1V8T

Crystal Structure analysis of the ADP-ribose pyrophosphatase complexed with ribose-5'-phosphate and Zn

Summary for 1V8T

• Entry DOI: 10.2210/pdb1v8t/pdb
• Related: 1V8I 1V8L 1V8M 1V8N 1V8R 1V8S 1V8U 1V8V 1V8W 1V8Y
• Descriptor: ADP-ribose pyrophosphatase, RIBOSE-5-PHOSPHATE, ZINC ION, ... (4 entities in total)
• Functional Keywords: nudix motif, mutt family, loop-helix-loop, riken structural genomics/proteomics initiative, rsgi, structural genomics, hydrolase
• Biological source: Thermus thermophilus
• Total number of polymer chains: 1
• Total formula weight: 19648.84

Authors

Yoshiba, S.,Ooga, T.,Nakagawa, N.,Shibata, T.,Inoue, Y.,Yokoyama, S.,Kuramitsu, S.,Masui, R.,RIKEN Structural Genomics/Proteomics Initiative (RSGI) (deposition date: 2004-01-14, release date: 2004-10-19, Last modification date: 2023-12-27)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (2.6 Å)