3HZA

Crystal structure of dUTPase H145W mutant

3HZA の概要

• エントリーDOI: 10.2210/pdb3hza/pdb
• 分子名称: Deoxyuridine 5'-triphosphate nucleotidohydrolase, MAGNESIUM ION, 2'-DEOXYURIDINE 5'-ALPHA,BETA-IMIDO-TRIPHOSPHATE, ... (6 entities in total)
• 機能のキーワード: jelly roll, domain swapping, hydrolase, nucleotide metabolism
• 由来する生物種: Mycobacterium tuberculosis
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 18838.17

構造登録者

Leveles, I.,Harmat, V.,Pecsi, I.,Toth, J.,Vertessy, B.G. (登録日: 2009-06-23, 公開日: 2009-11-24, 最終更新日: 2023-09-06)

主引用文献

Pecsi, I.,Leveles, I.,Harmat, V.,Vertessy, B.G.,Toth, J.
Aromatic stacking between nucleobase and enzyme promotes phosphate ester hydrolysis in dUTPase.
Nucleic Acids Res., 38:7179-7186, 2010

PubMed Abstract: Aromatic interactions are well-known players in molecular recognition but their catalytic role in biological systems is less documented. Here, we report that a conserved aromatic stacking interaction between dUTPase and its nucleotide substrate largely contributes to the stabilization of the associative type transition state of the nucleotide hydrolysis reaction. The effect of the aromatic stacking on catalysis is peculiar in that uracil, the aromatic moiety influenced by the aromatic interaction is relatively distant from the site of hydrolysis at the alpha-phosphate group. Using crystallographic, kinetics, optical spectroscopy and thermodynamics calculation approaches we delineate a possible mechanism by which rate acceleration is achieved through the remote π-π interaction. The abundance of similarly positioned aromatic interactions in various nucleotide hydrolyzing enzymes (e.g. most families of ATPases) raises the possibility of the reported phenomenon being a general component of the enzymatic catalysis of phosphate ester hydrolysis.

PubMed: 20601405
DOI: 10.1093/nar/gkq584

実験手法

X-RAY DIFFRACTION (1.2 Å)