Crystal structure of human homogentisate dioxygenase

Homogentisate dioxygenase (HGO) cleaves the aromatic ring during the metabo lic degradation of Phe and Tyr. HGO deficiency causes alkaptonuria (AKU), t he first human disease shown to be inherited as a recessive Mendelian trait . Crystal structures of apo-HGO and EIGO containing an iron ion have been d etermined at 1.9 and 2.3 Angstrom resolution, respectively. The HGO protome r, which contains a 280-residue N-terminal domain and a 140-residue C-termi nal domain, associates as a hexamer arranged as a dimer of trimers, The act ive 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 structur al dass of dioxygenases. The largest group of AKU associated missense mutat ions affect residues located in regions of contact between subunits.