2OL0

High Resolution Crystal Structures of Vaccinia Virus dUTPase

2OL0 の概要

• エントリーDOI: 10.2210/pdb2ol0/pdb
• 関連するPDBエントリー: 2OKB 2OKD 2OKE 2OL1
• 分子名称: Deoxyuridine 5'-triphosphate nucleotidohydrolase, CHLORIDE ION, MAGNESIUM ION, ... (6 entities in total)
• 機能のキーワード: fold, jelly-roll, superfamily, dutpase-like, forms tight trimer through an additional beta-sheet in each subunit, subunit beta-sheets are orthogonally packed around the three-fold axis, hydrolase
• 由来する生物種: Vaccinia virus
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 50356.57

構造登録者

Schormann, N.,Chattopadhyay, D. (登録日: 2007-01-18, 公開日: 2007-05-01, 最終更新日: 2023-08-30)

主引用文献

Samal, A.,Schormann, N.,Cook, W.J.,Delucas, L.J.,Chattopadhyay, D.
Structures of vaccinia virus dUTPase and its nucleotide complexes.
Acta Crystallogr.,Sect.D, 63:571-580, 2007

PubMed Abstract: 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.

PubMed: 17452782
DOI: 10.1107/S0907444907007871

実験手法

X-RAY DIFFRACTION (2.1 Å)