SitesBLAST

3tcyA Crystallographic structure of phenylalanine hydroxylase from chromobacterium violaceum (cpah) bound to phenylalanine in a site distal to the active site (see paper)
49% identity, 88% coverage: 14:245/263 of query aligns to 25:258/277 of 3tcyA

query
sites
3tcyA

Q

Q

G

P

F

L

I

D

H

R

Y

Y

T

S

A

A

E

E

E

D

H

H

A

A

V

T

W

W

N

A

T

T

L

L

I

Y

T

Q

R

R

Q

Q

L

C

K

K

V

L

L

L

E

P

G

G

R

R

A

A

C

C

Q

D

E

E

Y

F

M

L

D

E

G

G

I

L

E

E

K

R

L

L

G

E

L

V

P

D

H

A

D

D

R

R

I

V

P

P

Q

D

L

F

D

N

E

K

I

L

N

N

K

E

V

K

L

L

G

M

E

A

T

A

T

T

G

G

W

W

Q

K

V

I

A

V

R

A

V

V

P

P

A

G

L

L

I

I

P

P

F

D

Q

D

T

V

F

F

E

E

L

H

L

L

A

A

S

N

K

R

Q

R

F

F

P

P

V

V

A

T

T

W

F

W

I

L

R

R

T

E

R

P

E

H

E

Q

L

L

D

D

Y

Y

L

L

Q

Q

E

E

P

P

D

D

I

V

F

F

H
|
H

E

D

I

L

F

F

G

G

H
|
H

C

V

P

P

L

L

T

I

N

N

P

P

W

V

F

F

A

A

E

D

F

Y

T

L

H

E

T
x
A

Y
|
Y

G

G

K

K

L

G

G

G

L

V

Q
x
K

A

A

S

K

K

A

E

L

E

G

R

A

V

L

-

P

Y

M

L
|
L

A

A

R

R

L

L

Y

Y

W

W

M

Y

T

T

I

V

E
|
E

F

F

G

G

L

L

V

I

D

N

T

T

P

P

Q

A

G

G

K

M

R

R

I

I

Y

Y

G

G

G

A

G

G

I

I

L

L

S
|
S

S

S

P

K

K

S

E

E

T

S

V

I

Y

Y

S

C

L

L

-

D

S

S

G

A

E

S

P

P

E

N

H

R

Q

V

A

G

F

F

D

D

P

L

L

M

E

R

A

I

M

M

R

N

T

T

P

R

Y

Y

R

R

I

I

D

D

I

T

L

F

Q

Q

P

K

L

T

Y

Y

F

F

V

V

L

I

P

D

N

S

L

F

K

K

R

Q

L

L

F

F

D

D

L

A

A
x
T

H

A

E
x
P

D
|
D

I
x
F

M

A

G

P

M

L

V

Y

H

L

Q

Q

active site: H132 (= H121), H137 (= H126), E178 (= E166), S197 (= S185)
binding cobalt (ii) ion: H132 (= H121), H137 (= H126), E178 (= E166)
binding phenylalanine: A152 (≠ T141), Y153 (= Y142), K159 (≠ Q148), L169 (= L157), T248 (≠ A235), P250 (≠ E237), D251 (= D238), F252 (≠ I239)

1ltzA Crystal structure of chromobacterium violaceum phenylalanine hydroxylase, structure has bound iron (iii) and oxidized cofactor 7, 8-dihydrobiopterin (see paper)
51% identity, 82% coverage: 18:233/263 of query aligns to 29:246/274 of 1ltzA

query
sites
1ltzA

H

R

Y

Y

T

S

A

A

E

E

E

D

H

H

A

A

V

T

W

W

N

A

T

T

L

L

I

Y

T

Q

R

R

Q

Q

L

C

K

K

V

L

L

L

E

P

G

G

R

R

A

A

C

C

Q

D

E

E

Y

F

M

L

D

E

G

G

I

L

E

E

K

R

L

L

G

E

L

V

P

D

H

A

D

D

R

R

I

V

P

P

Q

D

L

F

D

N

E

K

I

L

N

N

K

E

V

K

L

L

G

M

E

A

T

A

T

T

G

G

W

W

Q

K

V

I

A

V

R

A

V

V

P

P

A

G

L

L

I
|
I

P

P

F
x
D

Q

D

T

V

F
|
F

F

F

E

E

L

H

L

L

A

A

S

N

K

R

Q

R

F

F

P

P

V

V

A

T

T

W

F

W

I

L

R

R

T

E

R

P

E

H

E

Q

L

L

D

D

Y

Y

L

L

Q

Q

E

E

P

P

D

D

I

V

F

F

H
|
H

E

D

I

L

F

F

G

G

H
|
H

C

V

P

P

L

L

T

I

N

N

P

P

W

V

F

F

A

A

E

D

F

Y

T

L

H

E

T

A

Y

Y

G

G

K

K

L

G

G

G

L

V

Q

K

A

A

S

K

K

A

E

L

E

G

R

A

V

L

-

P

Y

M

L

L

A

A

R

R

L

L

Y
|
Y

W

W

M

Y

T

T

I

V

E
|
E

F

F

G

G

L

L

V

I

D

N

T

T

P

P

Q

A

G

G

K

M

R

R

I

I

Y

Y

G

G

G

A

G

G

I

I

L

L

S
|
S

S

S

P

K

K

S

E

E

T

S

V

I

Y

Y

S

C

L

L

-

D

S

S

G

A

E

S

P

P

E

N

H

R

Q

V

A

G

F

F

D

D

P

L

L

M

E

R

A

I

M

M

R

N

T

T

P

R

Y

Y

R

R

I

I

D

D

I

T

L

F

Q

Q

P

K

L

T

Y

Y

F

F

V

V

L

I

P

D

N

S

L

F

K

K

R

Q

L

L

F

F

D

D

active site: H132 (= H121), H137 (= H126), E178 (= E166), S197 (= S185)
binding fe (iii) ion: H132 (= H121), H137 (= H126), E178 (= E166)
binding 7,8-dihydrobiopterin: I96 (= I85), D98 (≠ F87), F101 (= F90), Y173 (= Y161)

P04177 Tyrosine 3-monooxygenase; Tyrosine 3-hydroxylase; TH; EC 1.14.16.2 from Rattus norvegicus (Rat) (see 7 papers)
39% identity, 79% coverage: 17:224/263 of query aligns to 223:434/498 of P04177

query
sites
P04177

I

V

H

E

Y

Y

T

T

A

A

E

E

H

I

A

A

V

T

W

W

N

K

T

E

L

V

I

Y

T

V

R

T

Q

L

L

K

K

G

V

L

L

Y

E

A

G

T

R

H

A

A

C

C

Q

R

E

E

Y

H

M

L

D

E

G

G

I

F

E

Q

K

L

L

L

-

E

-

R

-

Y

-

C

G

G

L

Y

P

R

H

E

D

D

R

S

I

I

P

P

Q

Q

L

L

D

E

E

D

I

V

N

S

K

R

V

F

L

L

G

K

E

E

T

R

T

T

G

G

W

F

Q

Q

V

L

A

R

R

P

V

V

P

A

A

G

L

L

I

L

P

S

F

A

Q

R

T

D

F

F

F

L

E

A

L

S

L

L

A

A

S

F

K

R

Q

V

F

F

P
x
Q

V

C

A

T

T

Q

F

Y

I

I

R

R

T

H

R

A

E

S

L

P

D

M

Y
x
H

L

S

Q

P

E

E

P

P

D

D

I

C

F

C

H
|
H

E

E

I

L

F

L

G

G

H
|
H

C

V

P

P

L

M

L

L

T

A

N

D

P

R

W

T

F

F

A

A

E

Q

F

F

T

S

H

Q

T

D

Y

I

G

G

K

L

L

A

G

S

L

L

Q

G

A

A

S

S

K

D

E

E

R

I

V

E

Y

K

L

L

A

S

R

T

L

V

Y

Y

W
|
W

M

F

T

T

I

V

E
|
E

F

F

G

G

L

L

V

C

D

K

T

Q

P

N

Q

G

G

E

K

L

R

K

I

A

Y

Y

G

G

G

A

G

G

I

L

L

L

S

S

P

Y

K

G

E

E

T

L

V

L

Y

H

S

S

L

L

S

S

G

E

E

E

P

P

E

E

H

V

Q

R

A

A

F

F

D

D

P

P

L

D

E

T

A

A

M

A

R

V

T

Q

P

P

Y

Y

R

Q

I
x
D

D

Q

I

T

L

Y

Q

Q

P

P

L

V

Y

Y

F

F

V

V

Q310 (≠ P100) mutation to H: Does not affect Vmax for phenylalanine. Increases KM for phenylalanine.
H323 (≠ Y113) mutation to Y: Does not affect Vmax for phenylalaninet. Increases KM for phenylalanine.
H331 (= H121) binding
H336 (= H126) binding
W372 (= W162) mutation to F: Does not affect substrate specificity.
E376 (= E166) binding
D425 (≠ I215) Important for substrate specificity; mutation to V: Shifts substrate specificity from tyrosine to phenylalanine.

Sites not aligning to the query:

1 modified: Initiator methionine, Removed
19 modified: Phosphoserine; by CaMK2
31 modified: Phosphoserine
40 modified: Phosphoserine; by CaMK2 and PKA

P17289 Tyrosine 3-monooxygenase; Tyrosine 3-hydroxylase; TH; EC 1.14.16.2 from Bos taurus (Bovine) (see 2 papers)
38% identity, 79% coverage: 17:224/263 of query aligns to 216:427/491 of P17289

query
sites
P17289

I

V

H

E

Y

Y

T

T

A

A

E

E

H

T

A

A

V

T

W

W

N

K

T

E

L

V

I

Y

T

S

R

T

Q

L

L

R

K

G

V

L

L

Y

E

P

G

T

R

H

A

A

C

C

Q

R

E

E

Y

H

M

L

D

E

G

A

I

F

E

E

K

L

L

L

-

E

-

R

-

F

-

C

G

G

L

Y

P

R

H

E

D

D

R

R

I

I

P

P

Q

Q

L

L

D

E

E

D

I

V

N

S

K

R

V

F

L

L

G

K

E

E

T

R

T

T

G

G

W

F

Q

Q

V

L

A

R

R

P

V

A

P

A

A

G

L

L

I

L

P

S

F

A

Q

R

T

D

F

F

F

L

E

A

L

S

L

L

A

A

S

F

K

R

Q

V

F

F

P

Q

V

C

A

T

T

Q

F

Y

I

I

R

R

T

H

R

A

E

S

L

P

D

M

Y

H

L

S

Q

P

E

E

P

P

D

E

I

C

F

C

H

H

E

E

I

L

F

L

G

G

H

H

C

V

P

P

L

M

L

L

T

A

N

D

P

R

W

T

F

F

A

A

E

Q

F

F

T

S

H

Q

T

D

Y

I

G

G

K

L

L

A

G

S

L

L

Q

G

A

V

S

S

K

D

E

E

R

I

V

E

Y

K

L

L

A

S

R

T

L

L

Y

Y

W

W

M

F

T

T

I

V

E

E

F

F

G

G

L

L

V

C

D

K

T

Q

P

N

Q

G

G

E

K

V

R

K

I

A

Y

Y

G

G

G

A

G

G

I

L

L

L

S

S

P

Y

K

G

E

E

T

L

V

L

Y

H

S

S

L

L

S

S

G

E

E

E

P

P

E

E

H

I

Q

R

A

A

F

F

D

D

P

P

L

D

E

A

A

A

M

A

R

V

T

Q

P

P

Y

Y

R

Q

I

D

D

Q

I

T

L

Y

Q

Q

P

P

L

V

Y

Y

F

F

V

V

Sites not aligning to the query:

1 modified: Initiator methionine, Removed
19 modified: Phosphoserine; by CaMK2
31 modified: Phosphoserine
40 modified: Phosphoserine; by CaMK2 and PKA

2tohA Tyrosine hydroxylase catalytic and tetramerization domains from rat (see paper)
38% identity, 79% coverage: 17:224/263 of query aligns to 61:272/336 of 2tohA

query
sites
2tohA

I

V

H

E

Y

Y

T

T

A

A

E

E

H

I

A

A

V

T

W

W

N

K

T

E

L

V

I

Y

T

V

R

T

Q

L

L

K

K

G

V

L

L

Y

E

A

G

T

R

H

A

A

C

C

Q

R

E

E

Y

H

M

L

D

E

G

G

I

F

E

Q

K

L

L

L

-

E

-

R

-

Y

-

C

G

G

L

Y

P

R

H

E

D

D

R

S

I

I

P

P

Q

Q

L

L

D

E

E

D

I

V

N

S

K

R

V

F

L

L

G

K

E

E

T

R

T

T

G

G

W

F

Q

Q

V

L

A

R

R

P

V
|
V

P

A

A

G

L
|
L

I
x
L

P

S

F

A

Q

R

T

D

F
x
Y

F

L

E

A

L

S

L

L

A

A

S

F

K

R

Q

V

F

F

P

Q

V

C

A

T

T

Q

F

Y

I

I

R

R

T

H

R

A

E

S

L

P

D

M

Y

H

L

S

Q

P

E

E

P
|
P

D

D

I

C

F

C

H
|
H

E
|
E

I

L

F

L

G

G

H
|
H

C

V

P

P

L

M

L

L

T

A

N

D

P

R

W

T

F

F

A

A

E

Q

F

F

T

S

H

Q

T

D

Y

I

G

G

K

L

L

A

G

S

L

L

Q

G

A

A

S

S

K

D

E

E

R

I

V

E

Y

K

L

L

A

S

R

T

L

V

Y
|
Y

W

W

M

F

T

T

I

V

E
|
E

F

F

G

G

L

L

V

C

D

K

T

Q

P

N

Q

G

G

E

K

L

R

K

I

A

Y

Y

G

G

G

A

G

G

I

L

L

L

S
|
S

S

S

P

Y

K

G

E

E

T

L

V

L

Y

H

S

S

L

L

S

S

G

E

E

E

P

P

E

E

H

V

Q

R

A

A

F

F

D

D

P

P

L

D

E

T

A

A

M

A

R

V

T

Q

P

P

Y

Y

R

Q

I

D

D

Q

I

T

L

Y

Q

Q

P

P

L

V

Y

Y

F

F

V

V

active site: H169 (= H121), H174 (= H126), E214 (= E166), S233 (= S185)
binding fe (iii) ion: H169 (= H121), H174 (= H126), E214 (= E166)
binding 7,8-dihydrobiopterin: V129 (= V81), L132 (= L84), L133 (≠ I85), Y138 (≠ F90), P165 (= P117), E170 (= E122), Y209 (= Y161)

2xsnA Crystal structure of human tyrosine hydroxylase catalytic domain
38% identity, 79% coverage: 17:224/263 of query aligns to 61:272/335 of 2xsnA

query
sites
2xsnA

I

V

H

E

Y

Y

T

T

A

A

E

E

H

I

A

A

V

T

W

W

N

K

T

E

L

V

I

Y

T

T

R

T

Q

L

L

K

K

G

V

L

L

Y

E

A

G

T

R

H

A

A

C

C

Q

G

E

E

Y

H

M

L

D

E

G

A

I

F

E

A

K

L

L

L

-

E

-

R

-

F

-

S

G

G

L

Y

P

R

H

E

D

D

R

N

I

I

P

P

Q

Q

L

L

D

E

E

D

I

V

N

S

K

R

V

F

L

L

G

K

E

E

T

R

T

T

G

G

W

F

Q

Q

V

L

A

R

R

P

V

V

P

A

A

G

L

L

I

L

P

S

F

A

Q

R

T

D

F

F

F

L

E

A

L

S

L

L

A

A

S

F

K

R

Q

V

F

F

P

Q

V

C

A

T

T

Q

F

Y

I

I

R

R

T

H

R

A

E

S

L

P

D

M

Y

H

L

S

Q

P

E

E

P

P

D

D

I

C

F

C

H
|
H

E

E

I

L

F

L

G

G

H
|
H

C

V

P

P

L

M

L

L

T

A

N

D

P

R

W

T

F

F

A

A

E

Q

F

F

T

S

H

Q

T

D

Y

I

G

G

K

L

L

A

G

S

L

L

Q

G

A

A

S

S

K

D

E

E

R

I

V

E

Y

K

L

L

A

S

R

T

L

L

Y

Y

W

W

M

F

T

T

I

V

E
|
E

F

F

G

G

L

L

V

C

D

K

T

Q

P

N

Q

G

G

E

K

V

R

K

I

A

Y

Y

G

G

G

A

G

G

I

L

L

L

S
|
S

S

S

P

Y

K

G

E

E

T

L

V

L

Y

H

S

C

L

L

S

S

G

E

E

E

P

P

E

E

H

I

Q

R

A

A

F

F

D

D

P

P

L

E

E

A

A

A

M

A

R

V

T

Q

P

P

Y

Y

R

Q

I

D

D

Q

I

T

L

Y

Q

Q

P

S

L

V

Y

Y

F

F

V

V

active site: H169 (= H121), H174 (= H126), E214 (= E166), S233 (= S185)
binding zinc ion: H169 (= H121), H174 (= H126), E214 (= E166)

6zvpD Atomic model of the em-based structure of the full-length tyrosine hydroxylase in complex with dopamine (residues 40-497) in which the regulatory domain (residues 40-165) has been included only with the backbone atoms (see paper)
38% identity, 79% coverage: 17:224/263 of query aligns to 183:394/458 of 6zvpD

query
sites
6zvpD

I

V

H

E

Y

Y

T

T

A

A

E

E

H

I

A

A

V

T

W

W

N

K

T

E

L

V

I

Y

T

T

R

T

Q

L

L

K

K

G

V

L

L

Y

E

A

G

T

R

H

A

A

C

C

Q

G

E

E

Y

H

M

L

D

E

G

A

I

F

E

A

K

L

L

L

-

E

-

R

-

F

-

S

G

G

L

Y

P

R

H

E

D

D

R

N

I

I

P

P

Q

Q

L

L

D

E

E

D

I

V

N

S

K

R

V

F

L

L

G

K

E

E

T

R

T

T

G

G

W

F

Q

Q

V

L

A

R

R

P

V

V

P

A

A

G

L

L

I

L

P

S

F

A

Q

R

T

D

F

F

F

L

E

A

L

S

L

L

A

A

S

F

K

R

Q

V

F

F

P

Q

V

C

A

T

T

Q

F

Y

I

I

R

R

T

H

R

A

E

S

L

P

D

M

Y

H

L

S

Q

P

E

E

P
|
P

D

D

I

C

F

C

H
|
H

E

E

I

L

F

L

G

G

H
|
H

C

V

P

P

L

M

L

L

T

A

N

D

P

R

W

T

F

F

A

A

E

Q

F

F

T

S

H

Q

T

D

Y

I

G

G

K

L

L

A

G

S

L

L

Q

G

A

A

S

S

K

D

E

E

R

I

V

E

Y

K

L

L

A

S

R

T

L

L

Y
|
Y

W

W

M

F

T

T

I

V

E
|
E

F

F

G

G

L

L

V

C

D

K

T

Q

P

N

Q

G

G

E

K

V

R

K

I

A

Y

Y

G

G

G
x
A

G

G

I

L

L

L

S

S

P

Y

K

G

E

E

T

L

V

L

Y

H

S

C

L

L

S

S

G

E

E

E

P

P

E

E

H

I

Q

R

A

A

F

F

D

D

P

P

L

E

E

A

A

A

M

A

R

V

T

Q

P

P

Y

Y

R

Q

I

D

D

Q

I

T

L

Y

Q

Q

P

S

L

V

Y

Y

F

F

V

V

binding fe (iii) ion: H291 (= H121), H296 (= H126), E336 (= E166), A351 (≠ G181)
binding l-dopamine: P287 (= P117), H291 (= H121), H296 (= H126), Y331 (= Y161), E336 (= E166)

Sites not aligning to the query:

binding l-dopamine: 2

6zn2A Partial structure of tyrosine hydroxylase in complex with dopamine showing the catalytic domain and an alpha-helix from the regulatory domain involved in dopamine binding. (see paper)
38% identity, 79% coverage: 17:224/263 of query aligns to 60:271/335 of 6zn2A

query
sites
6zn2A

I

V

H

E

Y

Y

T

T

A

A

E

E

H

I

A

A

V

T

W

W

N

K

T

E

L

V

I

Y

T

T

R

T

Q

L

L

K

K

G

V

L

L

Y

E

A

G

T

R

H

A

A

C

C

Q

G

E

E

Y

H

M

L

D

E

G

A

I

F

E

A

K

L

L

L

-

E

-

R

-

F

-

S

G

G

L

Y

P

R

H

E

D

D

R

N

I

I

P

P

Q

Q

L

L

D

E

E

D

I

V

N

S

K

R

V

F

L

L

G

K

E

E

T

R

T

T

G

G

W

F

Q

Q

V

L

A

R

R

P

V

V

P

A

A

G

L

L

I

L

P

S

F
x
A

Q

R

T

D

F

F

F

L

E

A

L

S

L

L

A

A

S

F

K

R

Q

V

F

F

P

Q

V

C

A

T

T

Q

F

Y

I

I

R

R

T

H

R

A

E

S

L

P

D

M

Y

H

L

S

Q

P

E

E

P
|
P

D

D

I

C

F

C

H
|
H

E

E

I

L

F

L

G

G

H
|
H

C

V

P

P

L

M

L

L

T

A

N

D

P

R

W

T

F

F

A

A

E

Q

F

F

T

S

H

Q

T

D

Y

I

G

G

K

L

L

A

G

S

L

L

Q

G

A

A

S

S

K

D

E

E

R

I

V
x
E

Y

K

L

L

A
x
S

R

T

L

L

Y
|
Y

W
|
W

M

F

T

T

I

V

E
|
E

F

F

G

G

L

L

V

C

D

K

T

Q

P

N

Q

G

G

E

K

V

R

K

I

A

Y

Y

G

G

G

A

G

G

I

L

L

L

S

S

P

Y

K

G

E

E

T

L

V

L

Y

H

S

C

L

L

S

S

G

E

E

E

P

P

E

E

H

I

Q

R

A

A

F

F

D

D

P

P

L

E

E

A

A

A

M

A

R

V

T

Q

P

P

Y
|
Y

R

Q

I

D

D

Q

I

T

L

Y

Q

Q

P

S

L

V

Y

Y

F

F

V

V

binding fe (iii) ion: H168 (= H121), H173 (= H126), E213 (= E166)
binding l-dopamine: P164 (= P117), H173 (= H126), E213 (= E166)
binding : A134 (≠ F87), E202 (≠ V155), S205 (≠ A158), Y208 (= Y161), W209 (= W162), Y260 (= Y213)

P07101 Tyrosine 3-monooxygenase; Tyrosine 3-hydroxylase; TH; EC 1.14.16.2 from Homo sapiens (Human) (see 32 papers)
38% identity, 79% coverage: 17:224/263 of query aligns to 253:464/528 of P07101

query
sites
P07101

I

V

H

E

Y

Y

T

T

A

A

E

E

E
|
E

H

I

A

A

V

T

W

W

N

K

T

E

L

V

I

Y

T

T

R

T

Q

L

L

K

K

G

V

L

L

Y

E

A

G
x
T

R

H

A

A

C

C

Q

G

E

E

Y

H

M

L

D

E

G

A

I

F

E

A

K

L

L

L

-

E

-

R

-

F

-

S

G

G

L

Y

P

R

H

E

D

D

R

N

I

I

P
|
P

Q

Q

L

L

D

E

E

D

I

V

N

S

K

R

V
x
F

L

L

G

K

E

E

T

R

T
|
T

G

G

W

F

Q

Q

V

L

A
x
R

R

P

V

V

P

A

A

G

L

L

I

L

P

S

F

A

Q
x
R

T

D

F

F

F

L

E

A

L

S

L

L

A

A

S

F

K
x
R

Q

V

F

F

P

Q

V

C

A

T

T

Q

F

Y

I

I

R

R

T

H

R

A

E

S

L

P

D

M

Y

H

L

S

Q

P

E

E

P

P

D

D

I
x
C

F

C

H

H

E

E

I

L

F

L

G

G

H

H

C

V

P

P

L

M

L

L

T

A

N

D

P

R

W

T

F
|
F

A
|
A

E

Q

F

F

T

S

H

Q

T

D

Y

I

G

G

K

L

L

A

G

S

L
|
L

Q

G

A

A

S

S

K

D

E

E

R
x
I

V

E

Y

K

L

L

A

S

R
x
T

L

L

Y

Y

W

W

M

F

T

T

I

V

E

E

F

F

G

G

L

L

V

C

D

K

T
x
Q

P

N

Q
x
G

G

E

K

V

R

K

I

A

Y

Y

G

G

G

A

G

G

I

L

L

L

S

S

P

Y

K
x
G

E

E

T

L

V

L

Y

H

S

C

L

L

S

S

G

E

E

E

P

P

E

E

H

I

Q
x
R

A

A

F

F

D

D

P

P

L

E

E

A

A

A

M

A

R

V

T

Q

P

P

Y

Y

R

Q

I

D

D

Q

I

T

L

Y

Q

Q

P

S

L

V

Y

Y

F

F

V

V

E259 (= E23) to G: in ARSEGS; complete loss of tyrosine 3-monooxygenase activity
T276 (≠ G40) to P: in ARSEGS; parkinsonian symptoms in infancy; no effect on tyrosine 3-monooxygenase activity; dbSNP:rs28934581
P301 (= P61) to A: in ARSEGS; loss of over 80% of tyrosine 3-monooxygenase activity
F309 (≠ V69) to S: in ARSEGS; complete loss of tyrosine 3-monooxygenase activity
T314 (= T74) to M: in ARSEGS; parkinsonian symptoms in infancy; loss of about 80% of tyrosine 3-monooxygenase activity; dbSNP:rs121917764
R319 (≠ A79) to P: in ARSEGS; complete loss of tyrosine 3-monooxygenase activity
R328 (≠ Q88) to W: in ARSEGS; complete loss of tyrosine 3-monooxygenase activity; dbSNP:rs1428589694
R337 (≠ K97) to H: in ARSEGS; parkinsonian symptoms in infancy; no effect on tyrosine 3-monooxygenase activity; dbSNP:rs28934580
C359 (≠ I119) to F: in ARSEGS; loss of over 80% of tyrosine 3-monooxygenase activity; dbSNP:rs121917765
F375 (= F135) to L: in ARSEGS; loss of over 80% of tyrosine 3-monooxygenase activity; shifted substrate specificity from tyrosine to phenylalanine and Dopa; dbSNP:rs763198914
A376 (= A136) to V: in ARSEGS; loss of over 80% of tyrosine 3-monooxygenase activity
L387 (= L147) to M: in ARSEGS; no effect on tyrosine 3-monooxygenase activity
I394 (≠ R154) to T: in ARSEGS; complete loss of tyrosine 3-monooxygenase activity
T399 (≠ R159) to M: in ARSEGS; loss of over 80% of tyrosine 3-monooxygenase activity; dbSNP:rs1057520384
Q412 (≠ T172) to K: in ARSEGS; loss of over 80% of tyrosine 3-monooxygenase activity; reduced affinity for L-tyrosine; dbSNP:rs121917762
G414 (≠ Q174) to R: in ARSEGS; loss of over 80% of tyrosine 3-monooxygenase activity; dbSNP:rs370962049
G428 (≠ K188) to R: in ARSEGS; phenotype with prominent levodopa-responsive myoconus-dystonia (M-D); dbSNP:rs1264884607
R441 (≠ Q201) to P: in ARSEGS; complete loss of tyrosine 3-monooxygenase activity; dbSNP:rs367874223

Sites not aligning to the query:

19 modified: Phosphoserine; by CaMK2; S → C: found in a patient with ARSEGS; unknown pathological significance; dbSNP:rs766704202
62 modified: Phosphoserine; S→A: Affects subcellular localization. Accumulates mainly in the soma of the neuroblastoma cells.; S→E: Does not affect subcellular localization. Distributed throughout the soma and neurites.
71 modified: Phosphoserine; by CaMK2 and PKA; S→E: Suppresses feedback inhibition induced by dopamine. Suppresses feedback inhibition induced by dopamine; when associated with A-207.
112 V → M: in dbSNP:rs6356
207 C → Y: in ARSEGS; loss of over 80% of tyrosine 3-monooxygenase activity; C→A: Suppresses the decrease in tyrosine 3-monooxygenase activity induced by NEM modification. Suppresses feedback inhibition induced by dopamine; when associated with E-71.
227 D → G: in ARSEGS; complete loss of tyrosine 3-monooxygenase activity
233 R → H: in ARSEGS; loss of over 80% of tyrosine 3-monooxygenase activity; shifted substrate specificity from tyrosine to phenylalanine and Dopa; dbSNP:rs80338892
236 L → P: in ARSEGS; severe parkinsonian symptoms in early infancy; strongly reduced stability and tyrosine 3-monooxygenase activity; rare mutation; dbSNP:rs121917763
241 A → T: in ARSEGS; loss of over 80% of tyrosine 3-monooxygenase activity; dbSNP:rs1260455415
246 H → Y: in ARSEGS; loss of about 40% of tyrosine 3-monooxygenase activity
247 G → S: in ARSEGS; loss of about 50% of tyrosine 3-monooxygenase activity; shifted substrate specificity from tyrosine to phenylalanine and Dopa; dbSNP:rs762304556
467 S → G: in ARSEGS; loss of over 80% of tyrosine 3-monooxygenase activity
492 P → L: in ARSEGS; complete loss of tyrosine 3-monooxygenase activity; dbSNP:rs767635052
494 T → M: in ARSEGS; parkinsonian symptoms in infancy; no effect on tyrosine 3-monooxygenase activity; dbSNP:rs45471299
498 D → G: in ARSEGS; loss of over 80% of tyrosine 3-monooxygenase activity; dbSNP:rs771351747
499 V → M: in dbSNP:rs1800033
510 L → Q: in ARSEGS; complete loss of tyrosine 3-monooxygenase activity

P90986 Tyrosine 3-monooxygenase; Abnormal catecholamine distribution protein 2; Tyrosine 3-hydroxylase; TH; EC 1.14.16.2 from Caenorhabditis elegans (see 4 papers)
33% identity, 83% coverage: 12:228/263 of query aligns to 234:454/519 of P90986

query
sites
P90986

D

D

A

E

Q

I

G

G

F

Y

I

V

H

D

Y

Y

T

T

A

E

E

E

H

H

A

A

V

T

W

W

N

K

T

A

L

V

I

Y

T

E

R

K

Q

L

L

G

K

D

V

L

L

H

E

L

G

S

R

H

A

T

C

C

Q

A

E

V

Y

Y

M

R

D

Q

G

N

I

L

-

K

-

I

-

L

-
x
Q

E
|
E

K
x
E

L
x
K

G
x
V

L
|
L

P
x
T

H
x
A

D
|
D

R
|
R

I
|
I

P
|
P

Q
|
Q

L
x
I

D
x
R

E
x
D

I
x
V

N
|
N

K
|
K

V
x
F

L
|
L

G
x
Q

E
x
K

T
x
K

T
|
T

G
|
G

W
x
F

Q
x
E

V
x
L

A
x
R

R
x
P

V
x
C

P
x
S

A
x
G

L
|
L

I
x
L

P
x
S

F
x
A

Q
x
R

T
x
D

F
|
F

F
x
L

E
x
A

L
x
S

L
|
L

A
|
A

S
x
F

K
x
R

Q
x
V

F
|
F

P
x
Q

V
x
T

A
x
T

T
|
T

F
x
Y

I
x
L

R
|
R

T
x
H

R
x
H

E
x
K

E
x
S

L
x
P

D
x
H

Y
x
H

L
x
S

Q
x
P

E
|
E

P
|
P

D
|
D

I
x
L

F
x
I

H
|
H

E
|
E

I
x
L

F
x
L

G
|
G

H
|
H

C
x
V

P
|
P

L
x
M

L
x
F

T
x
S

N
x
D

P
|
P

W
x
L

F
x
L

A
|
A

E
x
Q

F
x
M

T
x
S

H
x
Q

T
x
D

Y
x
I

G
|
G

K
x
L

L
x
M

G
x
S

L
|
L

Q
x
G

A
|
A

S
|
S

K
x
D

E
|
E

E
x
H

R
x
I

V
x
E

Y
x
K

L
|
L

A
x
S

R
x
T

L
x
V

Y
|
Y

W
|
W

M
x
F

T
x
I

I
x
V

E
|
E

F
|
F

G
|
G

L
|
L

V
x
C

D
x
K

T
x
E

P
x
D

Q
x
G

G
x
K

K
x
L

R
x
K

I
x
A

Y
x
I

G
|
G

G
x
A

G
|
G

I
x
L

L
|
L

S
|
S

S
x
A

P
x
Y

K
x
G

E
|
E

T
x
L

V
x
M

Y
x
H

S
x
A

L
x
C

S
|
S

G
x
D

E
x
A

P
|
P

E
|
E

H
|
H

Q
x
K

A
x
D

F
|
F

D
|
D

P
|
P

L
x
A

E
x
V

A
x
T

M
x
A

R
x
V

T
x
Q

P
x
K

Y
|
Y

R
x
E

I
x
D

D
|
D

I
x
D

L
x
Y

Q
|
Q

P
|
P

L
|
L

Y
|
Y

F
|
F

V
|
V

L
x
A

P
x
D

N
x
S

L
x
I

Sites not aligning to the query:

35 modified: Phosphoserine; by PKA
276:519 mutation Missing: In e1112; spontaneously induces activation of the crh-1/CREB1 transcription factor in cholinergic SIA neurons in the absence and presence of food. Reduces swimming-induced paralysis in response to amphetamine. Defective male mating behavior.

5jk8A Phenylalanine hydroxylase from dictyostelium - bh2, norleucine complex
35% identity, 81% coverage: 17:230/263 of query aligns to 142:359/390 of 5jk8A

query
sites
5jk8A

I

I

H

D

Y

Y

T

T

A

E

E

E

H

I

A

K

V

T

W

W

N

G

T

V

L

V

I

Y

T

N

R

R

Q

L

L

K

K

E

V

L

L

F

E

P

G

T

R

N

A

A

C

C

Q

H

E

Q

Y

H

M

A

D

Y

G

I

I

F

-

P

-

L

-

E

E

Q

K

N

L

C

G

G

L

Y

P

S

H

P

D

D

R

N

I

I

P

P

Q

Q

L

L

D

Q

E

D

I

I

N

S

K

N

V

F

L

L

G

Q

E

E

T

C

T
|
T

G

G

W

W

Q

R

V

I

A

R

R

P

V

V

P

Q

A

G

L

L

I
x
L

P

S

F
x
A

Q

R

T

D

F
|
F

F

L

E

N

L

G

L

L

A

A

S

F

K
x
R

Q

V

F

F

P

H

V

A

A

T

T

Q

F

Y

I

I

R

R

T

H

R

P

E

S

E

V

L

P

D

L

Y
|
Y

L
x
T

Q

P

E

E

P

P

D

D

I

C

F

C

H
|
H

E

E

I

L

F

L

G

G

H
|
H

C

V

P

P

L

L

T

A

N

D

P

P

W

D

F

F

A

A

E
x
D

F

F

T

S

H

Q

T

E

Y

I

G

G

K

L

L

A

G

S

L

I

Q

G

A

A

S

S

K

D

E

E

E

D

R

I

V

Q

Y

L

L

L

A
x
S

R

T

L

C

Y
|
Y

W

W

M

F

T

T

I

V

E
|
E

F

F

G

G

L

L

V

C

D

K

T

E

P

G

Q

D

G

T

K

I

R

R

I

A

Y

Y

G

G

G

A

G

G

I

I

L

L

S
|
S

P

T

K

G

E

E

T

M

V

E

Y

H

S

F

L

L

S

T

G

D

E

K

P

A

E

K

H

K

Q

L

A

P

F

F

D

N

P

P

L

F

E

D

A

A

M

C

R

N

T

T

P

E

Y

Y

R

P

I

I

D

T

I

T

L

F

Q

Q

P

P

L

L

Y

Y

F

Y

V

V

L

A

P

E

N

S

L

F

K

Q

R

K

active site: H250 (= H121), H255 (= H126), E295 (= E166), S314 (= S185)
binding fe (iii) ion: H250 (= H121), H255 (= H126), E295 (= E166)
binding 7,8-dihydrobiopterin: L214 (≠ I85), A216 (≠ F87), F219 (= F90), S287 (≠ A158), Y290 (= Y161)
binding norleucine: Y242 (= Y113), T243 (≠ L114), H250 (= H121), S314 (= S185), S315 (= S186)
binding piperazine-n,n'-bis(2-ethanesulfonic acid): T203 (= T74), R226 (≠ K97), D266 (≠ E137)

Sites not aligning to the query:

binding piperazine-n,n'-bis(2-ethanesulfonic acid): 44, 365, 382

5jk5A Phenylalanine hydroxylase from dictyostelium - bh2 complex
35% identity, 81% coverage: 17:230/263 of query aligns to 151:368/400 of 5jk5A

query
sites
5jk5A

I

I

H

D

Y

Y

T

T

A

E

E

E

H

I

A

K

V

T

W

W

N

G

T

V

L

V

I

Y

T

N

R

R

Q

L

L

K

K

E

V

L

L

F

E

P

G

T

R

N

A

A

C

C

Q

H

E

Q

Y

H

M

A

D

Y

G

I

I

F

-

P

-

L

-

E

E

Q

K

N

L

C

G

G

L

Y

P

S

H

P

D

D

R

N

I

I

P

P

Q

Q

L

L

D

Q

E

D

I

I

N

S

K

N

V

F

L

L

G

Q

E

E

T

C

T
|
T

G

G

W

W

Q

R

V

I

A

R

R

P

V

V

P

Q

A
x
G

L
|
L

I
x
L

P

S

F

A

Q

R

T

D

F
|
F

F
x
L

E

N

L

G

L

L

A

A

S

F

K

R

Q

V

F

F

P

H

V

A

A

T

T

Q

F

Y

I

I

R

R

T

H

R

P

E

S

E

V

L

P

D

L

Y

Y

L

T

Q

P

E

E

P

P

D

D

I

C

F

C

H
|
H

E

E

I

L

F

L

G

G

H
|
H

C

V

P

P

L

L

T

A

N

D

P
|
P

W

D

F

F

A

A

E
x
D

F

F

T

S

H

Q

T

E

Y

I

G

G

K

L

L

A

G

S

L

I

Q

G

A

A

S

S

K

D

E

E

E

D

R

I

V

Q

Y

L

L

L

A
x
S

R

T

L

C

Y
|
Y

W

W

M

F

T

T

I

V

E
|
E

F

F

G

G

L

L

V

C

D

K

T

E

P

G

Q

D

G

T

K

I

R

R

I

A

Y

Y

G

G

G

A

G

G

I

I

L

L

S
|
S

S

S

P

T

K

G

E

E

T

M

V

E

Y

H

S

F

L

L

S

T

G

D

E

K

P

A

E

K

H

K

Q

L

A

P

F

F

D

N

P

P

L

F

E

D

A

A

M

C

R

N

T

T

P

E

Y

Y

R

P

I

I

D

T

I

T

L

F

Q

Q

P

P

L

L

Y

Y

F

Y

V

V

L

A

P

E

N

S

L

F

K

Q

R

K

active site: H259 (= H121), H264 (= H126), E304 (= E166), S323 (= S185)
binding fe (iii) ion: H259 (= H121), H264 (= H126), E304 (= E166)
binding 7,8-dihydrobiopterin: G221 (≠ A83), L222 (= L84), L223 (≠ I85), F228 (= F90), L229 (≠ F91), S296 (≠ A158), Y299 (= Y161)
binding piperazine-n,n'-bis(2-ethanesulfonic acid): T212 (= T74), P271 (= P133), D275 (≠ E137)

Sites not aligning to the query:

binding piperazine-n,n'-bis(2-ethanesulfonic acid): 374

P70080 Tryptophan 5-hydroxylase 1; Tryptophan 5-monooxygenase 1; EC 1.14.16.4 from Gallus gallus (Chicken) (see paper)
36% identity, 79% coverage: 17:224/263 of query aligns to 165:376/445 of P70080

query
sites
P70080

I

I

H

E

Y

F

T

T

A

E

E

E

H

I

A

K

V

T

W

W

N

G

T

T

L

V

I

Y

T

R

R

E

Q

L

L

N

K

K

V

L

L

Y

E

P

G

T

R

H

A

A

C

C

Q

R

E

E

Y

Y

M

L

D

K

G

N

I

L

E

P

K

L

L

L

-

T

-

K

-

Y

-

C

G

G

L

Y

P

R

H

E

D

D

R

N

I

I

P

P

Q

Q

L

L

D

E

E

D

I

V

N

S

K

R

V

F

L

L

G

K

E

E

T

R

T

T

G

G

W

F

Q

T

V

I

A

R

R

P

V

V

P

A

A

G

L
x
Y

I

L

P

S

F

P

Q

R

T

D

F

F

F

L

E

A

L

G

L

L

A

A

S

F

K

R

Q

V

F

F

P

H

V

C

A

T

T

Q

F

Y

I

V

R
|
R

T

H

R

S

E

S

E

D

L

P

D

L

Y

Y

L
x
T

Q

P

E

E

P

P

D

D

I

T

F

C

H
|
H

E

E

I

L

F

L

G

G

H
|
H

C

V

P

P

L

L

T

A

N

E

P

P

W

S

F

F

A

A

E

Q

F

F

T

S

H

Q

T

E

Y

I

G

G

K

L

L

A

G

S

L

L

Q

G

A

A

S

S

K

D

E

E

E

A

R

V

V

Q

Y

K

L

L

A

A

R

T

L

C

Y

Y

W

F

M

F

T

T

I

V

E
|
E

F

F

G

G

L

L

V

C

D

K

T

Q

P

E

Q

G

G

Q

K

L

R

R

I

V

Y

Y

G

G

G

A

G

G

I

L

L

L

S
|
S

S

S

P

I

K

S

E

E

T

L

V

K

Y

H

S

S

L

L

S

S

G

G

E

S

P

A

E

K

H

V

Q

K

A

P

F

F

D

D

P

P

L

K

E

V

A

T

M

C

R

K

T

Q

P

E

Y

C

R

L

I
|
I

D

T

I

T

L

F

Q

Q

P

E

L

V

Y

Y

F

F

V

V

Y236 (≠ L84) binding
R258 (= R106) binding
T266 (≠ L114) binding
H273 (= H121) binding
H278 (= H126) binding
E318 (= E166) binding
S337 (= S185) binding
I367 (= I215) binding

3e2tA The catalytic domain of chicken tryptophan hydroxylase 1 with bound tryptophan (see paper)
36% identity, 79% coverage: 17:224/263 of query aligns to 61:272/307 of 3e2tA

query
sites
3e2tA

I

I

H

E

Y

F

T

T

A

E

E

E

H

I

A

K

V

T

W

W

N

G

T

T

L

V

I

Y

T

R

R

E

Q

L

L

N

K

K

V

L

L

Y

E

P

G

T

R

H

A

A

C

C

Q

R

E

E

Y

Y

M

L

D

K

G

N

I

L

E

P

K

L

L

L

-

T

-

K

-

Y

-

C

G

G

L

Y

P

R

H

E

D

D

R

N

I

I

P

P

Q

Q

L

L

D

E

E

D

I

V

N

S

K

R

V

F

L

L

G

K

E

E

T

R

T

T

G

G

W

F

Q

T

V

I

A

R

R

P

V

V

P

A

A

G

L

Y

I

L

P

S

F

P

Q

R

T

D

F

F

F

L

E

A

L

G

L

L

A

A

S

F

K

R

Q

V

F

F

P

H

V

C

A

T

T

Q

F

Y

I

V

R
|
R

T

H

R

S

E

S

E

D

L

P

D

L

Y
|
Y

L
x
T

Q

P

E
|
E

P
|
P

D

D

I

T

F

C

H
|
H

E

E

I

L

F

L

G

G

H
|
H

C

V

P

P

L

L

T

A

N

E

P

P

W

S

F

F

A

A

E

Q

F

F

T

S

H

Q

T

E

Y

I

G

G

K

L

L

A

G

S

L

L

Q

G

A

A

S

S

K

D

E

E

E

A

R

V

V

Q

Y

K

L

L

A

A

R

T

L

C

Y

Y

W

F

M

F

T

T

I

V

E
|
E

F
|
F

G

G

L

L

V

C

D

K

T

Q

P

E

Q

G

G

Q

K

L

R

R

I

V

Y

Y

G

G

G

A

G

G

I

L

L

L

S
|
S

S

S

P

I

K

S

E

E

T

L

V

K

Y

H

S

S

L

L

S

S

G

G

E

S

P

A

E

K

H

V

Q

K

A

P

F

F

D

D

P

P

L

K

E

V

A

T

M

C

R

K

T

Q

P

E

Y

C

R

L

I
|
I

D

T

I

T

L

F

Q

Q

P

E

L

V

Y

Y

F

F

V

V

active site: H169 (= H121), H174 (= H126), E214 (= E166), S233 (= S185)
binding fe (iii) ion: H169 (= H121), H174 (= H126), E214 (= E166)
binding imidazole: H169 (= H121), H174 (= H126), E214 (= E166)
binding tryptophan: R154 (= R106), Y161 (= Y113), T162 (≠ L114), E164 (= E116), P165 (= P117), H169 (= H121), F215 (= F167), S233 (= S185), I263 (= I215)

7zifA Crystal structure of human tryptophan hydroxylase 1 in complex with inhibitor km-480 (see paper)
34% identity, 79% coverage: 17:224/263 of query aligns to 61:272/291 of 7zifA

query
sites
7zifA

I

V

H

E

Y

F

T

T

A

E

E

E

H

I

A

K

V

T

W

W

N

G

T

T

L

V

I

F

T

Q

R

E

Q

L

L

N

K

K

V

L

L

Y

E

P

G

T

R

H

A

A

C

C

Q

R

E

E

Y

Y

M

L

D

K

G

N

I

L

E

P

K

L

L

L

-

S

-

K

-

Y

-

C

G

G

L

Y

P

R

H

E

D

D

R

N

I

I

P

P

Q

Q

L

L

D

E

E

D

I

V

N

S

K

N

V

F

L

L

G

K

E

E

T

R

T

T

G

G

W

F

Q

S

V

I

A

R

R

P

V

V

P

A

A

G

L
x
Y

I
x
L

P

S

F
x
P

Q

R

T

D

F
|
F

F

L

E

S

L

G

L

L

A

A

S

F

K

R

Q

V

F

F

P

H

V

C

A

T

T

Q

F

Y

I

V

R

R

T

H

R

S

E

S

E

D

L

P

D

F

Y
|
Y

L
x
T

Q

P

E

E

P
|
P

D

D

I

T

F

C

H
|
H

E

E

I

L

F

L

G

G

H
|
H

C

V

P

P

L

L

T

A

N

E

P

P

W

S

F

F

A

A

E

Q

F

F

T

S

H

Q

T

E

Y

I

G

G

K

L

L

A

G

S

L

L

Q

G

A

A

S

S

K

E

E

E

E

A

R

V

V

Q

Y

K

L

L

A

A

R

T

L

C

Y

Y

W

F

M

F

T

T

I

V

E
|
E

F

F

G

G

L

L

V

C

D

K

T

Q

P

D

Q

G

G

Q

K

L

R

R

I

V

Y

F

G

G

G

A

G

G

I

L

L

L

S

S

P

I

K

S

E

E

T

L

V

K

Y

H

S

A

L

L

S

S

G

G

E

H

P

A

E

K

H

V

Q

K

A

P

F

F

D

D

P

P

L

K

E

I

A

T

M

C

R

K

T

Q

P

E

Y

C

R

L

I

I

D

T

I

T

L

F

Q

Q

P

D

L

V

Y

Y

F

F

V

V

binding fe (iii) ion: H169 (= H121), H174 (= H126), E214 (= E166)
binding (2R)-2-azanyl-5-[[2-[3-methyl-2,6-bis(oxidanylidene)-7-(phenylmethyl)purin-8-yl]sulfanyl-3H-benzimidazol-5-yl]amino]-5-oxidanylidene-pentanoic acid: Y132 (≠ L84), L133 (≠ I85), P135 (≠ F87), F138 (= F90), Y161 (= Y113), T162 (≠ L114), P165 (= P117), H169 (= H121), E214 (= E166)

1mlwA Crystal structure of human tryptophan hydroxylase with bound 7,8-dihydro-l-biopterin cofactor and fe(iii) (see paper)
34% identity, 79% coverage: 17:224/263 of query aligns to 61:272/290 of 1mlwA

query
sites
1mlwA

I

V

H

E

Y

F

T

T

A

E

E

E

H

I

A

K

V

T

W

W

N

G

T

T

L

V

I

F

T

R

R

E

Q

L

L

N

K

K

V

L

L

Y

E

P

G

T

R

H

A

A

C

C

Q

R

E

E

Y

Y

M

L

D

K

G

N

I

L

E

P

K

L

L

L

-

S

-

K

-

Y

-

C

G

G

L

Y

P

R

H

E

D

D

R

N

I

I

P

P

Q

Q

L

L

D

E

E

D

I

V

N

S

K

N

V

F

L

L

G

K

E

E

T

R

T

T

G

G

W

F

Q

S

V

I

A

R

R

P

V

V

P

A

A

G

L
x
Y

I
x
L

P

S

F
x
P

Q

R

T

D

F
|
F

F

L

E

S

L

G

L

L

A

A

S

F

K

R

Q

V

F

F

P

H

V

C

A

T

T

Q

F

Y

I

V

R

R

T

H

R

S

E

S

E

D

L

P

D

F

Y

Y

L

T

Q

P

E

E

P

P

D

D

I

T

F

C

H
|
H

E

E

I

L

F

L

G

G

H
|
H

C

V