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

Publication ,  Journal Article
Truglio, JJ; Theis, K; Leimkühler, S; Rappa, R; Rajagopalan, KV; Kisker, C
Published in: Structure
January 2002

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.

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Published In

Structure

DOI

ISSN

0969-2126

Publication Date

January 2002

Volume

10

Issue

1

Start / End Page

115 / 125

Location

United States

Related Subject Headings

  • Xanthine Dehydrogenase
  • Sequence Alignment
  • Rhodobacter capsulatus
  • Protein Structure, Quaternary
  • Oxypurinol
  • Molecular Structure
  • Molecular Sequence Data
  • Models, Molecular
  • Humans
  • Enzyme Inhibitors
 

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Truglio, J. J., Theis, K., Leimkühler, S., Rappa, R., Rajagopalan, K. V., & Kisker, C. (2002). Crystal structures of the active and alloxanthine-inhibited forms of xanthine dehydrogenase from Rhodobacter capsulatus. Structure, 10(1), 115–125. https://doi.org/10.1016/s0969-2126(01)00697-9
Truglio, James J., Karsten Theis, Silke Leimkühler, Roberto Rappa, K. V. Rajagopalan, and Caroline Kisker. “Crystal structures of the active and alloxanthine-inhibited forms of xanthine dehydrogenase from Rhodobacter capsulatus.Structure 10, no. 1 (January 2002): 115–25. https://doi.org/10.1016/s0969-2126(01)00697-9.
Truglio JJ, Theis K, Leimkühler S, Rappa R, Rajagopalan KV, Kisker C. Crystal structures of the active and alloxanthine-inhibited forms of xanthine dehydrogenase from Rhodobacter capsulatus. Structure. 2002 Jan;10(1):115–25.
Truglio, James J., et al. “Crystal structures of the active and alloxanthine-inhibited forms of xanthine dehydrogenase from Rhodobacter capsulatus.Structure, vol. 10, no. 1, Jan. 2002, pp. 115–25. Pubmed, doi:10.1016/s0969-2126(01)00697-9.
Truglio JJ, Theis K, Leimkühler S, Rappa R, Rajagopalan KV, Kisker C. Crystal structures of the active and alloxanthine-inhibited forms of xanthine dehydrogenase from Rhodobacter capsulatus. Structure. 2002 Jan;10(1):115–125.
Journal cover image

Published In

Structure

DOI

ISSN

0969-2126

Publication Date

January 2002

Volume

10

Issue

1

Start / End Page

115 / 125

Location

United States

Related Subject Headings

  • Xanthine Dehydrogenase
  • Sequence Alignment
  • Rhodobacter capsulatus
  • Protein Structure, Quaternary
  • Oxypurinol
  • Molecular Structure
  • Molecular Sequence Data
  • Models, Molecular
  • Humans
  • Enzyme Inhibitors