O-Acetyl-ADP Ribose Deacetylase 1 (OARD1)

C6orf130, unique 17-kDa protein is a stand-alone macrodomain protein that occupies a distinct branch in the phylogenic tree. C6orf130 catalyzes the efficient deacylation of O-acetyl-ADP-ribose, O-propionyl-ADP-ribose, and O-butyryl-ADP-ribose to produce ADPr and acetate, propionate, and butyrate, respectively. The structures showed a canonical fold with a deep ligand (ADPr) binding cleft. Structural comparisons of apo-C6orf130 and the ADPr-C6orf130 complex reveal fluctuations of the β5-α4 loop that covers the bound ADPr, suggesting that the β5-α4 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.