4DK2

Crystal Structure of Open Trypanosoma brucei dUTPase

4DK2 の概要

• エントリーDOI: 10.2210/pdb4dk2/pdb
• 関連するPDBエントリー: 4DK4 4DKB 4DL8 4DLC
• 分子名称: Deoxyuridine triphosphatase (2 entities in total)
• 機能のキーワード: all alpha ntp pyrophosphohydrolase, all alpha ntp pyrophosphatase, dutp and mg2+ binding, hydrolase
• 由来する生物種: Trypanosoma brucei
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 33170.31

構造登録者

Hemsworth, G.R.,Gonzalez-Pacanowska, D.,Wilson, K.S. (登録日: 2012-02-03, 公開日: 2013-08-07, 最終更新日: 2023-09-13)

主引用文献

Hemsworth, G.R.,Gonzalez-Pacanowska, D.,Wilson, K.S.
On the catalytic mechanism of dimeric dUTPases.
Biochem.J., 456:81-88, 2013

PubMed Abstract: The Tritryps Trypanosoma brucei, Trypanosoma cruzi and Leishmania donovani are responsible for great morbidity and mortality in developing countries. Their dimeric dUTPases are members of the all-α NTP pyrophosphohydrolase family and represent promising drug targets due to their essential nature and markedly different structural and biochemical properties compared with the trimeric human enzyme. In the present paper we describe the structure of the T. brucei enzyme in open and closed conformations. Furthermore, we probe the reaction mechanism through the binding of transition state mimics both in solution and in the crystal. 31P-NMR and tryptophan fluorescence quenching in the presence of AlF3 and MgF3- identified which phosphate is subject to nucleophilic attack by a water molecule. The structures in complex with two transition state analogues confirm that the nucleophilic attack occurs on the β-phosphate in contrast with the α-phosphate in the trimeric enzymes. These results establish the structural basis of catalysis of these important housekeeping enzymes and has ramifications for the wider all-α NTP pyrophosphohydrolase family.

PubMed: 24001052
DOI: 10.1042/BJ20130796

実験手法

X-RAY DIFFRACTION (1.47 Å)