7AQM

ADP-ribosylserine hydrolase ARH3 of Latimeria chalumnae in complex with alpha-1''-O-methyl-ADP-ribose (meADPr)

7AQM の概要

• エントリーDOI: 10.2210/pdb7aqm/pdb
• 分子名称: ADP-ribosylhydrolase like 2, MAGNESIUM ION, Adenosine 5'-diphosphoric acid beta-[(3beta,4beta-dihydroxy-5beta-methoxytetrahydrofuran-2alpha-yl)methyl] estere, ... (4 entities in total)
• 機能のキーワード: adp-ribosylserine hydrolase, arh3, latimeria chalumnae, alpha-1''-o-methyl-adp ribose, hydrolase
• 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: 77822.94

構造登録者

Rack, J.G.M.,Zorzini, V.,Ahel, I. (登録日: 2020-10-22, 公開日: 2021-06-16, 最終更新日: 2024-01-31)

主引用文献

Rack, J.G.M.,Liu, Q.,Zorzini, V.,Voorneveld, J.,Ariza, A.,Honarmand Ebrahimi, K.,Reber, J.M.,Krassnig, S.C.,Ahel, D.,van der Marel, G.A.,Mangerich, A.,McCullagh, J.S.O.,Filippov, D.V.,Ahel, I.
Mechanistic insights into the three steps of poly(ADP-ribosylation) reversal.
Nat Commun, 12:4581-4581, 2021

PubMed Abstract: Poly(ADP-ribosyl)ation (PAR) is a versatile and complex posttranslational modification composed of repeating units of ADP-ribose arranged into linear or branched polymers. This scaffold is linked to the regulation of many of cellular processes including the DNA damage response, alteration of chromatin structure and Wnt signalling. Despite decades of research, the principles and mechanisms underlying all steps of PAR removal remain actively studied. In this work, we synthesise well-defined PAR branch point molecules and demonstrate that PARG, but not ARH3, can resolve this distinct PAR architecture. Structural analysis of ARH3 in complex with dimeric ADP-ribose as well as an ADP-ribosylated peptide reveal the molecular basis for the hydrolysis of linear and terminal ADP-ribose linkages. We find that ARH3-dependent hydrolysis requires both rearrangement of a catalytic glutamate and induction of an unusual, square-pyramidal magnesium coordination geometry.

PubMed: 34321462
DOI: 10.1038/s41467-021-24723-3

実験手法

X-RAY DIFFRACTION (2.5 Å)