期刊
JOURNAL OF BIOLOGICAL CHEMISTRY
卷 284, 期 13, 页码 8751-8758出版社
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
DOI: 10.1074/jbc.M804517200
关键词
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资金
- National Institutes of Health [GM 075036]
- United States Department of Energy, Office of Science, Office of Basic Energy Sciences [DE-AC02-06CH11357]
- SGX Pharmaceuticals, Inc.
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 angstrom resolution and of the nonfunctional desulfo form of the enzyme in complex with xanthine at 2.6 angstrom 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.
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