

E

T

M

M

F

W

A

R

A

L

L

A

D

D

-

I

A

E

T

Q

A

S

I

T

G

G

M

I

G

R

L

L

T

T

E

E

S

S

F

L

A

A

M

M

T

A

P

P

A

A

S

S

S

A

V

V

S

S

G

G

F

L

Y

Y

L

F

S

S

H

N

P

L

K

K

A

S

Q

K

Y

Y

F

F

N

A

V

V

G

G

E

K

I

I

G

S

D

K

E

D

Q

Q

GSR 382:384 (≠ GSK 48:50) binding (6S)-5,6,7,8-tetrahydrofolate
D449 (= D115) binding (6S)-5,6,7,8-tetrahydrofolate
N470 (= N136) binding (6S)-5,6,7,8-tetrahydrofolate
D537 (= D203) binding (6S)-5,6,7,8-tetrahydrofolate
N579 (= N245) binding (6S)-5,6,7,8-tetrahydrofolate
R585 (= R251) binding (6S)-5,6,7,8-tetrahydrofolate
R591 (= R257) binding (6S)-5,6,7,8-tetrahydrofolate
D919 (≠ A600) to G: in dbSNP:rs1805087
D963 (≠ N642) mutation to E: Decreases binding to MTRR; when associated with N-1071.
K1071 (= K746) mutation to N: Decreases binding to MTRR; when associated with E-963.

Sites not aligning to the query:

61 natural variant: R -> K
255 C → Y: in dbSNP:rs1140598

3ivaA Structure of the b12-dependent methionine synthase (meth) c-teminal half with adohcy bound (see paper)
57% identity, 61% coverage: 351:910/911 of query aligns to 9:549/576 of 3ivaA

query
sites
3ivaA

V

V

E

N

Q

K

R

R

L

L

S

E

H

Y

A

S

L

L

V

V

H

K

G

G

I

I

T

T

N

E

F

F

I

I

T

E

E

Q

D

D

T

T

E

E

A

A

R

R

A

Q

A

-

I

-

A

-

R

Q

G

A

G

T

R

R

P

P

I

C

E

E

V

V

I

I

E

E

G

G

P

P

L

L

M

M

A

D

G

G

M

M

N

N

V

V

G

G

D

D

L

L

F

F

G

G

Q

E

G

G

K

K

M

M

F

F

L

L

P

P

Q

Q

V

V

K

K

S

S

A

A

R

R

V

V

M

M

K

K

Q

Q

A

A

V

V

A

A

H

Y

L

L

I

E

P

P

F

F

I

I

E

E

E

A

E

S

K

K

R

E

Q

Q

I

-

E

-

A

-

G

-

D

-

V

C

R

K

S

T

K

N

G

G

K

K

I

M

V

V

I

I

A

A

T

T

V

V

K

K

G

G

D
|
D

V

V

H
|
H

D

D

I

I

G
|
G

K

K

N

N

I

I

V
|
V

S

G

V

V

L

L

Q

Q

C

C

N

N

F

Y

E

E

V

I

V

V

N

D

M

L

G

G

V

V

M

M

V

V

P

P

C

A

S

E

E

K

I

I

L

L

A

R

K

T

A

A

K

K

V

E

E

V

G

N

A

A

D

D

I

L

I

I

G
|
G

L
|
L

S
|
S

G

G

L
|
L

I
|
I

T
|
T

P

P

S
|
S

L

L

E

D

E

E

M

M

A

V

Y

N

V

V

A

A

T

K

E

E

M

M

Q

E

R

R

D

Q

D

G

F

F

F

-

R

-

V

-

K

-

K

T

I

I

P

P

L

L

I

I

G
|
G

A

A

T

T

S

S

R

K

V

A

H

H

T

T

A

A

V

V

K

K

I

I

A

E

P

Q

H

N

Y

Y

D

S

G

G

P

P

V

T

V

V

Y

Y

V

V

P
x
Q

D
x
N

A

A

S

S

R

R

S

T

V

V

S

G

V

V

A

V

Q

A

S

A

L

L

S

S

D

D

E

T

G

Q

A

R

A

D

R

D

Y

F

I

V

S

A

E

R

L

T

E

R

A

K

E

E

Y

Y

D

E

R

T

V

V

R

R

T

I

A

Q

H

H

A

G

N

R

K

K

A

P

-

R

T

T

P

P

L

P

L

V

P

T

L

L

A

E

E

A

A

A

R

R

A

D

H

N

K

D

P

F

A

A

I

F

D

D

W

W

R

Q

A

A

A

Y

A

T

P

P

V

P

K

V

P

A

K

H

F

R

L

L

G

G

R

V

R

Q

E

E

F

V

R

E

N

A

Y

-

D

S

L

I

A

E

E

T

L

L

A

R

R

N

Y

Y

I

I

D

D

W

W

G

T

P

P

F

F

Q

M

T
|
T

W

W

D

S

L

L

H

A

G

G

A

K

F

Y

P

P

A

R

L

I

L

L

D

E

D

D

P

E

V

V

G

G

E

V

S

E

A

A

R

Q

K

R

V

L

F

F

A

K

D

D

G

A

Q

N

A

D

M

M

L

L

K

D

K

K

L

L

I

S

D

A

G

E

R

K

Q

T

L

L

N

N

A

P

S

R

A

G

V

V

G

G

F

L

W

F

P

P

A

A

N

N

S

R

D

V

G

G

A

-

E

D

T

D

I

I

T

E

L

I

Y

Y

T

R

D

D

D

E

D

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A

-

R

-

D

-

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R

A

T

H

H

V

V

L

I

F

N

R

V

W

S

K

H

N

H

L

L

R

R

Q

Q

T

T

A

E

K

K

R

T

E

-

G

G

V

F

E

A

N

N

K

Y

C

C

L

L

A

A

D

D

Y

F

I

V

A

A

P

P

L

K

D

L

S

S

G

G

V

K

R

A

D

D

Y

Y

I

I

G

G

V

A

F

F

A

A

V

V

T

T

A

G

G

G

L

L

G

E

A

E

D

D

K

A

L

L

A

A

E

D

R

A

Y

F

E

E

A

A

A

Q

H

H

D

D

Y

Y

S

N

A

K

I

I

M

M

V

V

K

K

A

A

L

L

A

A

D
|
D

R

R

L

L

A

A

E
|
E

A

A

F

F

A

A

E

E

A

Y

M

L

H

H

E

E

R

R

V

V

R

R

K

K

D

V

L

Y

W

W

G

G

Y

Y

A

A

P

P

D

N

E

E

A

N

L

L

T

S

N

N

E

E

L

L

I

I

K

R

E

E

K

N

Y

Y

V

Q

G

G

I

I

R
|
R

P
|
P

A
|
A

P

P

G
|
G

Y
|
Y

P

P

A
|
A

C

C

P

P

R

E

H
|
H

E

T

V

E

K

K

R

A

E

T

M

I

F

W

A

E

A

L

L

L

D

E

A

V

T

E

A

K

-

H

I

T

G

G

M

M

G

K

L

L

T

T

E

E

S

S

F

F

A
|
A

M
|
M

T

W

P

P

A
x
G

S

A

S

S

V
|
V

S
|
S

G

G

F

W

Y

Y

L

F

S

S

H

H

P

P

K

D

A

S

Q

K

Y
|
Y

F

Y

N

A

V

V

G

A

E

Q

I

I

G

Q

D

R

E

D

Q

Q

active site: D107 (= D460), H109 (= H462), S160 (= S513)
binding cobalamin: H109 (= H462), G112 (= G465), V116 (= V469), G152 (= G505), L153 (= L506), S154 (= S507), L156 (= L509), I157 (= I510), T158 (= T511), G183 (= G540), G184 (= G541), Q208 (≠ P565), N209 (≠ D566), T303 (= T660), D443 (= D805), A486 (= A848), G488 (= G850), Y489 (= Y851), H495 (= H857), A520 (= A881), M521 (= M882), G524 (≠ A885), V527 (= V888), S528 (= S889)
binding s-adenosyl-l-homocysteine: E447 (= E809), R484 (= R846), P485 (= P847), Y489 (= Y851), A491 (= A853), Y539 (= Y900)

3bulA E. Coli i690c/g743c meth c-terminal fragment (649-1227) (see paper)
57% identity, 61% coverage: 351:910/911 of query aligns to 9:549/577 of 3bulA

query
sites
3bulA

V

V

E

N

Q

K

R

R

L

L

S

E

H

Y

A

S

L

L

V

V

H

K

G

G

I

I

T

T

N

E

F

F

I

I

T

E

E

Q

D

D

T

T

E

E

A

A

R

R

A

Q

A

-

I

-

A

-

R

Q

G

A

G

T

R

R

P

P

I

C

E

E

V

V

I

I

E

E

G

G

P

P

L

L

M

M

A

D

G

G

M

M

N

N

V

V

G

G

D

D

L

L

F

F

G

G

Q

E

G

G

K

K

M

M

F

F

L

L

P

P

Q

Q

V

V

K

K

S

S

A

A

R

R

V

V

M

M

K

K

Q

Q

A

A

V

V

A

A

H

Y

L

L

I

E

P

P

F

F

I

I

E

E

E

A

E

S

K

K

R

E

Q

Q

I

-

E

-

A

-

G

-

D

-

V

C

R

K

S

T

K

N

G

G

K

K

I

M

V

V

I

I

A

A

T

T

V

V

K

K

G

G

D
|
D

V

V

H
|
H

D

D

I

I

G

G

K

K

N

N

I

I

V
|
V

S

G

V

V

L

L

Q

Q

C

C

N

N

F

Y

E

E

V

I

V

V

N

D

M

L

G

G

V

V

M

M

V

V

P

P

C

A

S

E

E

K

I

I

L

L

A

R

K

T

A

A

K

K

V

E

E

V

G

N

A

A

D

D

I

L

I

I

G
|
G

L
|
L

S
|
S

G

G

L
|
L

I
|
I

T
|
T

P

P

S
|
S

L

L

E

D

E

E

M

M

A

V

Y

N

V

V

A

A

T

K

E

E

M

M

Q

E

R

R

D

Q

D

G

F

F

F

-

R

-

V

-

K

-

K

T

I

I

P

P

L

L

I

I

G
|
G

A

A

T

T

S

S

R

K

V

A

H

H

T

T

A

A

V

V

K

K

I

I

A

E

P

Q

H

N

Y

Y

D

S

G

G

P

P

V

T

V

V

Y

Y

V

V

P
x
Q

D
x
N

A
|
A

S

S

R

R

S
x
T

V

V

S

G

V

V

A

V

Q

A

S

A

L

L

S

S

D

D

E

T

G

Q

A

R

A

D

R

D

Y

F

I

V

S

A

E

R

L

T

E

R

A

K

E

E

Y

Y

D

E

R

T

V

V

R

R

T

I

A

Q

H

H

A

G

N

R

K

K

A

P

-

R

T

T

P

P

L

P

L

V

P

T

L

L

A

E

E

A

A

A

R

R

A

D

H

N

K

D

P

F

A

A

I

F

D

D

W

W

R

Q

A

A

A

Y

A

T

P

P

V

P

K

V

P

A

K

H

F

R

L

L

G

G

R

V

R

Q

E

E

F

V

R

E

N

A

Y

-

D

S

L

I

A

E

E

T

L

L

A

R

R

N

Y

Y

I

I

D

D

W

W

G

T

P

P

F

F

Q
x
M

T

T

W

W

D

S

L

L

H

A

G

G

A

K

F

Y

P

P

A

R

L

I

L

L

D

E

D

D

P

E

V

V

G

G

E

V

S

E

A

A

R

Q

K

R

V

L

F

F

A

K

D

D

G

A

Q

N

A

D

M

M

L

L

K

D

K

K

L

L

I

S

D

A

G

E

R

K

Q

T

L

L

N

N

A

P

S

R

A

G

V

V

G

G

F

L

W

F

P

P

A

A

N

N

S

R

D

V

G

G

A

-

E

D

T

D

I

I

T

E

L

I

Y

Y

T

R

D

D

D

E

D

T

A

-

R

-

D

-

E

R

A

T

H

H

V

V

L

I

F

N

R

V

W

S

K

H

N

H

L

L

R

R

Q

Q

T

T

A

E

K

K

R

T

E

-

G

G

V

F

E

A

N

N

K

Y

C

C

L

L

A

A

D

D

Y

F

I

V

A

A

P

P

L

K

D

L

S

S

G

G

V

K

R

A

D

D

Y

Y

I

I

G

G

V

A

F

F

A

A

V

V

T

T

A

G

G

G

L

L

G

E

A

E

D

D

K

A

L

L

A

A

E

D

R

A

Y

F

E

E

A

A

A

Q

H

H

D

D

Y

Y

S

N

A

K

I

I

M

M

V

V

K

K

A

A

L

L

A

A

D
|
D

R

R

L

L

A

A

E

E

A

A

F

F

A

A

E

E

A

Y

M

L

H

H

E

E

R

R

V

V

R

R

K

K

D

V

L

Y

W

W

G

G

Y

Y

A

A

P

P

D

N

E

E

A

N

L

L

T

S

N

N

E

E

L

L

I

I

K

R

E

E

K

N

Y

Y

V

Q

G

G

I

I

R

R

P

P

A
|
A

P
|
P

G
|
G

Y
|
Y

P

P

A

A

C

C

P

P

R

E

H
|
H

E

T

V

E

K
|
K

R

A

E

T

M

I

F

W

A

E

A

L

L

L

D

E

A

V

T

E

A

K

-

H

I

T

G

G

M

M

G

K

L

L

T

T

E

E

S

S

F

F

A

A

M
|
M

T

W

P

P

A
x
G

S

A

S

S

V
|
V

S
|
S

G

G

F

W

Y

Y

L

F

S

S

H

H

P

P

K

D

A

S

Q

K

Y

Y

F

Y

N

A

V

V

G

A

E

Q

I

I

G

Q

D

R

E

D

Q

Q

active site: D107 (= D460), H109 (= H462), S160 (= S513)
binding cobalamin: H109 (= H462), V116 (= V469), G152 (= G505), L153 (= L506), S154 (= S507), L156 (= L509), I157 (= I510), T158 (= T511), G183 (= G540), G184 (= G541), Q208 (≠ P565), N209 (≠ D566), A210 (= A567), T213 (≠ S570), M302 (≠ Q659), D443 (= D805), A486 (= A848), P487 (= P849), G488 (= G850), Y489 (= Y851), H495 (= H857), K498 (= K860), M521 (= M882), G524 (≠ A885), V527 (= V888), S528 (= S889)

3k13C Structure of the pterin-binding domain metr of 5- methyltetrahydrofolate-homocysteine methyltransferase from bacteroides thetaiotaomicron
66% identity, 32% coverage: 37:329/911 of query aligns to 4:286/287 of 3k13C

query
sites
3k13C

F

F

V

V

N

N

V

I

G

G

E
|
E

R

R

T

C

N

N

V

V

T

A

G
|
G

S

S

K
x
R

M

K

F

F

A

L

R

R

L

L

I

V

L

N

N

E

G

K

E

K

Y

Y

D

D

Q

E

A

A

L

L

A

S

V

I

A

A

R

R

Q

Q

V

V

E

E

N

D

G

G

A

A

Q

L

I

V

I

I

D

D

V

V

N

N

M

M

D

D

E

D

A

G

M

L

L

L

D

D

S

A

K

R

A

T

A

E

M

M

T

T

R

T

F

F

L

L

N

N

L

L

I

I

A

M

S

S

E

E

P

P

D

E

I

I

A

A

R

R

V

V

P

P

I

V

M

M

I

I

D

D

S

S

K

K

W

W

E

E

V

V

I

I

E

E

A

A

G

G

L

L

K

K

C

C

V

L

Q

Q

G

G

K

K

S

S

I

I

V

V

N
|
N

S

S

I

I

S

S

L

L

K

K

E

E

G

G

E

E

A

E

N

V

F

F

I

L

H

E

Q

H

A

A

K

R

L

I

C

I

R

K

R

Q

Y

Y

G

G

A

A

V

T

I

V

V

V

M

M

A

A

F

F

D

D

E

E

K

K

G

G

Q

Q

A

A

D

D

T

T

F

A

A

A

R

R

K

K

T

I

E

E

I

V

C

C

A

E

R

R

A

A

Y

Y

K

R

V

L

L

L

T

V

E

D

K

K

V

V

G

G

F

F

A

N

P

P

E

H

D

D

I

I

F

F

D
|
D

P

P

N

N

I

V

F

L

A

A

I

V

A

A

T

T

G

G

I

I

E

E

H

H

D

N

N

N

Y

Y

A

A

V

V

D

D

F

F

I

I

E

E

A

A

C

T

R

G

W

W

I

I

R

R

A

K

N

N

L

L

P

P

H

G

A

A

R

H

I

V

S

S

G

G

G
|
G

V

V

S
|
S

N
|
N

V

L

S

S

F

F

S

S

F

F

R
|
R

G

G

N

N

E

N

P

Y

V

I

R
|
R

E

E

A

A

I

M

H

H

T

A

V

V

F

F

L

L

Y

Y

H

H

A

A

I

I

R

Q

A

Q

G

G

M

M

T

D

M

M

G

G

I
|
I

V

V

N

N

A

P

G

G

Q

S

L

V

G

-

V

L

Y

Y

A

S

D

D

L

I

D

P

P

A

E

D

L

T

R

L

E

E

R

K

V

I

E

E

D

D

V

V

L

L

N

N

R

R

V

R

P

P

K

D

Q

-

A

-

E

-

G

-

E

-

P

-

K

-

T

-

A

A

T

A

E

E

R

R

L

L

L

I

E

E

I

L

A

A

E

E

R

A

F

L

K

K

binding n-[4-({[(6s)-2-amino-4-hydroxy-5-methyl-5,6,7,8-tetrahydropteridin-6-yl]methyl}amino)benzoyl]-l-glutamic acid: E9 (= E42), G15 (= G48), R17 (≠ K50), N103 (= N136), D170 (= D203), G209 (= G242), S211 (= S244), N212 (= N245), R218 (= R251), R224 (= R257), I244 (= I277)

4cczA Crystal structure of human 5-methyltetrahydrofolate-homocysteine methyltransferase, the homocysteine and folate binding domains
59% identity, 34% coverage: 13:326/911 of query aligns to 305:611/611 of 4cczA

query
sites
4cczA

V

V

P

P

R

A

R

T

S

A

R

F

P

E

-

G

-

H

L

M

R

L

L

L

S

S

G

G

L

L

E

E

A

P

L

F

S

R

I

I

D

G

D

P

D

Y

T

T

L

N

F

F

V

V

N

N

V

I

G

G

E
|
E

R

R

T

C

N

N

V

V

T

A

G
|
G

S

S

K
x
R

M

K

F

F

A

A

R

K

L

L

I

I

L

M

N

A

G

G

E

N

Y

Y

D

E

Q

E

A

A

L

L

A

C

V

V

A

A

R

K

Q

V

Q

Q

V

V

E

E

N

M

G

G

A

A

Q

Q

I

V

I

L

D

D

V

V

N

N

M

M

D

D

E

D

A

G

M

M

L

L

D

D

S

G

K

P

A

S

A

A

M

M

T

T

R

R

F

F

L

C

N

N

L

L

I

I

A

A

S

S

E

E

P

P

D

D

I

I

A

A

R

K

V

V

P

P

I

L

M

C

I

I

D

D

S

S

K

N

W

F

E

A

V

V

I

I

E

E

A

A

G

G

L

L

K

K

C

C

V

C

Q

Q

G

G

K

K

S

C

I

I

V

V

N
|
N

S

S

I

I

S

S

L

L

K

K

E

E

G

G

E

E

A

D

N

D

F

F

I

L

H

E

Q

K

A

A

K

R

L

K

C

I

R

K

Y

Y

G

G

A

A

V

M

I

V

V

V

M
|
M

A

A

F

F

D

D

E

E

K

E

G

G

Q

Q

A

A

D

T

T

E

F

T

A

D

R

T

K

K

T

I

E

R

I

V

C

C

A

T

R

R

A

A

Y

Y

K

H

V

L

L

L

T

V

E

K

K

K

V

L

G

G

F

F

A

N

P

P

E

N

D

D

I

I

F

F

D
|
D

P

P

N

N

I

I

F

L

A

T

I

I

A

G

T

T

G

G

I

M

E

E

H

H

D

N

N

L

Y

Y

A

A

V

I

D

N

F

F

I

I

E

H

A

A

C

T

R

K

W

V

I

I

R

K

A

E

N

T

L

L

P

P

H

G

A

A

R

R

I

I

S

S

G

G

G
|
G

V

L

S
|
S

N
|
N

V

L

S

S

F
|
F

S

S

F

F

R
|
R

G

G

N

M

E

E

P

A

V

I

R
|
R

E

E

A

A

I

M

H

H

T

G

V

V

F

F

L

L

Y

Y

H

H

A

A

I

I

R

K

A

S

G

G

M

M

T

D

M

M

G

G

I

I

V

V

N

N

A

A

G

G

Q

N

L

L

G

P

V

V

Y

Y

A

D

D

D

L

I

D

H

P

K

E

E

L

L

R

L

E

Q

R

L

V

C

E

E

D

D

V

L

V

I

L

W

N

N

R

K

V

D

P

P

K

E

Q

-

A

-

E

-

G

-

E

-

P

-

K

-

T

-

A

A

T

T

E

E

R

K

L

L

E

R

I

Y

A

A

E

Q

binding (6s)-5,6,7,8-tetrahydrofolate: E336 (= E42), G342 (= G48), R344 (≠ K50), N430 (= N136), M458 (= M164), D497 (= D203), G536 (= G242), S538 (= S244), N539 (= N245), F542 (= F248), R545 (= R251), R551 (= R257)

1bmtA How a protein binds b12: a 3.O angstrom x-ray structure of the b12- binding domains of methionine synthase (see paper)
63% identity, 28% coverage: 351:602/911 of query aligns to 9:245/246 of 1bmtA

query
sites
1bmtA

V

V

E

N

Q

K

R

R

L

L

S

E

H

Y

A

S

L

L

V

V

H

K

G

G

I

I

T

T

N

E

F

F

I

I

T

E

E

Q

D

D

T

T

E

E

A

A

R

R

A

Q

A

-

I

-

A

-

R

Q

G

A

G

T

R

R

P

P

I

I

E

E

V

V

I

I

E
|
E

G

G

P

P

L

L

M
|
M

A

D

G

G

M
|
M

N

N

V

V

G
|
G

D

D

L

L

F

F

G

G

Q

E

G

G

K

K

M

M

F

F

L
|
L

P

P

Q

Q

V
|
V

V

V

K

K

S

S

A

A

R

R

V

V

M

M

K

K

Q

Q

A

A

V

V

A

A

H

Y

L

L

I

E

P

P

F

F

I

I

E

E

E

A

E

S

K

K

R

E

Q

Q

I

-

E

-

A

-

G

-

D

-

V

G

R

K

S

T

K

N

G

G

K

K

I

M

V

V

I

I

A

A

T

T

V

V

K

K

G

G

D
|
D

V
|
V

H
|
H

D
|
D

I
|
I

G

G

K

K

N

N

I
|
I

V

V

S

G

V

V

L

L

Q

Q

C

C

N

N

F

Y

E

E

V

I

V

V

N

D

M

L

G

G

V

V

M

M

V

V

P

P

C

A

S

E

E

K

I

I

L

L

A

R

K

T

A

A

K

K

V

E

E

V

G

N

A

A

D

D

I

L

I

I

G
|
G

L
|
L

S
|
S

G

G

L
|
L

I
|
I

T
|
T

P

P

S
|
S

L

L

E

D

E

E

M

M

A

V

Y

N

V

V

A

A

T

K

E

E

M

M

Q

E

R

R

D

Q

D

G

F

F

F

-

R

-

V

-

K

-

K

T

I

I

P

P

L

L

I

I

G
|
G

A
|
A

T

T

S

S

R

K

V

A

H

H

T

T

A

A

V

V

K

K

I

I

A

E

P

Q

H

N

Y

Y

D

S

G

G

P

P

V

T

V

V

Y

Y

V
|
V

P

Q

D
x
N

A
|
A

S

S

R

R

S

T

V

V

S

G

V

V

A

V

Q

A

S

A

L

L

S

S

D

D

E

T

G

Q

A

R

A

D

R

D

Y

F

I

V

S

A

E

R

L

T

E

R

A

K

E

E

Y

Y

D

E

R

T

V

V

R

R

T

I

A

Q

H

H

A

G

active site: D107 (= D460), H109 (= H462), S160 (= S513)
binding co-methylcobalamin: E44 (= E390), M48 (= M394), M51 (= M397), G55 (= G401), L65 (= L411), V68 (= V414), D107 (= D460), V108 (= V461), H109 (= H462), D110 (= D463), I111 (= I464), I115 (= I468), G152 (= G505), L153 (= L506), S154 (= S507), L156 (= L509), I157 (= I510), T158 (= T511), G183 (= G540), G184 (= G541), A185 (= A542), V207 (= V564), N209 (≠ D566), A210 (= A567)

6bdyA Crystal structure of the meth reactivation domain bound to sinefungin (see paper)
52% identity, 33% coverage: 607:910/911 of query aligns to 1:299/326 of 6bdyA

query
sites
6bdyA

T

T

P

P

L

P

L

V

P

T

L

L

A

E

E

A

A

A

R

R

A

D

H

N

K

D

P

F

A

A

I

F

D

D

W

W

R

Q

A

A

A

Y

A

T

P

P

V

P

K

V

P

A

K

H

F

R

L

L

G

G

R

V

R

Q

E

E

F

V

R

E

N

A

Y

-

D

S

L

I

A

E

E

T

L

L

A

R

R

N

Y

Y

I

I

D
|
D

W

W

G

T

P

P

F

F

Q

M

T

T

W

W

D

S

L

L

H

A

G

G

A

K

F

Y

P

P

A

R

L

I

L

L

D

E

D

D

P

E

V

V

G

G

E

V

S

E

A

A

R

Q

K

R

V

L

F

F

A

K

D

D

G

A

Q

N

A

D

M

M

L

L

K

D

K

K

L

L

I

S

D

A

G

E

R

K

Q

T

L

L

N

N

A

P

S

R

A

G

V

V

G

G

F

L

W

F

P

P

A

A

N

N

S

R

D

V

G

G

A

-

E

D

T

D

I

I

T

E

L

I

Y

Y

T

R

D

D

D

E

D

T

A

-

R

-

D

-

E

R

A

T

H

H

V

V

L

I

F

N

R

V

W

S

K

H

N

H

L

L

R

R

Q

Q

T

T

A

E

K

K

R

T

E

-

G

G

V

F

E

A

N

N

K

Y

C

C

L

L

A

A

D

D

Y

F

I

V

A

A

P

P

L

K

D

L

S

S

G

G

V

K

R

A

D

D

Y

Y

I

I

G

G

V

A

F

F

A

A

V

V

T

T

A

G

G

G

L

L

G

E

A

E

D

D

K

A

L

L

A

A

E

D

R

A

Y

F

E

E

A

A

A

Q

H

H

D

D

Y

Y

S

N

A

K

I

I

M

M

V

V

K

K

A

A

L

L

A

A

D

D

R

R

L

L

A

A

E

E

A

A

F

F

A

A

E

E

A

Y

M

L

H

H

E

E

R

R

V

V

R

R

K

K

D

V

L

Y

W

W

G

G

Y

Y

A

A

P

P

D

N

E

E

A

N

L

L

T

S

N

N

E

E

L

L

I

I

K

R

E

E

K

N

Y

Y

V

Q

G

G

I

I

R
|
R

P
|
P

A
|
A

P

P

G

G

Y
|
Y

P
|
P

A
|
A

C

C

P

P

R

E

H

H

E

T

V

E

K

K

R

A

E

T

M

I

F

W

A

E

A

L

L

L

D

E

A

V

T

E

A

K

-

H

I

T

G

G

M

M

G

K

L

L

T

T

E

E

S

S

F

F

A

A

M

M

T

W

P

P

A

G

S

A

S

S

V

V

S

S

G

G

F

W

Y

Y

L

F

S

S

H

H

P

P

K

D

A

S

Q

K

Y
|
Y

F

Y

N

A

V

V

G

A

E

Q

I

I

G

Q

D

R

E

D

Q

Q

binding sinefungin: D46 (= D653), R234 (= R846), P235 (= P847), A236 (= A848), Y239 (= Y851), P240 (= P852), A241 (= A853), Y289 (= Y900)

1mskA Methionine synthase (activation domain) (see paper)
52% identity, 33% coverage: 607:910/911 of query aligns to 1:299/327 of 1mskA

query
sites
1mskA

T

T

P

P

L

P

L

V

P

T

L

L

A

E

E

A

A

A

R

R

A

D

H

N

K

D

P

F

A

A

I

F

D

D

W

W

R

Q

A

A

A

Y

A

T

P

P

V

P

K

V

P

A

K

H

F

R

L

L

G

G

R

V

R

Q

E

E

F

V

R

E

N

A

Y

-

D

S

L

I

A

E

E

T

L

L

A

R

R

N

Y

Y

I

I

D
|
D

W

W

G

T

P

P

F

F

Q

M

T

T

W

W

D

S

L

L

H

A

G

G

A

K

F

Y

P

P

A

R

L

I

L

L

D

E

D

D

P

E

V

V

G

G

E

V

S

E

A

A

R

Q

K

R

V

L

F

F

A

K

D

D

G

A

Q

N

A

D

M

M

L

L

K

D

K

K

L

L

I

S

D

A

G

E

R

K

Q

T

L

L

N

N

A

P

S

R

A

G

V

V

G

G

F

L

W

F

P

P

A

A

N

N

S

R

D

V

G

G

A

-

E

D

T

D

I

I

T

E

L

I

Y

Y

T

R

D

D

D

E

D

T

A

-

R

-

D

-

E

R

A

T

H

H

V

V

L

I

F

N

R

V

W

S

K

H

N

H

L

L

R

R

Q

Q

T

T

A

E

K

K

R

T

E

-

G

G

V

F

E

A

N

N

K

Y

C

C

L

L

A

A

D

D

Y

F

I

V

A

A

P

P

L

K

D

L

S

S

G

G

V

K

R

A

D

D

Y

Y

I

I

G

G

V

A

F

F

A

A

V

V

T

T

A

G

G

G

L

L

G

E

A

E

D

D

K

A

L

L

A

A

E

D

R

A

Y

F

E

E

A

A

A

Q

H

H

D

D

Y

Y

S

N

A

K

I

I

M

M

V

V

K

K

A

A

L

L

A

A

D

D

R

R

L

L

A

A

E

E

A

A

F

F

A

A

E

E

A

Y

M

L

H

H

E

E

R

R

V

V

R

R

K

K

D

V

L

Y

W

W

G

G

Y

Y

A

A

P

P

D

N

E

E

A

N

L

L

T

S

N

N

E

E

L

L

I

I

K

R

E

E

K

N

Y

Y

V

Q

G

G

I

I

R
|
R

P
|
P

A

A

P

P

G

G

Y
|
Y

P

P

A
|
A

C

C

P

P

R

E

H

H

E

T

V

E

K

K

R

A

E

T

M

I

F

W

A

E

A

L

L

L

D

E

A

V

T

E

A

K

-

H

I

T

G

G

M

M

G

K

L

L

T

T

E

E

S

S

F

F

A

A

M

M

T

W

P

P

A

G

S

A

S

S

V

V

S

S

G

G

F

W

Y

Y

L

F

S

S

H

H

P

P

K

D

A

S

Q

K

Y
|
Y

F

Y

N

A

V

V

G

A

E

Q

I

I

G

Q

D

R

E

D

Q

Q

binding s-adenosylmethionine: D46 (= D653), R234 (= R846), P235 (= P847), Y239 (= Y851), A241 (= A853), Y289 (= Y900)

8g3hA Structure of cobalamin-dependent methionine synthase (meth) in a resting state (see paper)
35% identity, 60% coverage: 27:577/911 of query aligns to 322:832/841 of 8g3hA

query
sites
8g3hA

E

Q

A

A

L

V

S

P

I

L

D

R

D
x
Q

D

E

T
|
T

L
x
S

F

L

V

L

N

L

V

V

G

G

E

E

R

R

T

L

N

N

V

A

T

T

G

G

S

S

K

K

M

R

F

F

A

R

R

E

L

L

I

L

L

F

N

A

G

G

E

D

Y

L

D

E

Q

G

A

I

L

L

A

A

V

L

A

A

R

Q

Q

E

Q

Q

V

V

E

A

N

E

G

G

A

A

Q

H

I

V

I

L

D

D

V

L

N

S

M

V

D

A

E

W

A

T

M

G

L

R

D

D

S

E

K

L

A

E

A

D

M

M

T

K