Crystal structure of human homogentisate dioxygenase

Nat Struct Biol. 2000 Jul;7(7):542-6. doi: 10.1038/76756.

Abstract

Homogentisate dioxygenase (HGO) cleaves the aromatic ring during the metabolic degradation of Phe and Tyr. HGO deficiency causes alkaptonuria (AKU), the first human disease shown to be inherited as a recessive Mendelian trait. Crystal structures of apo-HGO and HGO containing an iron ion have been determined at 1.9 and 2.3 A resolution, respectively. The HGO protomer, which contains a 280-residue N-terminal domain and a 140-residue C-terminal domain, associates as a hexamer arranged as a dimer of trimers. The active site iron ion is coordinated near the interface between subunits in the HGO trimer by a Glu and two His side chains. HGO represents a new structural class of dioxygenases. The largest group of AKU associated missense mutations affect residues located in regions of contact between subunits.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Alkaptonuria / enzymology*
  • Alkaptonuria / genetics
  • Apoenzymes / chemistry
  • Apoenzymes / genetics
  • Apoenzymes / metabolism
  • Binding Sites
  • Catalysis
  • Crystallography, X-Ray
  • Dimerization
  • Dioxygenases*
  • Homogentisate 1,2-Dioxygenase
  • Humans
  • Iron / metabolism
  • Models, Molecular
  • Molecular Sequence Data
  • Oxygenases / chemistry*
  • Oxygenases / deficiency
  • Oxygenases / genetics
  • Oxygenases / metabolism
  • Protein Binding
  • Protein Structure, Quaternary
  • Protein Structure, Secondary
  • Structure-Activity Relationship

Substances

  • Apoenzymes
  • Iron
  • Oxygenases
  • Dioxygenases
  • Homogentisate 1,2-Dioxygenase

Associated data

  • PDB/1EY2
  • PDB/1EYB