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'''High Resolution Crystal Structures of Vaccinia Virus dUTPase''' | '''High Resolution Crystal Structures of Vaccinia Virus dUTPase''' | ||
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[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Vaccinia virus]] | [[Category: Vaccinia virus]] | ||
[[Category: | [[Category: DUTP diphosphatase]] | ||
[[Category: Chattopadhyay, D.]] | [[Category: Chattopadhyay, D.]] | ||
[[Category: Schormann, N.]] | [[Category: Schormann, N.]] | ||
[[Category: | [[Category: Dutpase-like]] | ||
[[Category: | [[Category: Fold]] | ||
[[Category: | [[Category: Forms tight trimer through an additional beta-sheet in each subunit]] | ||
[[Category: | [[Category: Jelly-roll]] | ||
[[Category: | [[Category: Subunit beta-sheets are orthogonally packed around the three-fold axis]] | ||
[[Category: | [[Category: Superfamily]] | ||
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Revision as of 11:05, 4 May 2008
High Resolution Crystal Structures of Vaccinia Virus dUTPase
OverviewOverview
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.
About this StructureAbout this Structure
2OKD is a Single protein structure of sequence from Vaccinia virus. Full crystallographic information is available from OCA.
ReferenceReference
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 Page seeded by OCA on Sun May 4 11:05:24 2008