PDBsum entry 3e2t

Oxidoreductase

PDB id: 3e2t

Contents

Protein chain

307 a.a. *

Ligands

SO4

IMD

TRP

PGE ×2

Metals

_FE

Waters ×219

* Residue conservation analysis

PDB id:

3e2t

Name:

Oxidoreductase

Title:

The catalytic domain of chicken tryptophan hydroxylase 1 with bound tryptophan

Structure:

Tryptophan 5-hydroxylase 1. Chain: a. Fragment: catalytic domain, unp residues 101-414. Synonym: tryptophan 5-monooxygenase 1. Engineered: yes

Source:

Gallus gallus. Bantam,chickens. Organism_taxid: 9031. Strain: white leghorn. Expressed in: escherichia coli. Expression_system_taxid: 562.

Resolution:

1.90Å R-factor: 0.184 R-free: 0.226

Authors:

M.S.Windahl,C.R.Petersen,H.E.C.Christensen,P.Harris

Key ref:

M.S.Windahl et al. (2008). Crystal structure of tryptophan hydroxylase with bound amino acid substrate. Biochemistry, 47, 12087-12094. PubMed id: 18937498

Date:

06-Aug-08 Release date: 04-Nov-08

Protein chain

P70080  (TPH1_CHICK) -  Tryptophan 5-hydroxylase 1 from Gallus gallus

Seq: 445 a.a.

Struc: 307 a.a.

Enzyme reactions

• Enzyme class: E.C.1.14.16.4 - tryptophan 5-monooxygenase.
• Pathway: Biopterin Biosynthesis
• Reaction: (6R)-L-erythro-5,6,7,8-tetrahydrobiopterin + L-tryptophan + O2 = 5-hydroxy-L-tryptophan + (4aS,6R)-4a-hydroxy-L-erythro-5,6,7,8- tetrahydrobiopterin

(6R)-L-erythro-5,6,7,8-tetrahydrobiopterin + L-tryptophan (Bound ligand (Het Group name = TRP) corresponds exactly) + O2 = 5-hydroxy-L-tryptophan + (4aS,6R)-4a-hydroxy-L-erythro-5,6,7,8- tetrahydrobiopterin

• Cofactor: Fe cation

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

reference

Biochemistry 47:12087-12094 (2008)

PubMed id: 18937498

Crystal structure of tryptophan hydroxylase with bound amino acid substrate.

M.S.Windahl, C.R.Petersen, H.E.Christensen, P.Harris.

ABSTRACT

Tryptophan hydroxylase (TPH) is a mononuclear non-heme iron enzyme, which catalyzes the reaction between tryptophan, O 2, and tetrahydrobiopterin (BH 4) to produce 5-hydroxytryptophan and 4a-hydroxytetrahydrobiopterin. This is the first and rate-limiting step in the biosynthesis of the neurotransmitter and hormone serotonin (5-hydroxytryptamine). We have determined the 1.9 A resolution crystal structure of the catalytic domain (Delta1-100/Delta415-445) of chicken TPH isoform 1 (TPH1) in complex with the tryptophan substrate and an iron-bound imidazole. This is the first structure of any aromatic amino acid hydroxylase with bound natural amino acid substrate. The iron coordination can be described as distorted trigonal bipyramidal coordination with His273, His278, and Glu318 (partially bidentate) and one imidazole as ligands. The tryptophan stacks against Pro269 with a distance of 3.9 A between the iron and the tryptophan Czeta3 atom that is hydroxylated. The binding of tryptophan and maybe the imidazole has caused the structural changes in the catalytic domain compared to the structure of the human TPH1 without tryptophan. The structure of chicken TPH1 is more compact, and the loops of residues Leu124-Asp139 and Ile367-Thr369 close around the active site. Similar structural changes are seen in the catalytic domain of phenylalanine hydroxylase (PAH) upon binding of substrate analogues norleucine and thienylalanine to the PAH.BH 4 complex. In fact, the chicken TPH1.Trp.imidazole structure resembles the PAH.BH 4.thienylalanine structure more (root-mean-square deviation for Calpha atoms of 0.90 A) than the human TPH1 structure (root-mean-square deviation of 1.47 A).