4IQY

Crystal structure of the human protein-proximal ADP-ribosyl-hydrolase MacroD2

Summary for 4IQY

• Entry DOI: 10.2210/pdb4iqy/pdb
• Descriptor: O-acetyl-ADP-ribose deacetylase MACROD2, [(2R,3S,4R,5R)-5-(6-AMINOPURIN-9-YL)-3,4-DIHYDROXY-OXOLAN-2-YL]METHYL [HYDROXY-[[(2R,3S,4R,5S)-3,4,5-TRIHYDROXYOXOLAN-2-YL]METHOXY]PHOSPHORYL] HYDROGEN PHOSPHATE, MAGNESIUM ION, ... (4 entities in total)
• Functional Keywords: macrodomain, hydrolase, adp-ribose binding, adp-ribosylation, nuclear/cytoplasmic
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 2
• Total formula weight: 55307.62

Authors

Jankevicius, G.,Hassler, M.,Golia, B.,Rybin, V.,Zacharias, M.,Timinszky, G.,Ladurner, A.G. (deposition date: 2013-01-14, release date: 2013-03-06, Last modification date: 2023-09-20)

Primary citation

Jankevicius, G.,Hassler, M.,Golia, B.,Rybin, V.,Zacharias, M.,Timinszky, G.,Ladurner, A.G.
A family of macrodomain proteins reverses cellular mono-ADP-ribosylation.
Nat.Struct.Mol.Biol., 20:508-514, 2013

PubMed Abstract: ADP-ribosylation is a reversible post-translational modification with wide-ranging biological functions in all kingdoms of life. A variety of enzymes use NAD(+) to transfer either single or multiple ADP-ribose (ADPr) moieties onto distinct amino acid substrates, often in response to DNA damage or other stresses. Poly-ADPr-glycohydrolase readily reverses poly-ADP-ribosylation induced by the DNA-damage sensor PARP1 and other enzymes, but it does not remove the most proximal ADPr linked to the target amino acid. Searches for enzymes capable of fully reversing cellular mono-ADP-ribosylation back to the unmodified state have proved elusive, which leaves a gap in the understanding of this modification. Here, we identify a family of macrodomain enzymes present in viruses, yeast and animals that reverse cellular ADP-ribosylation by acting on mono-ADP-ribosylated substrates. Our discoveries establish the complete reversibility of PARP-catalyzed cellular ADP-ribosylation as a regulatory modification.

PubMed: 23474712
DOI: 10.1038/nsmb.2523

Experimental method

X-RAY DIFFRACTION (1.55 Å)