7ARW

Structure of human ARH3 E41A bound to alpha-NAD+ and magnesium

Summary for 7ARW

• Entry DOI: 10.2210/pdb7arw/pdb
• Descriptor: ADP-ribose glycohydrolase ARH3, MAGNESIUM ION, alpha-Diphosphopyridine nucleotide, ... (6 entities in total)
• Functional Keywords: adp-ribose glycohydrolase, arh3, human, alpha-nad+, hydrolase
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 2
• Total formula weight: 77879.50

Authors

Rack, J.G.M.,Zorzini, V.,Ahel, I. (deposition date: 2020-10-26, release date: 2021-06-16, Last modification date: 2024-01-31)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (1.31 Å)