X-ray Crystal Structure of Arsenite-Inhibited Xanthine Oxidase:[mu]-Sulfido,[mu]-Oxo Double Bridge between Molybdenum and Arsenic in the Active Site
- UCR
Xanthine oxidoreductase is a molybdenum-containing enzyme that catalyzes the hydroxylation reaction of sp{sup 2}-hybridized carbon centers of a variety of substrates, including purines, aldehydes, and other heterocyclic compounds. The complex of arsenite-inhibited xanthine oxidase has been characterized previously by UV-vis, electron paramagnetic resonance, and X-ray absorption spectroscopy (XAS), and the catalytically essential sulfido ligand of the square-pyrimidal molybdenum center has been suggested to be involved in arsenite binding through either a {mu}-sulfido,{mu}-oxo double bridge or a single {mu}-sulfido bridge. However, this is contrary to the crystallographically observed single {mu}-oxo bridge between molybdenum and arsenic in the desulfo form of aldehyde oxidoreductase from Desulfovibrio gigas (an enzyme closely related to xanthine oxidase), whose molybdenum center has an oxo ligand replacing the catalytically essential sulfur, as seen in the functional form of xanthine oxidase. Here we use X-ray crystallography to characterize the molybdenum center of arsenite-inhibited xanthine oxidase and solve the structures of the oxidized and reduced inhibition complexes at 1.82 and 2.11 {angstrom} resolution, respectively. We observe {mu}-sulfido,{mu}-oxo double bridges between molybdenum and arsenic in the active sites of both complexes. Arsenic is four-coordinate with a distorted trigonal-pyramidal geometry in the oxidized complex and three-coordinate with a distorted trigonal-planar geometry in the reduced complex. The doubly bridged binding mode is in agreement with previous XAS data indicating that the catalytically essential sulfur is also essential for the high affinity of reduced xanthine oxidoreductase for arsenite.
- Research Organization:
- Argonne National Lab. (ANL), Argonne, IL (United States). Advanced Photon Source (APS)
- Sponsoring Organization:
- National Institutes of Health (NIH)
- OSTI ID:
- 1050076
- Journal Information:
- J. Am. Chem. Soc., Vol. 133, Issue (32) ; 08, 2011; ISSN 0002-7863
- Country of Publication:
- United States
- Language:
- ENGLISH
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Related Subjects
60 APPLIED LIFE SCIENCES
ABSORPTION SPECTROSCOPY
AFFINITY
ALDEHYDES
ARSENIC
CARBON
CRYSTAL STRUCTURE
CRYSTALLOGRAPHY
DESULFOVIBRIO
ELECTRON SPIN RESONANCE
ENZYMES
FUNCTIONALS
GEOMETRY
HETEROCYCLIC COMPOUNDS
HYDROXYLATION
MOLYBDENUM
OXIDASES
OXIDOREDUCTASES
PURINES
RESOLUTION
SUBSTRATES
SULFUR
XANTHINES