Crystal structures of bovine milk xanthine dehydrogenase and xanthine oxidase: Structure-based mechanism of conversion

• DOI: 10.1073/pnas.97.20.10723
• Publication Date: 2002-07-26T14:32:33Z
• Authors: Cristofer Enroth; Bryan T. Eger; Ken Okamoto; Tomoko Nishino; Takeshi Nishino; Emil F. Pai
• Keywords: Xanthine dehydrogenase; Flavin adenine dinucleotide; Xanthine; Flavoprotein; Hypoxanthine

Mammalian xanthine oxidoreductases, which catalyze the last two steps in formation of urate, are synthesized as dehydrogenase form (XDH) but can be readily converted to oxidase (XO) by oxidation sulfhydryl residues or proteolysis. Here, we present crystal structure dimeric ( M r , 290,000) bovine milk XDH at 2.1-Å resolution and XO 2.5-Å describe major changes that occur on proteolytic transformation form. Each molecule is composed an N-terminal 20-kDa domain containing iron sulfur centers, a central 40-kDa flavin adenine dinucleotide domain, C-terminal 85-kDa molybdopterin-binding with four redox centers aligned almost linear fashion. Cleavage surface-exposed loops causes structural rearrangement another loop close ring (Gln 423—Lys 433). This movement partially blocks access NAD substrate cofactor electrostatic environment active site, reflecting switch specificity observed for forms this enzyme.