1V8V

Crystal structure analysis of the ADP-ribose pyrophosphatase of E86Q mutant, complexed with ADP-ribose and Mg

1V8V の概要

• エントリーDOI: 10.2210/pdb1v8v/pdb
• 関連するPDBエントリー: 1V8I 1V8L 1V8M 1V8N 1V8R 1V8S 1V8T 1V8U 1V8W 1V8Y
• 分子名称: ADP-ribose pyrophosphatase, MAGNESIUM ION, ADENOSINE-5-DIPHOSPHORIBOSE, ... (4 entities in total)
• 機能のキーワード: mutt family, nudix motif, loop-helix-loop, riken structural genomics/proteomics initiative, rsgi, structural genomics, hydrolase
• 由来する生物種: Thermus thermophilus
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 19870.55

構造登録者

Yoshiba, S.,Ooga, T.,Nakagawa, N.,Shibata, T.,Inoue, Y.,Yokoyama, S.,Kuramitsu, S.,Masui, R.,RIKEN Structural Genomics/Proteomics Initiative (RSGI) (登録日: 2004-01-15, 公開日: 2004-10-19, 最終更新日: 2023-12-27)

主引用文献

Yoshiba, S.,Ooga, T.,Nakagawa, N.,Shibata, T.,Inoue, Y.,Yokoyama, S.,Kuramitsu, S.,Masui, R.
Structural insights into the Thermus thermophilus ADP-ribose pyrophosphatase mechanism via crystal structures with the bound substrate and metal
J.Biol.Chem., 279:37163-37174, 2004

PubMed Abstract: ADP-ribose pyrophosphatase (ADPRase) catalyzes the divalent metal ion-dependent hydrolysis of ADP-ribose to ribose 5'-phosphate and AMP. This enzyme plays a key role in regulating the intracellular ADP-ribose levels, and prevents nonenzymatic ADP-ribosylation. To elucidate the pyrophosphatase hydrolysis mechanism employed by this enzyme, structural changes occurring on binding of substrate, metal and product were investigated using crystal structures of ADPRase from an extreme thermophile, Thermus thermophilus HB8. Seven structures were determined, including that of the free enzyme, the Zn(2+)-bound enzyme, the binary complex with ADP-ribose, the ternary complexes with ADP-ribose and Zn(2+) or Gd(3+), and the product complexes with AMP and Mg(2+) or with ribose 5'-phosphate and Zn(2+). The structural and functional studies suggested that the ADP-ribose hydrolysis pathway consists of four reaction states: bound with metal (I), metal and substrate (II), metal and substrate in the transition state (III), and products (IV). In reaction state II, Glu-82 and Glu-70 abstract a proton from a water molecule. This water molecule is situated at an ideal position to carry out nucleophilic attack on the adenosyl phosphate, as it is 3.6 A away from the target phosphorus and almost in line with the scissile bond.

PubMed: 15210687
DOI: 10.1074/jbc.M403817200

実験手法

X-RAY DIFFRACTION (1.97 Å)