1jrp
Crystal Structure of Xanthine Dehydrogenase inhibited by alloxanthine from Rhodobacter capsulatus
OverviewOverview
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.
About this StructureAbout this Structure
1JRP is a Protein complex structure of sequences from Rhodobacter capsulatus. Full crystallographic information is available from OCA.
ReferenceReference
Crystal structures of the active and alloxanthine-inhibited forms of xanthine dehydrogenase from Rhodobacter capsulatus., Truglio JJ, Theis K, Leimkuhler S, Rappa R, Rajagopalan KV, Kisker C, Structure. 2002 Jan;10(1):115-25. PMID:11796116 Page seeded by OCA on Fri May 2 21:46:24 2008