3NVV

Crystal Structure of Bovine Xanthine Oxidase in Complex with Arsenite

Summary for 3NVV

• Entry DOI: 10.2210/pdb3nvv/pdb
• Related: 3NVW 3NVY 3NVZ
• Descriptor: Xanthine dehydrogenase/oxidase, FE2/S2 (INORGANIC) CLUSTER, FLAVIN-ADENINE DINUCLEOTIDE, ... (9 entities in total)
• Functional Keywords: hydroxylase, homodimer, xanthine oxidase, arsenite, oxidoreductase
• Biological source: Bos taurus (bovine,cow,domestic cattle,domestic cow); More
• Cellular location: Cytoplasm (By similarity): P80457 P80457 P80457
• Total number of polymer chains: 6
• Total formula weight: 280434.14

Authors

Cao, H.,Hille, R. (deposition date: 2010-07-08, release date: 2011-01-19, Last modification date: 2012-05-09)

Primary citation

Cao, H.,Hall, J.,Hille, R.
X-ray Crystal Structure of Arsenite-Inhibited Xanthine Oxidase: Mu-Sulfido,Mu-Oxo Double Bridge between Molybdenum and Arsenic in the Active Site.
J.Am.Chem.Soc., 133:12414-12417, 2011

PubMed Abstract: Xanthine oxidoreductase is a molybdenum-containing enzyme that catalyzes the hydroxylation reaction of sp(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 μ-sulfido,μ-oxo double bridge or a single μ-sulfido bridge. However, this is contrary to the crystallographically observed single μ-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 Å resolution, respectively. We observe μ-sulfido,μ-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.

PubMed: 21761899
DOI: 10.1021/ja2050265

Experimental method

X-RAY DIFFRACTION (1.82 Å)