Enzymes
UniProtKB help_outline | 2,520 proteins |
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- Name help_outline α-NAD+ Identifier CHEBI:77017 Charge -1 Formula C21H26N7O14P2 InChIKeyhelp_outline BAWFJGJZGIEFAR-OPDHFMQKSA-M SMILEShelp_outline NC(=O)c1ccc[n+](c1)[C@H]1O[C@H](COP([O-])(=O)OP([O-])(=O)OC[C@H]2O[C@H]([C@H](O)[C@@H]2O)n2cnc3c(N)ncnc23)[C@@H](O)[C@H]1O 2D coordinates Mol file for the small molecule Search links Involved in 1 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
- Name help_outline H2O Identifier CHEBI:15377 (Beilstein: 3587155; CAS: 7732-18-5) help_outline Charge 0 Formula H2O InChIKeyhelp_outline XLYOFNOQVPJJNP-UHFFFAOYSA-N SMILEShelp_outline [H]O[H] 2D coordinates Mol file for the small molecule Search links Involved in 6,204 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
- Name help_outline ADP-D-ribose Identifier CHEBI:57967 Charge -2 Formula C15H21N5O14P2 InChIKeyhelp_outline SRNWOUGRCWSEMX-TYASJMOZSA-L SMILEShelp_outline Nc1ncnc2n(cnc12)[C@@H]1O[C@H](COP([O-])(=O)OP([O-])(=O)OC[C@H]2OC(O)[C@H](O)[C@@H]2O)[C@@H](O)[C@H]1O 2D coordinates Mol file for the small molecule Search links Involved in 22 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
- Name help_outline H+ Identifier CHEBI:15378 Charge 1 Formula H InChIKeyhelp_outline GPRLSGONYQIRFK-UHFFFAOYSA-N SMILEShelp_outline [H+] 2D coordinates Mol file for the small molecule Search links Involved in 9,431 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
- Name help_outline nicotinamide Identifier CHEBI:17154 (Beilstein: 383619; CAS: 98-92-0) help_outline Charge 0 Formula C6H6N2O InChIKeyhelp_outline DFPAKSUCGFBDDF-UHFFFAOYSA-N SMILEShelp_outline NC(=O)c1cccnc1 2D coordinates Mol file for the small molecule Search links Involved in 61 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
Cross-references
RHEA:68792 | RHEA:68793 | RHEA:68794 | RHEA:68795 | |
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Reaction direction help_outline | undefined | left-to-right | right-to-left | bidirectional |
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Publications
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Mechanistic insights into the three steps of poly(ADP-ribosylation) reversal.
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.
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 chrom ... >> More
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. << Less
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The ARH and Macrodomain Families of alpha-ADP-ribose-acceptor Hydrolases Catalyze alpha-NAD+ Hydrolysis.
Stevens L.A., Kato J., Kasamatsu A., Oda H., Lee D.Y., Moss J.
ADP-ribosyltransferases transfer ADP-ribose from β-NAD<sup>+</sup> to acceptors; ADP-ribosylated acceptors are cleaved by ADP-ribosyl-acceptor hydrolases (ARHs) and proteins containing ADP-ribose-binding modules termed macrodomains. On the basis of the ADP-ribosyl-arginine hydrolase 1 (ARH1) stere ... >> More
ADP-ribosyltransferases transfer ADP-ribose from β-NAD<sup>+</sup> to acceptors; ADP-ribosylated acceptors are cleaved by ADP-ribosyl-acceptor hydrolases (ARHs) and proteins containing ADP-ribose-binding modules termed macrodomains. On the basis of the ADP-ribosyl-arginine hydrolase 1 (ARH1) stereospecific hydrolysis of α-ADP-ribosyl-arginine and the hypothesis that α-NAD<sup>+</sup> is generated as a side product of β-NAD<sup>+</sup>/ NADH metabolism, we proposed that α-NAD<sup>+</sup> was a substrate of ARHs and macrodomain proteins. Here, we report that ARH1, ARH3, and macrodomain proteins (i.e., MacroD1, MacroD2, C6orf130 (TARG1), Af1521, hydrolyzed α-NAD<sup>+</sup> but not β-NAD<sup>+</sup>. ARH3 had the highest α-NADase specific activity. The ARH and macrodomain protein families, in stereospecific reactions, cleave ADP-ribose linkages to N- or O- containing functional groups; anomerization of α-to β-forms (e.g., α-ADP-ribosyl-arginine to β-ADP-ribose-(arginine) protein) may explain partial hydrolysis of ADP-ribosylated acceptors with an increase in content of ADP-ribosylated substrates. Af1521 and ARH3 crystal structures with bound ADP-ribose revealed similar ADP-ribose-binding pockets with the catalytic residues of the ARH and macrodomain protein families in the N-terminal helix and loop. Although the biological roles of the ARHs and macrodomain proteins differ, they share enzymatic and structural properties that may regulate metabolites such as α-NAD<sup>+</sup>. << Less