Nature of the catalytically labile oxygen at the active site of xanthine oxidase

J Am Chem Soc. 2005 Mar 30;127(12):4518-22. doi: 10.1021/ja042500o.


In this paper we report the results of molybdenum K-edge X-ray absorption studies performed on the oxidized active site of xanthine oxidase at pH 6 and 10. These results indicate that the active site possesses one terminal oxygen ligand (Mo=O), two thiolate ligands (Mo-S), one terminal sulfido ligand (Mo=S), and one Mo-OH moiety. EXAFS analysis demonstrates that the Mo-OH bond shortens from 1.97 A at pH 6 to 1.75 A at pH 10, which is consistent with the generation of a Mo-O- moiety. This study provides convincing structural evidence that the catalytic oxygen donor at the oxidized active site of xanthine oxidase is Mo-OH rather than the Mo-OH2 ligation previously suggested by X-ray crystallography. These results support a mechanism initiated by base-assisted nucleophilic attack of the substrate by Mo-OH.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Binding Sites
  • Catalysis
  • Hydrogen-Ion Concentration
  • Molybdenum / chemistry
  • Oxygen / chemistry*
  • Oxygen / metabolism
  • Spectrometry, X-Ray Emission / methods
  • Xanthine Oxidase / chemistry*
  • Xanthine Oxidase / metabolism


  • Molybdenum
  • Xanthine Oxidase
  • Oxygen