1JRP

Crystal Structure of Xanthine Dehydrogenase inhibited by alloxanthine from Rhodobacter capsulatus

Summary for 1JRP

• Entry DOI: 10.2210/pdb1jrp/pdb
• Related: 1JRO
• Descriptor: xanthine dehydrogenase, chain A, xanthine dehydrogenase, chain B, FE2/S2 (INORGANIC) CLUSTER, ... (8 entities in total)
• Functional Keywords: partial beta-barrel; xdh; xo, oxidoreductase
• Biological source: Rhodobacter capsulatus; More
• Total number of polymer chains: 8
• Total formula weight: 536844.91

Authors

Truglio, J.J.,Theis, K.,Leimkuhler, S.,Rappa, R.,Rajagopalan, K.V.,Kisker, C. (deposition date: 2001-08-14, release date: 2002-01-11, Last modification date: 2024-10-30)

Primary citation

Truglio, J.J.,Theis, K.,Leimkuhler, S.,Rappa, R.,Rajagopalan, K.V.,Kisker, C.
Crystal structures of the active and alloxanthine-inhibited forms of xanthine dehydrogenase from Rhodobacter capsulatus
Structure, 10:115-125, 2002

PubMed Abstract: 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.

PubMed: 11796116
DOI: 10.1016/S0969-2126(01)00697-9

Experimental method

X-RAY DIFFRACTION (3 Å)