The 39-kDa poly(ADP-ribose) glycohydrolase ARH3 hydrolyzes
            <i>O-</i>
            acetyl-ADP-ribose, a product of the Sir2 family of acetyl-histone deacetylases

Ono, Tohru; Kasamatsu, Atsushi; Oka, Shunya; Moss, Joel

doi:10.1073/pnas.0607911103

Cited by 99 publications

(125 citation statements)

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“…ARH3 hydrolyzes not only OAADPr, but also poly(ADPr) (10,11). However, ARH3-catalyzed generation of ADPr from OAADPr was significantly faster than that from poly(ADPr) (11).…”

Section: Discussionmentioning

confidence: 90%

“…ADPr was an effective inhibitor, likely due to competition for substrate binding within the ARH3 catalytic active site (11). In contrast to ADPr (11), 2Љ-and 3Љ-N-acetyl-ADPr were poor ARH3 inhibitors.…”

Section: Discussionmentioning

confidence: 99%

“…However, ARH3-catalyzed generation of ADPr from OAADPr was significantly faster than that from poly(ADPr) (11). Poly(ADPr) is a homopolymer of ADPr molecules, linked by ribose-ribose (C-1Љ to C-2Ј) glycosidic bonds in a linear or branched structure (25,26).…”

Section: Discussionmentioning

confidence: 99%

“…OAADPr isomers, 1 M OAADPr in 50 mM potassium phosphate (pH 9.0), 10 mM MgCl 2 , and 5 mM DTT (total volume, 200 l) were incubated (5 min at room temperature), before separation of isomers using RP-HPLC and analysis by MALDI-TOF mass spectrometry as described previously (11). Briefly, before mass spectrometry, 10 mg of ␣-cyano-4-hydroxycinnamic acid (Bruker Daltonics, Billerica, MA) was mixed in 1 ml of water/acetonitrile (50:50, v/v) containing TFA.…”

Section: Identification Of Isomers Of O-acetyl-adp-ribose-for Identifmentioning

confidence: 99%

“…As with the ARH1-catalyzed reaction, ADP-ribose is a potent inhibitor. ARH3 also hydrolyzed O-acetyl-ADP-ribose (OAADPr) in a Mg 2ϩ -dependent manner to produce ADPr, which inhibited these two ARH3-catalyzed reactions (10,11). Both poly(ADPr) and OAADPr participate in important biological pathways.…”

mentioning

confidence: 99%

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Hydrolysis of O-Acetyl-ADP-ribose Isomers by ADP-ribosylhydrolase 3

Kasamatsu

Nakao

Smith

et al. 2011

Journal of Biological Chemistry

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O-Acetyl-ADP-ribose (OAADPr), produced by the Sir2-catalyzed NAD ؉ -dependent histone/protein deacetylase reaction, regulates diverse biological processes. Interconversion between two OAADPr isomers with acetyl attached to the C-2؆ and C-3؆ hydroxyl of ADP-ribose (ADPr) is rapid. We reported earlier that ADP-ribosylhydrolase 3 (ARH3), one of three ARH proteins sharing structural similarities, hydrolyzed OAADPr to ADPr and acetate, and poly(ADPr) to ADPr monomers. ARH1 also hydrolyzed OAADPr and poly(ADPr) as well as ADP-ribose-arginine, with arginine in ␣-anomeric linkage to C-1؆ of ADP-ribose. Because both ARH3-and ARH1-catalyzed reactions involve nucleophilic attacks at the C-1؆ position, it was perplexing that the ARH3 catalytic site would cleave OAADPr at either the 2؆-or 3؆-position, and we postulated the existence of a third isomer, 1؆-OAADPr, in equilibrium with 2؆-and 3؆-isomers. A third isomer, consistent with 1؆-OAADPr, was identified at pH 9.0. Further, ARH3 OAADPr hydrolase activity was greater at pH 9.0 than at neutral pH where 3؆-OAADPr predominated. Consistent with our hypothesis, IC 50 values for ARH3 inhibition by 2؆-and 3؆-N-acetyl-ADPr analogs of OAADPr were significantly higher than that for ADPr. ARH1 also hydrolyzed OAADPr more rapidly at alkaline pH, but cleavage of ADP-ribose-arginine was faster at neutral pH than pH 9.0. ARH3-catalyzed hydrolysis of OAADPr in H 218 O resulted in incorporation of one 18 O into ADP-ribose by mass spectrometric analysis, consistent with cleavage at the C-1؆ position. Together, these data suggest that ARH family members, ARH1 and ARH3, catalyze hydrolysis of the 1؆-O linkage in their structurally diverse substrates.Mono-ADP-ribosylation is a post-translational modification, in which the ADP-ribose (ADPr) 5 moiety of NAD is transferred to an acceptor protein (1). This modification serves as the mechanism by which several bacterial toxins (e.g. Pseudomonas exoenzyme S, cholera toxin, diphtheria toxin) exert their effects on mammalian cells (2, 3). Mammalian cells also produce endogenous ADP-ribosyltransferases that catalyze reactions similar to the bacterial toxins, specifically, the ADPribosylation of arginine residues in proteins (4). In addition, mammalian cells possess hydrolases that cleave the ADPr-protein linkage, releasing ADPr and regenerating the unmodified protein (5, 6). An ADP-ribosyl(arginine) hydrolase, termed ARH1, catalyzes in a stereospecific manner, hydrolysis of the ␣-linkage of arginine-ribose found in ADP-ribosyl(arginine)-protein to ADPr and (arginine)-protein (7, 8), consistent with the regulation of ADP-ribosyl(arginine)-protein levels by opposing activities of transferases and hydrolases, participating in an ADP-ribosylation cycle (4, 9).Three known members (ARH1-3) of the ARH family of proteins are similar in molecular size (ϳ39 kDa) and amino acid sequence (10). As noted above, ARH1 catalyzes the hydrolysis of ADP-ribose-arginine and also hydrolyzes ADP-ribose linkages to guanidine. The reaction is stereospecific, and only the ␣-ano...

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“…ARH3 hydrolyzes not only OAADPr, but also poly(ADPr) (10,11). However, ARH3-catalyzed generation of ADPr from OAADPr was significantly faster than that from poly(ADPr) (11).…”

Section: Discussionmentioning

confidence: 90%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Identification Of Isomers Of O-acetyl-adp-ribose-for Identifmentioning

confidence: 99%

mentioning

confidence: 99%

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Hydrolysis of O-Acetyl-ADP-ribose Isomers by ADP-ribosylhydrolase 3

Kasamatsu

Nakao

Smith

et al. 2011

Journal of Biological Chemistry

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Solid‐Phase Synthesis and Biological Evaluation of Peptides ADP‐Ribosylated at Histidine

Minnee,

Rack,

van der Marel

et al. 2023

Angewandte Chemie

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The transfer of an adenosine diphosphate (ADP) ribose moiety to a nucleophilic side chain by consumption of nicotinamide adenine dinucleotide is referred to as ADP‐ribosylation, which allows for the spatiotemporal regulation of vital processes such as apoptosis and DNA repair. Recent mass‐spectrometry based analyses of the “ADP‐ribosylome” have identified histidine as ADP‐ribose acceptor site. In order to study this modification, a fully synthetic strategy towards α‐configured N(τ)‐ and N(π)‐ADP‐ribosylated histidine‐containing peptides has been developed. Ribofuranosylated histidine building blocks were obtained via Mukaiyama‐type glycosylation and the building blocks were integrated into an ADP‐ribosylome derived peptide sequence using fluorenylmethyloxycarbonyl (Fmoc)‐based solid‐phase peptide synthesis. On‐resin installation of the ADP moiety was achieved using phosphoramidite chemistry, and global deprotection provided the desired ADP‐ribosylated oligopeptides. The stability under various chemical conditions and resistance against (ADP‐ribosyl) hydrolase‐mediated degradation has been investigated to reveal that the constructs are stable under various chemical conditions and non‐degradable by any of the known ADP‐ribosylhydrolases.

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