PDBsum entry 2mda

Oxidoreductase

PDB id: 2mda

Contents

Protein chains

95 a.a.

PDB id:

2mda

Name:

Oxidoreductase

Title:

The solution structure of the regulatory domain of tyrosine hydroxylase

Structure:

Tyrosine 3-monooxygenase. Chain: a, b. Fragment: regulatory domain (unp residues 65-159). Synonym: tyrosine 3-hydroxylase, th. Engineered: yes

Source:

Rattus norvegicus. Brown rat,rat,rats. Organism_taxid: 10116. Gene: th. Expressed in: escherichia coli. Expression_system_taxid: 562.

NMR struc:

10 models

Authors:

S.Zhang,T.Huang,A.Hinck,P.Fitzpatrick

Key ref:

S.Zhang et al. (2014). The solution structure of the regulatory domain of tyrosine hydroxylase. J Mol Biol, 426, 1483-1497. PubMed id: 24361276 DOI: 10.1016/j.jmb.2013.12.015

Date:

08-Sep-13 Release date: 01-Jan-14

Protein chains

P04177  (TY3H_RAT) -  Tyrosine 3-monooxygenase from Rattus norvegicus

Seq: 498 a.a.

Struc: 95 a.a.

Enzyme reactions

• Enzyme class: E.C.1.14.16.2 - tyrosine 3-monooxygenase.
• Pathway: Dopa Biosynthesis
• Reaction: (6R)-L-erythro-5,6,7,8-tetrahydrobiopterin + L-tyrosine + O2 = (4aS,6R)- 4a-hydroxy-L-erythro-5,6,7,8-tetrahydrobiopterin + L-dopa
• Cofactor: Fe cation

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

reference

DOI no: 10.1016/j.jmb.2013.12.015

J Mol Biol 426:1483-1497 (2014)

PubMed id: 24361276

The solution structure of the regulatory domain of tyrosine hydroxylase.

S.Zhang, T.Huang, U.Ilangovan, A.P.Hinck, P.F.Fitzpatrick.

ABSTRACT

Tyrosine hydroxylase (TyrH) catalyzes the hydroxylation of tyrosine to form 3,4-dihydroxyphenylalanine in the biosynthesis of the catecholamine neurotransmitters. The activity of the enzyme is regulated by phosphorylation of serine residues in a regulatory domain and by binding of catecholamines to the active site. Available structures of TyrH lack the regulatory domain, limiting the understanding of the effect of regulation on structure. We report the use of NMR spectroscopy to analyze the solution structure of the isolated regulatory domain of rat TyrH. The protein is composed of a largely unstructured N-terminal region (residues 1-71) and a well-folded C-terminal portion (residues 72-159). The structure of a truncated version of the regulatory domain containing residues 65-159 has been determined and establishes that it is an ACT domain. The isolated domain is a homodimer in solution, with the structure of each monomer very similar to that of the core of the regulatory domain of phenylalanine hydroxylase. Two TyrH regulatory domain monomers form an ACT domain dimer composed of a sheet of eight strands with four α-helices on one side of the sheet. Backbone dynamic analyses were carried out to characterize the conformational flexibility of TyrH65-159. The results provide molecular details critical for understanding the regulatory mechanism of TyrH.