2pah
From Proteopedia
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==Overview== | ==Overview== | ||
| - | Phenylalanine hydroxylase (PheOH) catalyzes the conversion of | + | 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== | ==Disease== | ||
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[[Category: Erlandsen, H.]] | [[Category: Erlandsen, H.]] | ||
[[Category: Fusetti, F.]] | [[Category: Fusetti, F.]] | ||
| - | [[Category: Stevens, R | + | [[Category: Stevens, R C.]] |
[[Category: FE]] | [[Category: FE]] | ||
[[Category: hydroxylase]] | [[Category: hydroxylase]] | ||
[[Category: phenylketonuria]] | [[Category: phenylketonuria]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 18:27:46 2008'' |
Revision as of 16:27, 21 February 2008
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TETRAMERIC HUMAN PHENYLALANINE HYDROXYLASE
Contents |
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
Page seeded by OCA on Thu Feb 21 18:27:46 2008
