2pah

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spinqualitylabelsall models 2pah, resolution 3.1Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

TETRAMERIC HUMAN PHENYLALANINE HYDROXYLASE

Contents 1 Overview 2 Disease 3 About this Structure 4 Reference

Overview

Phenylalanine hydroxylase (PheOH) catalyzes the conversion of, L-phenylalanine to L-tyrosine, the rate-limiting step in the oxidative, degradation of phenylalanine. Mutations in the human PheOH gene cause, phenylketonuria, a common autosomal recessive metabolic disorder that in, untreated patients often results in varying degrees of mental retardation., We have determined the crystal structure of human PheOH (residues, 118-452). The enzyme crystallizes as a tetramer with each monomer, consisting of a catalytic and a tetramerization domain. The, tetramerization domain is characterized by the presence of a domain, swapping arm that interacts with the other monomers forming an, antiparallel coiled-coil. The structure is the first report of a, tetrameric PheOH and displays an overall architecture similar to that of, the functionally related tyrosine hydroxylase. In contrast to the tyrosine, hydroxylase tetramer structure, a very pronounced asymmetry is observed in, the phenylalanine hydroxylase, caused by the occurrence of two alternate, conformations in the hinge region that leads to the coiled-coil helix., Examination of the mutations causing PKU shows that some of the most, frequent mutations are located at the interface of the catalytic and, tetramerization domains. Their effects on the structural and cellular, stability of the enzyme are discussed.

Disease

Known diseases associated with this structure: Hyperphenylalaninemia, mild OMIM:[261600], Phenylketonuria OMIM:[261600]

About this Structure

2PAH is a Single protein structure of sequence from Homo sapiens with as ligand. The following page contains interesting information on the relation of 2PAH with [Phenylalanine Hydroxylase]. Active as Phenylalanine 4-monooxygenase, with EC number 1.14.16.1 Known structural/functional Site: . Full crystallographic information is available from OCA.

Reference

Structure of tetrameric human phenylalanine hydroxylase and its implications for phenylketonuria., Fusetti F, Erlandsen H, Flatmark T, Stevens RC, J Biol Chem. 1998 Jul 3;273(27):16962-7. PMID:9642259

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