SitesBLAST

SitesBLAST – Find functional sites

SitesBLAST

Comparing GFF980 FitnessBrowser__Phaeo:GFF980 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)

Q1LK00 Tryptophan 2,3-dioxygenase; TDO; Tryptamin 2,3-dioxygenase; Tryptophan oxygenase; TO; TRPO; Tryptophan pyrrolase; Tryptophanase; EC 1.13.11.11 from Cupriavidus metallidurans (strain ATCC 43123 / DSM 2839 / NBRC 102507 / CH34) (Ralstonia metallidurans) (see paper)
63% identity, 96% coverage: 11:277/277 of query aligns to 32:299/299 of Q1LK00

query
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Q1LK00

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F68 (= F47) mutation to A: Abolishes catalytic activity.
Y130 (= Y109) mutation to F: 15-fold increase in catalytic activity.
R134 (= R113) mutation to A: Abolishes catalytic activity.
T271 (= T249) mutation to A: Abolishes catalytic activity.

2noxB Crystal structure of tryptophan 2,3-dioxygenase from ralstonia metallidurans (see paper)
62% identity, 96% coverage: 11:277/277 of query aligns to 3:266/266 of 2noxB

query
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2noxB

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binding protoporphyrin ix containing fe: F39 (= F47), H43 (= H51), T46 (≠ S54), W90 (= W98), L93 (= L101), S112 (= S120), G113 (= G121), F114 (= F122), Y119 (= Y127), R120 (= R128), H228 (= H235), V232 (= V239), E242 (≠ T249), Y246 (= Y257), L247 (= L258)

Q8PDA8 Tryptophan 2,3-dioxygenase; TDO; Tryptamin 2,3-dioxygenase; Tryptophan oxygenase; TO; TRPO; Tryptophan pyrrolase; Tryptophanase; EC 1.13.11.11 from Xanthomonas campestris pv. campestris (strain ATCC 33913 / DSM 3586 / NCPPB 528 / LMG 568 / P 25) (see 2 papers)
47% identity, 96% coverage: 11:277/277 of query aligns to 13:282/298 of Q8PDA8

query
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Q8PDA8

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FIIQH 51:55 (= FIIQH 47:51) binding
H55 (= H51) mutation to A: Decrease in catalytic efficiency using L-tryptophan, 5-fluoro-D/L-tryptophan, 6-fluoro-D/L-tryptophan, 5-methyl-D/L-tryptophan and 6-methyl-D/L-tryptophan as substrate.; mutation to S: Decrease in catalytic efficiency using L-tryptophan, 5-fluoro-D/L-tryptophan, 6-fluoro-D/L-tryptophan, 5-methyl-D/L-tryptophan and 6-methyl-D/L-tryptophan as substrate.
Y113 (= Y109) binding
R117 (= R113) binding
H240 (= H235) binding axial binding residue
T254 (= T249) binding

2nw9A Crystal structure of tryptophan 2,3-dioxygenase (tdo) from xanthomonas campestris in complex with ferrous heme and 6-fluoro-tryptophan. Northeast structural genomics target xcr13 (see paper)
48% identity, 94% coverage: 18:277/277 of query aligns to 1:263/265 of 2nw9A

query
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2nw9A

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binding 6-fluoro-l-tryptophan: F32 (= F47), H36 (= H51), Y94 (= Y109), R98 (= R113), L101 (= L116), S104 (= S119), G234 (= G248), T235 (= T249)
binding protoporphyrin ix containing fe: F32 (= F47), H36 (= H51), S39 (= S54), W83 (= W98), L86 (= L101), G106 (= G121), F107 (= F122), Y112 (= Y127), R113 (= R128), H221 (= H235), V225 (= V239), I229 (= I243), G234 (= G248), G236 (= G250), S238 (≠ T252)

7p46A Crystal structure of xanthomonas campestris tryptophan 2,3-dioxygenase (tdo) (see paper)
47% identity, 96% coverage: 11:277/277 of query aligns to 9:278/281 of 7p46A

query
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7p46A

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W
|
W

D

S

V

V

L

L

R

E

T

T

M

L

T

T

P

P

S

S

D

E

Y
|
Y

S

M

A

G

F

F

R
|
R

D

D

E

V

L

L

G

G

Q

P

S
|
S

G
|
G

F
|
F

Q

Q

S

S

H

L

Q

Q

Y
|
Y

R
|
R

Q

Y

I

I

E

E

F

F

M

L

L

L

G

G

N

N

R

K

N

N

K

P

A

Q

M

M

L

L

R

Q

P

V

H

F

A

A

H

Y

R

D

P

P

D

A

V

G

L

Q

A

A

L

R

L

L

E

R

D

E

E

V

L

L

S

E

Q

A

P

P

S

S

L

L

Y

Y

D

E

V

E

A

F

L

L

K

R

T

Y

L

L

G

A

Q

-

R

R

F

F

D

G

-

H

-

A

L

I

P

P

K

Q

E

Q

V

Y

L

Q

N

A

R

R

N

D

L

W

S

T

E

A

A

A

Y

H

T

V

P

A

H

D

P

D

A

T

V

L

E

R

A

P

A

V

W

F

S

E

E

R

V

I

Y

Y

R

E

N

N

T

T

E

D

A

R

H

Y

W

W

D

R

L

E

Y
|
Y

E
x
S

L

L

A

C

E
|
E

K

D

L

L

V

V

D
|
D

F

V

E

E

D

T

Y

Q

F

F

R

Q

R

L

W

W

R

R

F

F

N

R

H
|
H

V

M

T

R

T

T

V
|
V

E

M

R

R

V

V

I

I

G

G

F

F

K

K

R

R

G
|
G

T
|
T

G
|
G

G

G

T
x
S

G

S

G

G

V

V

S

G

Y

F

L

L

K

Q

R

Q

M

A

L

L

E

A

V

L

E

T

L

F

F

F

P

P

E

E

L

L

W

F

H

D

L

V

R

R

T

T

A

S

L

V

binding protoporphyrin ix containing fe: S51 (≠ H51), S54 (= S54), W98 (= W98), S120 (= S120), G121 (= G121), F122 (= F122), Y127 (= Y127), R128 (= R128), H236 (= H235), V240 (= V239), G249 (= G248), G251 (= G250), S253 (≠ T252)
binding (2S)-2-amino-4-(2-aminophenyl)-4-oxobutanoic acid: F47 (= F47), S51 (≠ H51), Y109 (= Y109), R113 (= R113), S119 (= S119), G249 (= G248), T250 (= T249)
binding tryptophan: K82 (= K82), A85 (= A85), Y216 (= Y215), S217 (≠ E216), E220 (= E219), D224 (= D223)

1yw0A Crystal structure of the tryptophan 2,3-dioxygenase from xanthomonas campestris. Northeast structural genomics target xcr13.
43% identity, 93% coverage: 21:277/277 of query aligns to 1:241/243 of 1yw0A

query
sites
1yw0A

S

T

Y

Y

G

G

D

G

Y

Y

L

L

S

R

L

L

D

D

L

Q

L

L

N

S

A
|
A

Q
|
Q

K
x
Q

T

P

W

L

T

S

N

E

T

P

-

A

-

H

H

H

D

D

E

E

M

M

L

L

F

F

I

I

Q

Q

H

H

Q

Q

T

T

S

S

E

E

L

L

W

W

M

L

R

K

L

L

A

L

I

A

H

H

E

E

L

L

T

R

A

A

R

I

S

V

R

H

L

L

L

Q

A

R

N

D

K

E

P

V

H

W

E

Q

A

C

F

R

K

K

M

V

L

L

A

A

R

R

V

S

A

K

R

Q

I

V

F

L

E

R

Q

Q

L

L

N

T

S

E

A

Q

W

W

D

S

V

V

L

L

R

E

T

T

M

L

T

T

P

P

S

S

D

E

Y

Y

S

M

A

G

F

F

R

R

D

D

E

V

L

L

G

-

Q

-

S

-

G

G

F

F

Q

Q

S

S

H

L

Q

Q

Y

Y

R

R

Q

Y

I

I

E

E

F

F

M

L

L

L

G

G

N

N

R

K

N

N

K

P

A

Q

M

M

L

L

R

Q

P

V

H

F

A

A

H

Y

R

D

P

P

D

A

V

G

L

Q

A

A

L

R

L

L

E

R

D

E

E

V

L

L

S

E

Q

A

P

P

S

S

L

L

Y

Y

D

E

V

E

A

F

L

L

K

R

T

Y

L

L

G

A

Q

-

R

R

F

F

D

G

-

H

-

A

L

I

P

P

K

Q

E

Q

V

Y

L

Q

N

A

R

R

N

D

L

W

S

T

E

A

A

A

Y

H

T

V

P

A

H

D

P

D

A

T

V

L

E

R

A

P

A

V

W

F

S

E

E

R

V

I

Y

Y

R

E

N

N

T

T

E

D

A

R

H

Y

W

W

D

R

L

E

Y

Y

E

S

L

L

A

C

E

E

K

D

L

L

V

V

D

D

F

V

E

E

D

T

Y

Q

F

F

R

Q

R

L

W

W

R

R

F

F

N

R

H

H

V

M

T

R

T

T

V

V

E

M

R

R

V

V

I

I

G

G

F

F

K

A

R

-

G

-

T

-

G

-

T

-

G

-

V

-

S

-

Y

-

L

-

K

-

R

-

M

-

L

L

E

A

V

L

E

T

L

F

F

F

P

P

E

E

L

L

W

F

H

D

L

V

R

R

T

T

A

S

L

V

binding magnesium ion: A14 (= A34), Q15 (= Q35), Q16 (≠ K36)

5ti9C Crystal structure of human tdo in complex with trp and dioxygen, northeast structural genomics consortium target hr6161 (see paper)
31% identity, 93% coverage: 20:277/277 of query aligns to 1:307/326 of 5ti9C

query
sites
5ti9C

M

L

S

I

Y

Y

G

G

D

N

Y

Y

L

L

S

H

L

L

D

E

L

K

L

V

L

L

N

N

A

A

Q

Q

K

E

T

L

W

Q

T

S

N

E

T

T

-

K

-

G

-

N

-

K

-

I

H

H

D

D

E

E

M

H

L

L

F
|
F

I

I

Q

T

H
|
H

Q

Q

T

A

S
x
Y

E

E

L

L

W

W

M

F

R

K

L

Q

A

I

I

L

H

W

E

E

L

L

T

D

A

S

A

V

R

R

S

E

R

I

L

F

L

Q

A

N

N

G

K

H

P

V

H
x
R

E

D

A
x
E

F

R

K

N

M

M

L

L

A

K

R

V

V

V

A

S

R

R

-

M

-

H

-

R

-

V

-

S

-

V

I

I

F

L

E

K

Q

L

L

L

N

V

S

Q

A

Q

W

F

D

S

V

I

L
|
L

R

E

T

T

M

M

T

T

P

A

S

L

D

D

Y

F

S

N

A

D

F

F

R
|
R

D

E

E

Y

L
|
L

G

S

Q

P

S
x
A

S
|
S

G
|
G

F
|
F

Q

Q

S

S

H

L

Q

Q

Y
x
F

R
|
R

Q

L

I

L

E

E

F

N

M

K

L

I

G

G

-

V

-

L

-

Q

N

N

R

R

-

D

-

N

-

F

-

K

-

G

-

E

N

N

K

E

A

L

M

L

L

L

R

K

P

S

H

E

A

Q

H

E

R

K

P

T

D

-

V

L

L

L

A

E

L

L

L

V

E

E

D

A

E
x
W

L

L

S

E

Q
x
R

-
x
T

P
|
P

S

G

L

L

Y

E

D

P

V

H

A

G

L

F

K

N

T

F

L

W

G

G

Q

K

-

L

-

E

-

K

-

N

-

I

-

T

-

R

-

G

-

L

-

E

-

F

-

I

R

R

F

F

D

Q

L

K

P

Q

K

K

E

E

V

V

L

L

N

L

R

S

N

L

L

F

S

D

E

E

A

K

Y

R

T

H

P

E

H

H

P

L

A

L

V

S

E

K

A

G

A

E

W

R

S

R

E

L

V

S

Y

Y

R

R

N

A

T

L

E

Q

A

G

H

A

W

L

D

M

L
x
I

Y

Y

-

F

-

Y

-

R

-

E

-

P

-

R

-
x
F

-

Q

-

V

-
x
P

-

F

E

Q

L

L

A

L

E

T

K

S

L

L

V

M

D

D

F

I

E

D

D

S

Y

L

F

M

R

T

R

K

W
|
W

R

R

F

Y

N

N

H
|
H

V

V

T

C

T

M

V
|
V

E

H

R

R

V
x
M

I
x
L

G

G

F

S

K

K

R

A

G
|
G

T
|
T

G
|
G

G

G

T
x
S

G

S

G

G

V

Y

S

H

Y

Y

L
|
L

K

R

R

S

M

T

L

V

E

S

-

D

-

R

V

Y

E

K

L

V

F

F

P

V

E

D

L

L

W

F

H

N

L

L

R

S

T

T

A

Y

L

L

binding protoporphyrin ix containing fe: H37 (= H51), Y40 (≠ S54), L93 (= L101), S112 (= S120), G113 (= G121), F114 (= F122), F119 (≠ Y127), R120 (= R128), W259 (= W231), H263 (= H235), V267 (= V239), M270 (≠ V242), G276 (= G248), G278 (= G250), S280 (≠ T252), L286 (= L258)
binding N'-Formylkynurenine: F33 (= F47), H37 (= H51), R105 (= R113), L108 (= L116), A111 (≠ S119), S112 (= S120), G113 (= G121), L271 (≠ I243), G276 (= G248), T277 (= T249)
binding tryptophan: R64 (≠ H78), E66 (≠ A80), W159 (≠ E158), R162 (≠ Q161), T163 (vs. gap), P164 (= P162), I230 (≠ L214), F239 (vs. gap), P242 (vs. gap)

6pyzC Crystal structure of human tryptophan 2,3-dioxygenase in complex with pf-06840003 in active site (see paper)
29% identity, 93% coverage: 20:277/277 of query aligns to 2:314/333 of 6pyzC

query
sites
6pyzC

M

L

S

I

Y
|
Y

G

G

D

N

Y
|
Y

L

L

S

H

L

L

D

E

L

K

L

V

L

L

N

N

A

A

Q

Q

K

E

T

L

W

Q

T

S

N

E

T

T

-

K

-

G

-

N

-

K

-

I

H

H

D

D

E

E

M

H

L

L

F
|
F

I

I

Q

T

H
|
H

Q

Q

T

A

S
x
Y

E

E

L

L

W

W

M

F

R

K

L

Q

A

I

I

L

H

W

E

E

L

L

T

D

A

S

A

V

R

R

S

E

R

I

L

F

L

Q

A

N

N

G

K

H

P

V

H
x
R

E

D

A
x
E

F

R

K

N

M

M

L

L

A

K

R

V

V

V

A

S

R

R

-

M

-

H

-

R

-

V

-

S

-

V

I

I

F

L

E

K

Q

L

L

L

N

V

S

Q

A

Q

W

F

D

S

V

I

L
|
L

R

E

T

T

M

M

T

T

P

A

S

L

D

D

Y

F

S

N

A

D

F

F

R

R

D

E

E

Y

L

L

G

S

Q

P

S
x
A

S
|
S

G
|
G

F
|
F

Q

Q

S

S

H

L

Q

Q

Y
x
F

R
|
R

Q

L

I

L

E

E

F

N

M

K

L

I

-

G

-

V

-

L

-

Q

-

N

-

M

-

R

-

V

-

P

-

Y

-

H

-

Y

-

R

-

D

-

N

-

F

-

K

G

G

N

E

R

E

N

N

K

E

A

L

M

L

L

L

R

K

P

S

H

E

A

Q

H

E

R

K

P

T

D

-

V

L

L

L

A

E

L

L

L

V

E

E

D

A

E
x
W

L

L

S

E

Q
x
R

-
x
T

P
|
P

S

G

L

L

Y

E

D

P

V

H

A

G

L

F

K

N

T

F

L

W

G

G

Q

K

-

L

-

E

-

K

-

N

-

I

-

T

-

R

-

G

-

L

-

E

-

A

R

E

F

F

D

Q

L

K

P

Q

K

K

E

E

V

V

L

L

N

L

R

S

N

L

L

F

S

D

E

E

A

K

Y

R

T

H

P

E

H

H

P

L

A

L

V

S

E

K

A

G

A

E

W

R

S

R

E

L

V

S

Y

Y

R

R

N

A

T

L

E

Q

A

G

H

A

W

L

D

M

L

I

Y

Y

-

F

-

Y

-

R

-

E

-

P

-

R

-
x
F

-

Q

-

V

-

P

-

F

E

Q

L

L

A

L

E

T

K

S

L

L

V

M

D

D

F

I

E

D

D

S

Y

L

F

M

R

T

R

K

W

W

R

R

F

Y

N

N

H
|
H

V

V

T

C

T
x
M

V
|
V

E

H

R

R

V
x
M

I

L

G

G

F

S

K

K

R

A

G
|
G

T
|
T

G
|
G

G

G

T
x
S

G

S

G

G

V

Y

S

H

Y
|
Y

L
|
L

K

R

R

S

M

T

L

V

E

S

-

D

-

R

V

Y

E

K

L

V

F

F

P

V

E

D

L

L

W

F

H

N

L

L

R

S

T

T

A

Y

L

L

binding (3S)-3-(5-fluoro-1H-indol-3-yl)pyrrolidine-2,5-dione: Y4 (= Y22), Y7 (= Y25), F34 (= F47), H38 (= H51), A112 (≠ S119), S113 (= S120), T284 (= T249)
binding protoporphyrin ix containing fe: H38 (= H51), Y41 (≠ S54), L94 (= L101), G114 (= G121), F115 (= F122), F120 (≠ Y127), R121 (= R128), H270 (= H235), M273 (≠ T238), V274 (= V239), M277 (≠ V242), G283 (= G248), G285 (= G250), S287 (≠ T252), Y292 (= Y257), L293 (= L258)
binding alpha-methyl-L-tryptophan: R65 (≠ H78), E67 (≠ A80), W167 (≠ E158), R170 (≠ Q161), T171 (vs. gap), P172 (= P162), F246 (vs. gap)

6a4iD Crystal structure of human tdo inhibitor complex
30% identity, 82% coverage: 20:246/277 of query aligns to 1:250/290 of 6a4iD

query
sites
6a4iD

M

L

S

I

Y
|
Y

G

G

D

N

Y
|
Y

L

L

S

H

L

L

D

E

L

K

L

V

L

L

N

N

A

A

Q

Q

K

E

T

L

W

Q

T

S

N

E

T

T

-

K

-

G

-

N

-

K

-

I

H

H

D

D

E

E

M

H

L

L

F
|
F

I

I

Q

T

H
|
H

Q

Q

T

A

S
x
Y

E

E

L

L

W

W

M

F

R

K

L

Q

A

I

I

L

H

W

E

E

L

L

T

D

A

S

A

V

R

R

S

E

R

I

L

F

L

Q

A

N

N

G

K

H

P

V

H
x
R

E

D

A

E

F

R

K

N

M

M

L

L

A

K

R

V

V

V

A

S

R

R

-

M

-

H

-

R

-

V

-

S

-

V

I

I

F

L

E

K

Q

L

L

L

N

V

S

Q

A

Q

W

F

D

S

V

I

L

L

R

E

T

T

M

M

T

T

P

A

S

L

D

D

Y
x
F

S

N

A

D

F

F

R

R

D

E

E

Y

L

L

G

S

Q

P

S
x
A

S
|
S

G
|
G

F
|
F

Q

Q

S

S

H

L

Q

Q

Y
x
F

R

R

Q

L

I

L

E

E

-

N

-

K

-

I

-

G

F

V

M

L

L

K

G

G

N

E

R

E

N

N

K

E

A

L

M

L

L

L

R

K

P

S

H

E

A

Q

H

E

R

K

P

T

D

-

V

L

L

L

A

E

L

L

L

V

E

E

D

A

E
x
W

L

L

S

E

Q
x
R

-
x
T

P
|
P

S

G

L

L

Y

E

D

P

V

H

A

G

L

F

K

N

T

F

L

W

G

G

Q

K

-

L

-

E

-

V

-

L

-

S

R

L

F

F

D

D

L

E

P

K

K

R

E

H

V

E

L

H

N

L

R

L

N

S

L

K

S

G

E

E

A

R

Y

R

T

L

P

S

H

Y

P

R

A

A

V

L

E

Q

A

G

A

A

W

L

S

M

E
x
I

V

Y

Y

F

R

Y

N

R

T

E

E

E

A

P

H

R

W
x
F

D

Q

L

V

-

P

Y

F

E

Q

L

L

A

L

E

T

K

S

L

L

V

M

D

D

F

I

E

D

D

S

Y

L

F

M

R

T

R

K

W

W

R

R

F

Y

N

N

H
|
H

V

V

T

C

T

M

V
|
V

E

H

R

R

V
x
M

I

L

G

G

F

S

K

K

binding 1-(6-chloro-1H-indazol-4-yl)cyclohexan-1-ol: Y3 (= Y22), Y6 (= Y25), F33 (= F47), H37 (= H51), A111 (≠ S119)
binding protoporphyrin ix containing fe: F33 (= F47), H37 (= H51), Y40 (≠ S54), F101 (≠ Y109), S112 (= S120), G113 (= G121), F114 (= F122), F119 (≠ Y127), H239 (= H235), V243 (= V239), M246 (≠ V242)
binding tryptophan: R64 (≠ H78), W153 (≠ E158), R156 (≠ Q161), T157 (vs. gap), P158 (= P162), I206 (≠ E203), F215 (≠ W212)

Sites not aligning to the query:

binding protoporphyrin ix containing fe: 254

6a4iB Crystal structure of human tdo inhibitor complex
28% identity, 93% coverage: 20:277/277 of query aligns to 1:295/309 of 6a4iB

query
sites
6a4iB

M

L

S

I

Y
|
Y

G

G

D

N

Y
|
Y

L

L

S

H

L

L

D

E

L

K

L

V

L

L

N

N

A

A

Q

Q

K

E

T

L

W

Q

T

S

N

E

T

T

-

K

-

G

-

N

-

K

-

I

H

H

D

D

E

E

M

H

L

L

F
|
F

I

I

Q

T

H
|
H

Q

Q

T

A

S
x
Y

E

E

L

L

W

W

M

F

R

K

L

Q

A

I

I

L

H

W

E

E

L

L

T

D

A

S

A

V

R

R

S

E

R

I

L

F

L

Q

A

N

N

G

K

H

P

V

H
x
R

E

D

A
x
E

F

R

K

N

M

M

L

L

A

K

R

V

V

V

A

S

R

R

-

M

-

H

-

R

-

V

-

S

-

V

I

I

F

L

E

K

Q

L

L

L

N

V

S

Q

A

Q

W

F

D

S

V

I

L
|
L

R

E

T

T

M

M

T

T

P

A

S

L

D

D

Y

F

S

N

A

D

F

F

R

R

D

E

E

Y

L
|
L

G

S

Q

P

S
x
A

S
|
S

G
|
G

F
|
F

Q

Q

S

S

H

L

Q

Q

Y
x
F

R
|
R

Q

L

I

L

E

E

-

N

-

K

-

I

-

G

F

V

M

L

L

K

G

G

N

E

R

E

N

N

K

E

A

L

M

L

L

L

R

K

P

S

H

E

A

Q

H

E

R

K

P

T

D

-

V

L

L

L

A

E

L

L

L

V

E

E

D

A

E
x
W

L

L

S

E

Q
x
R

-
x
T

P
|
P

S

G

L

L

Y

E

D

P

V

H

A

G

L

F

K

N

T

F

L

W

G

G

Q

K

-

L

-

E

-

K

-

N

-

I

-

T

-

R

-

G

-

L

-

E

-

F

-

Q

-

V

-

A

R

E

F

F

D

Q

L

K

P

Q

K

K

E

E

V

V

L

L

N

L

R

S

N

L

L

F

S

D

E

E

A

K

Y

R

T

H

P

E

H

H

P

L

A

L

V

S

E

K

A

G

A

E

W

R

S

R

E

L

V

S

Y

Y

R

R

N

A

T

L

E

Q

A

G

H

A

W

L

D

M

L

I

Y

Y

-

F

-

Y

-

R

-

E

-

P

-

R

-

F

-

Q

-

V

-
x
P

-

F

E

Q

L

L

A

L

E

T

K

S

L

L

V

M

D

D

F

I

E

D

D

S

Y

L

F

M

R

T

R

K

W
|
W

R

R

F

Y

N

N

H
|
H

V

V

T

C

T

M

V
|
V

E

H

R

R

V

M

I

L

G

G

F

-

K

-

R

-

G

-

T

-

G

-

T

-

G

S

G

G

V

Y

S

H

Y

Y

L
|
L

K

R

R

S

M

T

L

V

E

S

-

D

-

R

V

Y

E

K

L

V

F

F

P

V

E

D

L

L

W

F

H

N

L

L

R

S

T

T

A

Y

L

L

binding 1-(6-chloro-1H-indazol-4-yl)cyclohexan-1-ol: Y3 (= Y22), Y6 (= Y25), F33 (= F47), H37 (= H51), L108 (= L116), A111 (≠ S119)
binding protoporphyrin ix containing fe: F33 (= F47), H37 (= H51), Y40 (≠ S54), L93 (= L101), S112 (= S120), G113 (= G121), F114 (= F122), F119 (≠ Y127), R120 (= R128), W255 (= W231), H259 (= H235), V263 (= V239), L274 (= L258)
binding tryptophan: R64 (≠ H78), E66 (≠ A80), W153 (≠ E158), R156 (≠ Q161), T157 (vs. gap), P158 (= P162), P238 (vs. gap)

P20351 Tryptophan 2,3-dioxygenase; TDO; Protein vermilion; Tryptamin 2,3-dioxygenase; Tryptophan oxygenase; TO; TRPO; Tryptophan pyrrolase; Tryptophanase; EC 1.13.11.11 from Drosophila melanogaster (Fruit fly) (see paper)
38% identity, 55% coverage: 1:153/277 of query aligns to 1:168/379 of P20351

query
sites
P20351

M

M

S

S

T

C

P

P

Y

Y

-

A

-

G

-

N

-

G

-

N

D

D

P

H

A

D

K

D

E

S

G

A

A

V

Q

P

M

L

S

T

F

T

D

E

G

V

R

G

M

K

S

I

Y

Y

G

G

D

E

Y

Y

L

L

S

M

L

L

D

D

L

K

L

L

N

D

A

A

Q

Q

K

C

T

M

W

L

T

S

N

E

-

E

-

D

-

K

-

R

-

P

T

V

H

H

D

D

E

E

M

H

L

L

F

F

I

I

Q

T

H

H

Q

Q

T

A

S

Y

E

E

L

L

W

W

M

F

R

K

L

Q

A

I

I

I

H

F

E

E

L

F

T

D

A

S

A

I

R

R

S

D

R

M

L

L

L

D

A

A

-

E

-

V

-

I

-

D

-

E

N

T

K

K

P

T

H

L

E

E

A

I

F

V

K

K

M

R

L

L

A

N

R

R

V

V

A

V

R

L

I

I

F

L

E

K

Q

L

L

L

N

V

S

D

A

Q

W

V

D

P

V

I

L

L

R

E

T

T

M

M

T

T

P

P

S

L

D
|
D

Y

F

S

M

A

D

F

F

R

R

D

K

E

Y

L

L

G

A

Q

P

S

A

S

S

G

G

F

F

Q

Q

S

S

H

L

Q

Q

Y

F

R

R

Q

L

I

I

E

E

F

N

M

K

L

L

G

G

N

V

R

L

N

T

K

E

A

Q

M

R

L

V

R

R

P

Y

H

N

A

Q

H

K

R

Y

P

S

D

D

V

V

L

F

A

S

D123 (= D108) mutation to A: Strongly reduced enzyme activity.

Sites not aligning to the query:

236 Y→F: Strongly reduced enzyme activity.
309 R→A: Strongly reduced enzyme activity.
312 binding axial binding residue
335 Y→F: Strongly reduced enzyme activity.

6a4iA Crystal structure of human tdo inhibitor complex
27% identity, 93% coverage: 20:277/277 of query aligns to 1:313/322 of 6a4iA

query
sites
6a4iA

M

L

S

I

Y
|
Y

G

G

D

N

Y
|
Y

L

L

S

H

L

L

D

E

L

K

L

V

L

L

N

N

A

A

Q

Q

K

E

T

L

W

Q

T

S

N

E

T

T

-

K

-

G

-

N

-

K

-

I

H

H

D

D

E

E

M

H

L

L

F
|
F

I

I

Q

T

H
|
H

Q

Q

T

A

S
x
Y

E

E

L

L

W

W

M

F

R

K

L

Q

A

I

I

L

H

W

E

E

L

L

T

D

A

S

A

V

R

R

S

E

R

I

L

F

L

Q

A

N

N

G

K

H

P

V

H
x
R

E

D

A

E

F

R

K

N

M

M

L

L

A

K

R

V

V

V

A

S

R

R

-

M

-

H

-

R

-

V

-

S

-

V

I

I

F

L

E

K

Q

L

L

L

N

V

S

Q

A

Q

W

F

D

S

V

I

L
|
L

R

E

T

T

M

M

T

T

P

A

S

L

D

D

Y
x
F

S

N

A

D

F

F

R

R

D

E

E

Y

L

L

G

S

Q

P

S
x
A

S
|
S

G
|
G

F
|
F

Q

Q

S

S

H

L

Q

Q

Y
x
F

R

R

Q

L

I

L

E

E

F

N

M

K

L

I

-

G

-

V

-

L

-

Q

-

N

-

M

-

N

-

F

-

K

G

G

N

E

R

E

N

N

K

E

A

L

M

L

L

L

R

K

P

S

H

E

A

Q

H

E

R

K

P

T

D

-

V

L

L

L

A

E

L

L

L

V

E

E

D

A

E
x
W

L

L

S

E

Q
x
R

-
x
T

P
|
P

S

G

L

L

Y

E

D

P

V

H

A

G

L

F

K

N

T

F

L

W

G

G

Q

K

-

L

-

E

-

K

-

N

-

I

-

T

-

R

-

G

-

L

-

E

-

F

-

I

-

R

-

I

-

Q

-

A

-

E

-

K

-

E

-

Q

-

V

-

A

R

E

F

F

D

Q

L

K

P

Q

K

K

E

E

V

V

L

L

N

L

R

S

N

L

L

F

S

D

E

E

A

K

Y

R

T

H

P

E

H

H

P

L

A

L

V

S

E

K

A

G

A

E

W

R

S

R

E

L

V

S

Y

Y

R

R

N

A

T

L

E

Q

A

G

H

A

W

L

D

M

L
x
I

Y

Y

-

F

-

Y

-

R

-

E

-

P

-

R

-
x
F

-

Q

-

V

-
x
P

-

F

E

Q

L

L

A

L

E

T

K

S

L

L

V

M

D

D

F

I

E

D

D

S

Y

L

F

M

R

T

R

K

W
|
W

R

R

F

Y

N

N

H
|
H

V

V

T

C

T
x
M

V
|
V

E

H

R

R

V
x
M

I

L

G

G

F

-

K

-

R

-

G

-

T

-

G

S

G

G

T

S

G

S

G

G

V

Y

S

H

Y

Y

L
|
L

K

R

R

S

M

T

L

V

E

S

-

D

-

R

V

Y

E

K

L

V

F

F

P

V

E

D

L

L

W

F

H

N

L

L

R

S

T

T

A

Y

L

L

binding 1-(6-chloro-1H-indazol-4-yl)cyclohexan-1-ol: Y3 (= Y22), Y6 (= Y25), F33 (= F47), H37 (= H51), A111 (≠ S119)
binding protoporphyrin ix containing fe: F33 (= F47), H37 (= H51), Y40 (≠ S54), L93 (= L101), F101 (≠ Y109), S112 (= S120), G113 (= G121), F114 (= F122), F119 (≠ Y127), W270 (= W231), H274 (= H235), M277 (≠ T238), V278 (= V239), M281 (≠ V242), L292 (= L258)
binding tryptophan: R64 (≠ H78), W158 (≠ E158), R161 (≠ Q161), T162 (vs. gap), P163 (= P162), I241 (≠ L214), F250 (vs. gap), P253 (vs. gap)

4hkaA Crystal structure of drosophila melanogaster tryptophan 2,3- dioxygenase in complex with heme (see paper)
41% identity, 48% coverage: 22:153/277 of query aligns to 4:145/345 of 4hkaA

query
sites
4hkaA

Y

Y

G

G

D

E

Y

Y

L

L

S

M

L

L

D

D

L

K

L

L

N

D

A

A

Q

Q

K

C

T

M

W

L

T

S

N

E

-

E

-

D

-

K

-

R

-

P

T

V

H

H

D

D

E

E

M

H

L

L

F

F

I

I

Q

T

H
|
H

Q

Q

T

A

S
x
Y

E

E

L

L

W

W

M
x
F

R

K

L

Q

A

I

I

I

H

F

E

E

L

F

T

D

A

S

A

I

R

R

S

D

R

M

L

L

L

D

A

A

-

E

-

V

-

I

-

D

-

E

N

T

K

K

P

T

H

L

E

E

A

I

F

V

K

K

M

R

L

L

A

N

R

R

V

V

A

V

R

L

I

I

F

L

E

K

Q

L

L

L

N

V

S

D

A

Q

W

V

D

P

V

I

L
|
L

R

E

T

T

M

M

T

T

P

P

S

L

D

D

Y
x
F

S

M

A

D

F

F

R

R

D

K

E

Y

L

L

G

A

Q

P

S

A

S

S

G

G

F
|
F

Q
|
Q

S

S

H

L

Q

Q

Y
x
F

R

R

Q

L

I

I

E

E

F

N

M

K

L

L

G

G

N

V

R

L

N

T

K

E

A

Q

M

R

L

V

R

R

P
x
Y

H

N

A

Q

H

K

R

Y

P

S

D

D

V

V

L

F

A

S

binding protoporphyrin ix containing fe: H38 (= H51), Y41 (≠ S54), F45 (≠ M58), L93 (= L101), F101 (≠ Y109), F114 (= F122), Q115 (= Q123), F119 (≠ Y127), Y136 (≠ P144)

Sites not aligning to the query:

binding protoporphyrin ix containing fe: 285, 289, 293, 312, 313

8qv7B Crystal structure of human tdo with alpha-methyl-l-tryptophan
29% identity, 81% coverage: 20:244/277 of query aligns to 1:272/310 of 8qv7B

query
sites
8qv7B

M

L

S

I

Y

Y

G

G

D

N

Y

Y

L

L

S

H

L

L

D

E

L

K

L

V

L

L

N

N

A

A

Q

Q

K

E

T

L

W

Q

T

S

N

E

T

T

-

K

-

G

-

N

-

K

-

I

H

H

D

D

E

E

M

H

L

L

F

F

I

I

Q

T

H

H

Q

Q

T

A

S

Y

E

E

L

L

W

W

M

F

R

K

L

Q

A

I

I

L

H

W

E

E

L

L

T

D

A

S

A

V

R

R

S

E

R

I

L

F

L

Q

A

N

N

G

K

H

P

V

H
x
R

E

D

A
x
E

F

R

K

N

M

M

L

L

A

K

R

V

V

V

A

S

R

R

-

M

-

H

-

R

-

V

-

S

-

V

I

I

F

L

E

K

Q

L

L

L

N

V

S

Q

A

Q

W

F

D

S

V

I

L

L

R

E

T

T

M

M

T

T

P

A

S

L

D

D

Y

F

S

N

A

D

F

F

R

R

D

E

E

Y

L

L

G

S

Q

P

S

A

S

S

G

G

F

F

Q

Q

S

S

H

L

Q

Q

Y

F

R

R

Q

L

I

L

E

E

F

N

M

K

L

I

-

G

-

V

-

L

-

Q

-

F

-

K

G

G

N

E

R

E

N

N

K

E

A

L

M

L

L

L

R

K

P

S

H

E

A

Q

H

E

R

K

P

T

D

-

V

L

L

L

A

E

L

L

L

V

E

E

D

A

E
x
W

L

L

S

E

Q
x
R

-
x
T

P
|
P

S

G

L

L

Y

E

D

P

V

H

A

G

L

F

K

N

T

F

L

W

G

G

Q

K

-

L

-

E

-

K

-

N

-

I

-

T

-

R

-

G

-

L

-

E

-

F

-

I

-

R

-

Q

-

V

-

A

R

E

F

F

D

Q

L

K

P

Q

K

K

E

E

V

V

L

L

N

L

R

S

N

L

L

F

S

D

E

E

A

K

Y

R

T

H

P

E

H

H

P

L

A

L

V

S

E

K

A

G

A

E

W

R

S

R

E

L

V

S

Y

Y

R

R

N

A

T

L

E

Q

A

G

H

A

W

L

D

M

L

I

Y

Y

-

F

-

Y

-

R

-

E

-

P

-

R

-
x
F

-

Q

-

V

-

P

-

F

E

Q

L

L

A

L

E

T

K

S

L

L

V

M

D

D

F

I

E

D

D

S

Y

L

F

M

R

T

R

K

W

W

R

R

F

Y

N

N

H

H

V

V

T

C

T

M

V

V

E

H

R

R

V

M

I

L

G

G

binding alpha-methyl-L-tryptophan: R64 (≠ H78), E66 (≠ A80), W155 (≠ E158), R158 (≠ Q161), T159 (vs. gap), P160 (= P162), F239 (vs. gap)

Sites not aligning to the query:

binding alpha-methyl-L-tryptophan: 309

7lu7CCC Tryptophan 2,3-dioxygenase
28% identity, 81% coverage: 20:244/277 of query aligns to 2:279/323 of 7lu7CCC

query
sites
7lu7CCC

M

L

S

I

Y
|
Y

G

G

D

N

Y
|
Y

L

L

S

H

L

L

D

E

L

K

L

V

L

L

N

N

A

A

Q

Q

K

E

T

L

W

Q

T

S

N

E

T

T

-

K

-

G

-

N

-

K

-

I

H

H

D

D

E

E

M

H

L

L

F
|
F

I

I

Q

T

H
|
H

Q

Q

T

A

S
x
Y

E

E

L

L

W

W

M

F

R

K

L

Q

A

I

I

L

H

W

E

E

L

L

T

D

A

S

A

V

R

R

S

E

R

I

L

F

L

Q

A

N

N

G

K

H

P

V

H
x
R

E

D

A
x
E

F

R

K

N

M

M

L

L

A

K

R

V

V

V

A

S

R

R

-

M

-

H

-

R

-

V

-

S

-

V

I

I

F

L

E

K

Q

L

L

L

N

V

S

Q

A

Q

W

F

D

S

V

I

L

L

R

E

T

T

M

M

T

T

P

A

S

L

D

D

Y

F

S

N

A

D

F

F

R

R

D

E

E

Y

L

L

G

S

Q

P

S
x
A

S
|
S

G
|
G

F
|
F

Q

Q

S

S

H

L

Q

Q

Y
x
F

R
|
R

Q

L

I

L

E

E

F

N

M

K

L

I

-

G

-

V

-

L

-

Q

-

N

-

M

-

R

-

Y

-

R

-

D

-

N

-

F

-

K

G

G

N

E

R

E

N

N

K

E

A

L

M

L

L

L

R

K

P

S

H

E

A

Q

H

E

R

K

P

T

D

-

V

L

L

L

A

E

L

L

L

V

E

E

D

A

E
x
W

L

L

S

E

Q
x
R

-
x
T

P
|
P

S

G

L

L

Y

E

D

P

V

H

A

G

L

F

K

N

T

F

L

W

G

G

Q

K

-

L

-

E

-

K

-

N

-

I

-

T

-

R

-

G

-

L

-

E

-

Q

-

V

-

A

R

E

F

F

D

Q

L

K

P

Q

K

K

E

E

V

V

L

L

N

L

R

S

N

L

L

F

S

D

E

E

A

K

Y

R

T

H

P

E

H

H

P

L

A

L

V

S

E

K

A

G

A

E

W

R

S

R

E

L

V

S

Y

Y

R

R

N

A

T

L

E

Q

A

G

H

A

W

L

D

M

L

I

Y

Y

-

F

-

Y

-

R

-

E

-

P

-

R

-
x
F

-

Q

-

V

-
x
P

-

F

E

Q

L

L

A

L

E

T

K

S

L

L

V

M

D

D

F

I

E

D

D

S

Y

L

F

M

R

T

R

K

W
|
W

R

R

F

Y

N

N

H
|
H

V

V

T

C

T

M

V
|
V

E

H

R

R

V

M

I

L

G

G

binding (1~{R})-1-cyclohexyl-2-[(5~{S})-5~{H}-imidazo[1,5-b]isoindol-5-yl]ethanol: Y4 (= Y22), Y7 (= Y25), F34 (= F47), H38 (= H51), A112 (≠ S119), G114 (= G121)
binding protoporphyrin ix containing fe: H38 (= H51), Y41 (≠ S54), S113 (= S120), G114 (= G121), F115 (= F122), F120 (≠ Y127), R121 (= R128), W266 (= W231), H270 (= H235), V274 (= V239)
binding alpha-methyl-L-tryptophan: R65 (≠ H78), E67 (≠ A80), W163 (≠ E158), R166 (≠ Q161), T167 (vs. gap), P168 (= P162), F246 (vs. gap), P249 (vs. gap)

8r5qC Structure of apo tdo with a bound inhibitor
27% identity, 81% coverage: 20:244/277 of query aligns to 1:282/317 of 8r5qC

query
sites
8r5qC

M

L

S

I

Y
|
Y

G

G

D

N

Y
|
Y

L
|
L

S

H

L

L

D

E

L

K

L

V

L

L

N

N

A

A

Q

Q

K

E

T

L

W

Q

T

S

N

E

T

T

-

K

-

G

-

N

-

K

-

I

H

H

D

D

E

E

M

H

L

L

F
|
F

I

I

Q

T

H
|
H

Q

Q

T

A

S

Y

E

E

L

L

W

W

M

F

R

K

L

Q

A

I

I

L

H

W

E

E

L

L

T

D

A

S

A

V

R

R

S

E

R

I

L

F

L

Q

A

N

N

G

K

H

P

V

H
x
R

E

D

A
x
E

F

R

K

N

M

M

L

L

A

K

R

V

V

V

A

S

R

R

-

M

-

H

-

R

-

V

-

S

-

V

I

I

F

L

E

K

Q

L

L

L

N

V

S

Q

A

Q

W

F

D

S

V

I

L

L

R

E

T

T

M

M

T

T

P

A

S

L

D

D

Y
x
F

S

N

A

D

F

F

R

R

D

E

E

Y

L

L

G

S

Q
x
P

S

A

S

S

G
|
G

F

F

Q
|
Q

S
|
S

H

L

Q

Q

Y

F

R

R

Q

L

I

L

E

E

-

N

-

K

-

I

-

G

F

V

M

L

L

K

G

G

N

E

R

E

N

N

K

E

A

L

M

L

L

L

R

K

-

S

-

E

-

Q

-

E

-

K

-

T

-

L

-

E

-

L

-

V

-

E

-

A

-
x
W

-

L

-

E

-
x
R

-

T

-
x
P

-

G

-

L

-

E

P

P

H

H

A

G

H

F

-

N

-

F

-

W

-

G

-

K

-

L

R

E

P

K

D

N

V

I

L

T

A

R

L

G

L

L

E

E

D

E

E

E

L

F

S

I

Q

R

P

I

S

Q

L

A

Y

K

D

E

V

E

A

S

L

E

K

E

T

K

L

E

G

E

Q

Q

-

V

-

A

R

E

F

F

D

Q

L

K

P

Q

K

K

E

E

V

V

L

L

N

L

R

S

N

L

L

F

S

D

E

E

A

K

Y

R

T

H

P

E

H

H

P

L

A

L

V

S

E

K

A

G

A

E

W

R

S

R

E

L

V

S

Y

Y

R

R

N

A

T

L

E

Q

A

G

H

A

W

L

D

M

L

I

Y

Y

-

F

-

Y

-

R

-

E

-

P

-

R

-
x
F

-

Q

-

V

-

P

-

F

E

Q

L

L

A

L

E

T

K

S

L

L

V

M

D

D

F

I

E

D

D

S

Y

L

F

M

R

T

R

K

W

W

R

R

F

Y

N

N

H
|
H

V

V

T

C

T

M

V
|
V

E

H

R

R

V
x
M

I

L

G

G

binding 3-chloranyl-~{N}-[(1~{S})-1-(6-chloranylpyridin-3-yl)-2-phenyl-ethyl]aniline: Y3 (= Y22), Y6 (= Y25), L7 (= L26), F33 (= F47), H37 (= H51), F101 (≠ Y109), P110 (≠ Q118), G113 (= G121), Q115 (= Q123), S116 (= S124), H273 (= H235), V277 (= V239), M280 (≠ V242)
binding alpha-methyl-L-tryptophan: R64 (≠ H78), E66 (≠ A80), W153 (vs. gap), R156 (vs. gap), P158 (vs. gap), F249 (vs. gap)

P48775 Tryptophan 2,3-dioxygenase; TDO; Tryptamin 2,3-dioxygenase; Tryptophan oxygenase; TO; TRPO; Tryptophan pyrrolase; Tryptophanase; EC 1.13.11.11 from Homo sapiens (Human) (see 3 papers)
36% identity, 47% coverage: 6:135/277 of query aligns to 26:166/406 of P48775

query
sites
P48775

D

D

P

K

A

S

K

Q

E

T

G

G

A

V

Q

N

M

R

S

A

F

S

D

K

G

G

R

G

M

L

S

I

Y
|
Y

G

G

D

N

Y
|
Y

L

L

S

H

L

L

D

E

L

K

L

V

L

L

N

N

A

A

Q

Q

K

E

T

L

W

Q

T

S

N

E

T

T

-

K

-

G

-

N

-

K

-

I

H

H

D

D

E

E

M

H

L

L

F
|
F

I
|
I

Q
x
T

H
|
H

Q

Q

T

A

S

Y

E

E

L

L

W

W

M

F

R

K

L

Q

A

I

I

L

H

W

E

E

L

L

T

D

A

S

A

V

R

R

S

E

R

I

L

F

L

Q

A

N

N

G

K

H

P

V

H

R

E

D

A

E

F

R

K

N

M
|
M

L

L

A

K

R

V

V

V

A

S

R

R

-

M

-

H

-

R

-

V

-

S

-

V

I

I

F

L

E

K

Q

L

L

L

N

V

S

Q

A

Q

W

F

D

S

V

I

L

L

R

E

T

T

M

M

T

T

P

A

S

L

D

D

Y
x
F

S

N

A

D

F

F

R
|
R

D

E

E

Y

L

L

G

S

Q

P

S

A

S
|
S

G

G

F

F

Q

Q

S

S

H

L

Q

Q

Y

F

R

R

Q

L

I

L

E

E

F

N

M

K

L

I

G

G

Y42 (= Y22) mutation to A: Reduces enzyme activity by 99%.
Y45 (= Y25) mutation to A: Reduces enzyme activity by 99%.
F72 (= F47) mutation to A: Abolishes enzyme activity.
FIITH 72:76 (≠ FIIQH 47:51) binding
H76 (= H51) mutation to A: Abolishes enzyme activity.
M108 (= M83) to I: in HYPTRP; reduced tryptophan 2,3-dioxygenase activity; does not affect homotetramerization; dbSNP:rs1553957997
F140 (≠ Y109) mutation to A: Reduces enzyme activity by 99%.
R144 (= R113) binding ; mutation to A: Reduces enzyme activity by 99%.
S151 (= S120) mutation to A: Reduces enzyme activity by 90%.

Sites not aligning to the query:

175 Y→G: Reduces enzyme activity.
328 binding axial binding residue; H→A: Abolishes enzyme activity.
342 binding

8r5qA Structure of apo tdo with a bound inhibitor
27% identity, 81% coverage: 20:244/277 of query aligns to 1:283/314 of 8r5qA

query
sites
8r5qA

M

L

S

I

Y
|
Y

G

G

D

N

Y
|
Y

L
|
L

S

H

L

L

D

E

L

K

L

V

L

L

N

N

A

A

Q

Q

K

E

T

L

W

Q

T

S

N

E

T

T

-

K

-

G

-

N

-

K

-

I

H

H

D

D

E

E

M

H

L

L

F
|
F

I

I

Q

T

H
|
H

Q

Q

T

A

S

Y

E

E

L

L

W

W

M

F

R

K

L

Q

A

I

I

L

H

W

E

E

L

L

T

D

A

S

A

V

R

R

S

E

R

I

L

F

L

Q

A

N

N

G

K

H

P

V

H
x
R

E

D

A
x
E

F

R

K

N

M

M

L

L

A

K

R

V

V

V

A

S

R

R

-

M

-

H

-

R

-

V

-

S

-

V

I

I

F

L

E

K

Q

L

L

L

N

V

S

Q

A

Q

W

F

D

S

V

I

L

L

R

E

T

T

M

M

T

T

P

A

S

L

D

D

Y
x
F

S

N

A

D

F

F

R

R

D

E

E

Y

L

L

G

S

Q
x
P

S

A

S

S

G
|
G

F
|
F

Q
|
Q

S
|
S

H

L

Q

Q

Y

F

R

R

Q

L

I

L

E

E

F

N

M

K

L

I

-

G

-

V

-

L

-

Q

-

K

G

G

N

E

R

E

N

N

K

E

A

L

M

L

L

L

R

K

-

S

-

E

-

Q

-

E

-

K

-

T

-

L

-

E

-

L

-

V

-

E

-

A

-
x
W

-

L

-

E

-
x
R

-
x
T

-
x
P

-

G

-

L

-

E

P

P

H

H

A

G

H

F

-

N

-

F

-

W

-

G

-

K

-

L

R

E

P

K

D

N

V

I

L

T

A

R

L

G

L

L

E

E

D

E

E

E

L

F

S

I

Q

R

P

I

S

Q

L

A

Y

K

D

E

V

E

A

S

L

E

K

E

T

K

L

E

G

E

Q

Q

-

V

-

A

R

E

F

F

D

Q

L

K

P

Q

K

K

E

E

V

V

L

L

N

L

R

S

N

L

L

F

S

D

E

E

A

K

Y

R

T

H

P

E

H

H

P

L

A

L

V

S

E

K

A

G

A

E

W

R

S

R

E

L

V

S

Y

Y

R

R

N

A

T

L

E

Q

A

G

H

A

W

L

D

M

L

I

Y

Y

-

F

-

Y

-

R

-

E

-

P

-

R

-
x
F

-

Q

-

V

-

P

-

F

E

Q

L

L

A

L

E

T

K

S

L

L

V

M

D

D

F

I

E

D

D

S

Y

L

F

M

R

T

R

K

W

W

R

R

F

Y

N

N

H
|
H

V

V

T

C

T

M

V
|
V

E

H

R

R

V
x
M

I

L

G

G

binding 3-chloranyl-~{N}-[(1~{S})-1-(6-chloranylpyridin-3-yl)-2-phenyl-ethyl]aniline: Y3 (= Y22), Y6 (= Y25), L7 (= L26), F33 (= F47), H37 (= H51), F101 (≠ Y109), P110 (≠ Q118), G113 (= G121), F114 (= F122), Q115 (= Q123), S116 (= S124), H274 (= H235), V278 (= V239), M281 (≠ V242)
binding alpha-methyl-L-tryptophan: R64 (≠ H78), E66 (≠ A80), W154 (vs. gap), R157 (vs. gap), T158 (vs. gap), P159 (vs. gap), F250 (vs. gap)

8r5qB Structure of apo tdo with a bound inhibitor
27% identity, 81% coverage: 20:244/277 of query aligns to 1:284/318 of 8r5qB

query
sites
8r5qB

M

L

S

I

Y
|
Y

G

G

D

N

Y
|
Y

L
|
L

S

H

L

L

D

E

L

K

L

V

L

L

N

N

A

A

Q

Q

K

E

T

L

W

Q

T

S

N

E

T

T

-

K

-

G

-

N

-

K

-

I

H

H

D

D

E

E

M

H

L

L

F
|
F

I

I

Q

T

H
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H

Q

Q

T

A

S

Y

E

E

L

L

W

W

M

F

R

K

L

Q

A

I

I

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H

W

E

E

L

L

T

D

A

S

A

V

R

R

S

E

R

I

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F

L

Q

A

N

N

G

K

H

P

V

H
x
R

E

D

A
x
E

F

R

K

N

M

M

L

L

A

K

R

V

V

V

A

S

R

R

-

M

-

H

-

R

-

V

-

S

-

V

I

I

F

L

E

K

Q

L

L

L

N

V

S

Q

A

Q

W

F

D

S

V

I

L

L

R

E

T

T

M

M

T

T

P

A

S

L

D

D

Y
x
F

S

N

A

D

F

F

R

R

D

E

E

Y

L

L

G

S

Q
x
P

S

A

S

S

G
|
G

F

F

Q
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Q

S
|
S

H

L

Q

Q

Y

F

R

R

Q

L

I

L

E

E

F

N

M

K

L

I

-

G

-

V

-

L

-

Q

-

F

-

K

G

G

N

E

R

E

N

N

K

E

A

L

M

L

L

L

R

K

-

S

-

E

-

Q

-

E

-

K

-

T

-

L

-

E

-

L

-

V

-

E

-

A

-
x
W

-

L

-

E

-
x
R

-

T

-
x
P

-

G

-

L

-

E

P

P

H

H

A

G

H

F

-

N

-

F

-

W

-

G

-

K

-

L

R

E

P

K

D

N

V

I

L

T

A

R

L

G

L

L

E

E

D

E

E

E

L

F

S

I

Q

R

P

I

S

Q

L

A

Y

K

D

E

V

E

A

S

L

E

K

E

T

K

L

E

G

E

Q

Q

-

V

-

A

R

E

F

F

D

Q

L

K

P

Q

K

K

E

E

V

V

L

L

N

L

R

S

N

L

L

F

S

D

E

E

A

K

Y

R

T

H

P

E

H

H

P

L

A

L

V

S

E

K

A

G

A

E

W

R

S

R

E

L

V

S

Y

Y

R

R

N

A

T

L

E

Q

A

G

H

A

W

L

D

M

L

I

Y

Y

-

F

-

Y

-

R

-

E

-

P

-

R

-
x
F

-

Q

-

V

-

P

-

F

E

Q

L

L

A

L

E

T

K

S

L

L

V

M

D

D

F

I

E

D

D

S

Y

L

F

M

R

T

R

K

W

W

R

R

F

Y

N

N

H
|
H

V

V

T

C

T

M

V
|
V

E

H

R

R

V
x
M

I

L

G

G

binding 3-chloranyl-~{N}-[(1~{S})-1-(6-chloranylpyridin-3-yl)-2-phenyl-ethyl]aniline: Y3 (= Y22), Y6 (= Y25), L7 (= L26), F33 (= F47), H37 (= H51), F101 (≠ Y109), P110 (≠ Q118), G113 (= G121), Q115 (= Q123), S116 (= S124), H275 (= H235), V279 (= V239), M282 (≠ V242)
binding alpha-methyl-L-tryptophan: R64 (≠ H78), E66 (≠ A80), W155 (vs. gap), R158 (vs. gap), P160 (vs. gap), F251 (vs. gap)

5ti9D Crystal structure of human tdo in complex with trp and dioxygen, northeast structural genomics consortium target hr6161 (see paper)
27% identity, 93% coverage: 20:277/277 of query aligns to 2:322/332 of 5ti9D

query
sites
5ti9D

M

L

S

I

Y

Y

G

G

D

N

Y

Y

L

L

S

H

L

L

D

E

L

K

L

V

L

L

N

N

A

A

Q

Q

K

E

T

L

W

Q

T

S

N

E

T

T

-

K

-

G

-

N

-

K

-

I

H

H

D

D

E

E

M

H

L

L

F
|
F

I

I

Q

T

H
|
H

Q

Q

T

A

S
x
Y

E

E

L

L

W

W

M

F

R

K

L

Q

A

I

I

L

H

W

E

E

L

L

T

D

A

S

A

V

R

R

S

E

R

I

L

F

L

Q

A

N

N

G

K

H

P

V

H
x
R

E

D

A
x
E

F

R

K

N

M

M

L

L

A

K

R

V

V

V

A

S

R

R

-

M

-

H

-

R

-

V

-

S

-

V

I

I

F

L

E

K

Q

L

L

L

N

V

S

Q

A

Q

W

F

D

S

V

I

L
|
L

R

E

T

T

M

M

T

T

P

A

S

L

D

D

Y

F

S

N

A

D

F

F

R
|
R

D

E

E

Y

L
|
L

G

S

Q

P

S
x
A

S
|
S

G
|
G

F
|
F

Q

Q

S

S

H

L

Q

Q

Y
x
F

R
|
R

Q

L

I

L

E

E

F

N

M

K

L

I

G

G

-

V

-

L

-

Q

-

N

-

M

-

R

-

V

-

P

-
x
Y

N

N

R

R

-

R

-

H

-

Y

-

R

-

D

-

N

-

F

-

K

-

G

-

E

N

N

K

E

A

L

M

L

L

L

R

K

P

S

H

E

A

Q

H

E

R

K

P

T

D

-

V

L

L

L

A

E

L

L

L

V

E

E

D

A

E
x
W

L

L

S

E

Q
x
R

-
x
T

P
|
P

S

G

L

L

Y

E

D

P

V

H

A

G

L

F

K

N

T

F

L

W

G

G

Q

K

-

L

-

E

-

K

-

N

-

I

-

T

-

R

-

G

-

L

-

E

-

F

-

I

-

R

-

I

-

Q

-

A

-

E

-

K

-

E

-

Q

-

V

-

A

R

E

F

F

D

Q

L

K

P

Q

K

K

E

E

V

V

L

L

N

L

R

S

N

L

L

F

S

D

E

E

A

K

Y

R

T

H

P

E

H

H

P

L

A

L

V

S

E

K

A

G

A

E

W

R

S

R

E

L

V

S

Y

Y

R

R

N

A

T

L

E

Q

A

G

H

A

W

L

D

M

L
x
I

Y

Y

-

F

-

Y

-

R

-

E

-

P

-

R

-
x
F

-

Q

-

V

-
x
P

-

F

E

Q

L

L

A

L

E

T

K

S

L

L

V

M

D

D

F

I

E

D

D

S

Y

L

F

M

R

T

R

K

W

W

R

R

F

Y

N

N

H
|
H

V

V

T

C

T
x
M

V
|
V

E

H

R

R

V

M

I

L

G

G

F

-

K

-

R

-

G

-

T

-

G

-

T

-

G

S

G

G

V

Y

S

H

Y
|
Y

L
|
L

K

R

R

S

M

T

L

V

E

S

-

D

-

R

V

Y

E

K

L

V

F

F

P

V

E

D

L

L

W

F

H

N

L

L

R

S

T

T

A

Y

L

L

binding protoporphyrin ix containing fe: F34 (= F47), H38 (= H51), Y41 (≠ S54), L94 (= L101), S113 (= S120), G114 (= G121), F115 (= F122), F120 (≠ Y127), R121 (= R128), Y137 (vs. gap), H286 (= H235), M289 (≠ T238), V290 (= V239), Y300 (= Y257), L301 (= L258)
binding N'-Formylkynurenine: F34 (= F47), H38 (= H51), R106 (= R113), L109 (= L116), A112 (≠ S119), S113 (= S120), G114 (= G121)
binding tryptophan: R65 (≠ H78), E67 (≠ A80), W170 (≠ E158), R173 (≠ Q161), T174 (vs. gap), P175 (= P162), I253 (≠ L214), F262 (vs. gap), P265 (vs. gap)

Query Sequence

>GFF980 FitnessBrowser__Phaeo:GFF980
MSTPYDPAKEGAQMSFDGRMSYGDYLSLDLLLNAQKTWTNTHDEMLFIIQHQTSELWMRL
AIHELTAARSRLLANKPHEAFKMLARVARIFEQLNSAWDVLRTMTPSDYSAFRDELGQSS
GFQSHQYRQIEFMLGNRNKAMLRPHAHRPDVLALLEDELSQPSLYDVALKTLGQRFDLPK
EVLNRNLSEAYTPHPAVEAAWSEVYRNTEAHWDLYELAEKLVDFEDYFRRWRFNHVTTVE
RVIGFKRGTGGTGGVSYLKRMLEVELFPELWHLRTAL

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