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2l8r

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2l8r, 20 NMR models ()
Sites:
Ligands:
Gene: C6orf130 (Homo sapiens)
Related: 2jyc, 2lgr


Resources: FirstGlance, OCA, PDBsum, RCSB
Coordinates: save as pdb, mmCIF, xml



Solution structure of human protein C6orf130 in complex with ADP-ribose

Publication Abstract from PubMed

Post-translational modification of proteins/histones by lysine acylation has profound effects on the physiological function of modified proteins. Deacylation by NAD(+)-dependent sirtuin reactions yields as a product O-acyl-ADP-ribose, which has been implicated as a signaling molecule in modulating cellular processes. Macrodomain-containing proteins are reported to bind NAD(+)-derived metabolites. Here, we describe the structure and function of an orphan macrodomain protein, human C6orf130. This unique 17-kDa protein is a stand-alone macrodomain protein that occupies a distinct branch in the phylogenic tree. We demonstrate that C6orf130 catalyzes the efficient deacylation of O-acetyl-ADP-ribose, O-propionyl-ADP-ribose, and O-butyryl-ADP-ribose to produce ADP-ribose (ADPr) and acetate, propionate, and butyrate, respectively. Using NMR spectroscopy, we solved the structure of C6orf130 in the presence and absence of ADPr. The structures showed a canonical fold with a deep ligand (ADPr)-binding cleft. Structural comparisons of apo-C6orf130 and the ADPr-C6orf130 complex revealed fluctuations of the beta(5)-alpha(4) loop that covers the bound ADPr, suggesting that the beta(5)-alpha(4) loop functions as a gate to sequester substrate and offer flexibility to accommodate alternative substrates. The ADPr-C6orf130 complex identified amino acid residues involved in substrate binding and suggested residues that function in catalysis. Site-specific mutagenesis and steady-state kinetic analyses revealed two critical catalytic residues, Ser-35 and Asp-125. We propose a catalytic mechanism for deacylation of O-acyl-ADP-ribose by C6orf130 and discuss the biological implications in the context of reversible protein acylation at lysine residues.

Orphan Macrodomain Protein (Human C6orf130) Is an O-Acyl-ADP-ribose Deacylase: SOLUTION STRUCTURE AND CATALYTIC PROPERTIES., Peterson FC, Chen D, Lytle BL, Rossi MN, Ahel I, Denu JM, Volkman BF, J Biol Chem. 2011 Oct 14;286(41):35955-65. Epub 2011 Aug 17. PMID:21849506

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

About this Structure

2l8r is a 1 chain structure with sequence from Homo sapiens. Full experimental information is available from OCA.

Reference

  • Peterson FC, Chen D, Lytle BL, Rossi MN, Ahel I, Denu JM, Volkman BF. Orphan Macrodomain Protein (Human C6orf130) Is an O-Acyl-ADP-ribose Deacylase: SOLUTION STRUCTURE AND CATALYTIC PROPERTIES. J Biol Chem. 2011 Oct 14;286(41):35955-65. Epub 2011 Aug 17. PMID:21849506 doi:10.1074/jbc.M111.276238

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