We found a match
Your institution may have rights to this item. Sign in to continue.
- Title
Crystal structure of human homogentisate dioxygenase.
- Authors
Titus, Greg P.; Mueller, Heather A.; Burgner, John; Rodríguez de Córdoba, Santiago; Peñalva, Miguel A.; Timm, David E.
- 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 Å 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.
- Subjects
DISEASES; IRON ions; DIMERS; BINDING sites; GENETIC mutation
- Publication
Nature Structural Biology, 2000, Vol 7, Issue 7, p542
- ISSN
1072-8368
- Publication type
Article