2PAH

TETRAMERIC HUMAN PHENYLALANINE HYDROXYLASE


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 3.10 Å
  • R-Value Free: 0.326 
  • R-Value Work: 0.251 
  • R-Value Observed: 0.251 

wwPDB Validation   3D Report Full Report


This is version 1.3 of the entry. See complete history


Literature

Structure of tetrameric human phenylalanine hydroxylase and its implications for phenylketonuria.

Fusetti, F.Erlandsen, H.Flatmark, T.Stevens, R.C.

(1998) J Biol Chem 273: 16962-16967

  • DOI: https://doi.org/10.1074/jbc.273.27.16962
  • Primary Citation of Related Structures:  
    2PAH

  • PubMed Abstract: 

    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.


  • Organizational Affiliation

    Department of Chemistry, University of California and Physical Biosciences Division, Lawrence Berkeley National Laboratory, Berkeley, California 94720, USA.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
PROTEIN (PHENYLALANINE HYDROXYLASE)
A, B
335Homo sapiensMutation(s): 0 
EC: 1.14.16.1
UniProt & NIH Common Fund Data Resources
Find proteins for P00439 (Homo sapiens)
Explore P00439 
Go to UniProtKB:  P00439
PHAROS:  P00439
GTEx:  ENSG00000171759 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP00439
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 3.10 Å
  • R-Value Free: 0.326 
  • R-Value Work: 0.251 
  • R-Value Observed: 0.251 
  • Space Group: P 31 1 2
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 119.5α = 90
b = 119.5β = 90
c = 126γ = 120
Software Package:
Software NamePurpose
AMoREphasing
X-PLORrefinement
DENZOdata reduction
SCALEPACKdata scaling

Structure Validation

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Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 1999-10-06
    Type: Initial release
  • Version 1.1: 2007-10-16
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Derived calculations, Version format compliance
  • Version 1.3: 2023-08-30
    Changes: Data collection, Database references, Derived calculations, Refinement description