ArticleACS chemical biology2014
Transition-state analysis of 2-O-acetyl-ADP-ribose hydrolysis by human macrodomain 1.
Article in ACS chemical biology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
6 citing papers in PubMed.
- PARP14 is a writer, reader, and eraser of mono-ADP-ribosylation.The Journal of biological chemistry · 2023Article
- A molecular toolbox for ADP-ribosyl binding proteins.Cell reports methods · 2021Article
- ADP-ribosylation systems in bacteria and viruses.Computational and structural biotechnology journal · 2021Review
- Article
- Review
- Structural and functional analysis ofOpen biology · 2017Article
Corrections and comments
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Authors and funding
3 authors.
Funding
Abstract
Macrodomains, including the human macrodomain 1 (MacroD1), are erasers of the post-translational modification of monoadenosinediphospho-ribosylation and hydrolytically deacetylate the sirtuin product O-acetyl-ADP-ribose (OAADPr). OAADPr has been reported to play a role in cell signaling based on oocyte microinjection studies, and macrodomains affect an array of cell processes including transcription and response to DNA damage. Here, we investigate human MacroD1 by transition-state (TS) analysis based on kinetic isotope effects (KIEs) from isotopically labeled OAADPr substrates. Competitive radiolabeled-isotope effects and mass spectrometry were used to obtain KIE data to yield intrinsic KIE values. Intrinsic KIEs were matched to a quantum chemical structure of the TS that includes the active site residues Asp184 and Asn174 and a structural water molecule. Transition-state analysis supports a concerted mechanism with an early TS involving simultaneous nucleophilic water attack and leaving group bond cleavage where the breaking C-O ester bond=1.60 Å and the C-O bond to the attacking water nucleophile=2.30 Å. The MacroD1 TS provides mechanistic understanding of the OAADPr esterase chemistry.
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Registered trials
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