Crystal structures of the active and alloxanthine-inhibited forms of xanthine dehydrogenase from Rhodobacter capsulatus.

Journal Article (Journal Article)

Xanthine dehydrogenase (XDH), a complex molybdo/iron-sulfur/flavoprotein, catalyzes the oxidation of hypoxanthine to xanthine followed by oxidation of xanthine to uric acid with concomitant reduction of NAD+. The 2.7 A resolution structure of Rhodobacter capsulatus XDH reveals that the bacterial and bovine XDH have highly similar folds despite differences in subunit composition. The NAD+ binding pocket of the bacterial XDH resembles that of the dehydrogenase form of the bovine enzyme rather than that of the oxidase form, which reduces O(2) instead of NAD+. The drug allopurinol is used to treat XDH-catalyzed uric acid build-up occurring in gout or during cancer chemotherapy. As a hypoxanthine analog, it is oxidized to alloxanthine, which cannot be further oxidized but acts as a tight binding inhibitor of XDH. The 3.0 A resolution structure of the XDH-alloxanthine complex shows direct coordination of alloxanthine to the molybdenum via a nitrogen atom. These results provide a starting point for the rational design of new XDH inhibitors.

Full Text

Duke Authors

Cited Authors

  • Truglio, JJ; Theis, K; Leimkühler, S; Rappa, R; Rajagopalan, KV; Kisker, C

Published Date

  • January 2002

Published In

Volume / Issue

  • 10 / 1

Start / End Page

  • 115 - 125

PubMed ID

  • 11796116

International Standard Serial Number (ISSN)

  • 0969-2126

Digital Object Identifier (DOI)

  • 10.1016/s0969-2126(01)00697-9


  • eng

Conference Location

  • United States