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Publication Abstract from PubMed

Deoxyuridine triphosphate nucleotidohydrolase (dUTPase) catalyzes the hydrolysis of dUTP to dUMP and pyrophosphate in the presence of Mg(2+) ions. The enzyme plays multiple cellular roles by maintaining a low dUTP:dTTP ratio and by synthesizing the substrate for thymidylate synthase in the biosynthesis of dTTP. Although dUTPase is an essential enzyme and has been established as a valid target for drug design, the high degree of homology of vaccinia virus dUTPase to the human enzyme makes the identification of selective inhibitors difficult. The crystal structure of vaccinia virus dUTPase has been solved and the active site has been mapped by crystallographic analysis of the apo enzyme and of complexes with the substrate-analog dUMPNPP, with the product dUMP and with dUDP, which acts as an inhibitor. Analyses of these structures reveal subtle differences between the viral and human enzymes. In particular, the much larger size of the central channel at the trimer interface suggests new possibilities for structure-based drug design. Vaccinia virus is a prototype of the poxviruses.

Structures of vaccinia virus dUTPase and its nucleotide complexes.,Samal A, Schormann N, Cook WJ, DeLucas LJ, Chattopadhyay D Acta Crystallogr D Biol Crystallogr. 2007 May;63(Pt 5):571-80. Epub 2007, Apr 21. PMID:17452782^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.