Substrate Orientation and Catalysis at the Molybdenum Site in Xanthine Oxidase: CRYSTAL STRUCTURES IN COMPLEX WITH XANTHINE AND LUMAZINE.

TitleSubstrate Orientation and Catalysis at the Molybdenum Site in Xanthine Oxidase: CRYSTAL STRUCTURES IN COMPLEX WITH XANTHINE AND LUMAZINE.
Publication TypeJournal Article
Year of Publication2009
AuthorsPauff, JM, Cao H, Hille R
JournalThe Journal of biological chemistry
Volume284
Pagination8760-7
Date Published2009 Mar 27
Abstract

Xanthine oxidoreductase is a ubiquitous cytoplasmic protein that catalyzes the final two steps in purine catabolism. We have previously investigated the catalytic mechanism of the enzyme by rapid reaction kinetics and x-ray crystallography using the poor substrate 2-hydroxy-6-methylpurine, focusing our attention on the orientation of substrate in the active site and the role of Arg-880 in catalysis. Here we report additional crystal structures of as-isolated, functional xanthine oxidase in the course of reaction with the pterin substrate lumazine at 2.2 A resolution and of the nonfunctional desulfo form of the enzyme in complex with xanthine at 2.6 A resolution. In both cases the orientation of substrate is such that the pyrimidine subnucleus is oriented opposite to that seen with the slow substrate 2-hydroxy-6-methylpurine. The mechanistic implications as to how the ensemble of active site functional groups in the active site work to accelerate reaction rate are discussed.

10.1074/jbc.M804517200
Pub Med Link

http://www.ncbi.nlm.nih.gov/pubmed/19109252?dopt=Abstract

Alternate JournalJ. Biol. Chem.
Citekey19109252