Titus G P, Mueller H A, Burgner J, Rodríguez De Córdoba S, Peñalva M A, Timm D E
Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, 635 Barnhill Drive, Indianapolis, Indiana 46202, USA.
Nat Struct Biol. 2000 Jul;7(7):542-6. doi: 10.1038/76756.
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.
尿黑酸双加氧酶（HGO）在苯丙氨酸（Phe）和酪氨酸（Tyr）的代谢降解过程中裂解芳香环。HGO缺乏会导致黑尿症（AKU），这是首个被证明以隐性孟德尔性状遗传的人类疾病。分别在1.9埃和2.3埃分辨率下测定了脱辅基HGO和含有铁离子的HGO的晶体结构。HGO原体包含一个280个残基的N端结构域和一个140个残基的C端结构域，以三聚体二聚体形式排列的六聚体形式缔合。活性位点铁离子通过一个谷氨酸（Glu）和两条组氨酸（His）侧链在HGO三聚体亚基之间的界面附近配位。HGO代表了双加氧酶的一种新结构类别。与AKU相关的错义突变中最大的一组影响位于亚基之间接触区域的残基。
