6HH5

ADP-ribosylserine hydrolase ARH3 of Latimeria chalumnae in complex with ADP-HPM

6HH5 の概要

• エントリーDOI: 10.2210/pdb6hh5/pdb
• 分子名称: ADP-ribosylhydrolase like 2, MAGNESIUM ION, Adenosine Diphosphate (Hydroxymethyl)pyrrolidine monoalcohol, ... (5 entities in total)
• 機能のキーワード: adp-ribosylation, adp-ribose, adprhl2, adp-ribosylhydrolase like 2, hydrolase, adp-hpm
• 由来する生物種: Latimeria chalumnae (West Indian ocean coelacanth)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 77864.50

構造登録者

Ariza, A. (登録日: 2018-08-24, 公開日: 2018-11-28, 最終更新日: 2024-01-17)

主引用文献

Rack, J.G.M.,Ariza, A.,Drown, B.S.,Henfrey, C.,Bartlett, E.,Shirai, T.,Hergenrother, P.J.,Ahel, I.
(ADP-ribosyl)hydrolases: Structural Basis for Differential Substrate Recognition and Inhibition.
Cell Chem Biol, 25:1533-1546.e12, 2018

PubMed Abstract: Protein ADP-ribosylation is a highly dynamic post-translational modification. The rapid turnover is achieved, among others, by ADP-(ribosyl)hydrolases (ARHs), an ancient family of enzymes that reverses this modification. Recently ARHs came into focus due to their role as regulators of cellular stresses and tumor suppressors. Here we present a comprehensive structural analysis of the enzymatically active family members ARH1 and ARH3. These two enzymes have very distinct substrate requirements. Our data show that binding of the adenosine ribose moiety is highly diverged between the two enzymes, whereas the active sites harboring the distal ribose closely resemble each other. Despite this apparent similarity, we elucidate the structural basis for the selective inhibition of ARH3 by the ADP-ribose analogues ADP-HPD and arginine-ADP-ribose. Together, our biochemical and structural work provides important insights into the mode of enzyme-ligand interaction, helps to understand differences in their catalytic behavior, and provides useful tools for targeted drug design.

PubMed: 30472116
DOI: 10.1016/j.chembiol.2018.11.001

実験手法

X-RAY DIFFRACTION (1.95 Å)