title: The Substrate Specificity of Sirtuins.
abstract: Sirtuins are NAD(+)-dependent enzymes universally present in all organisms, where they play central roles in regulating numerous biological processes. Although early studies showed that sirtuins deacetylated lysines in a reaction that consumes NAD(+), more recent studies have revealed that these enzymes can remove a variety of acyl-lysine modifications. The specificities for varied acyl modifications may thus underlie the distinct roles of the different sirtuins within a given organism. This review summarizes the structure, chemistry, and substrate specificity of sirtuins with a focus on how different sirtuins recognize distinct substrates and thus carry out specific functions.
authors.affiliation: Institut de Génétique et de Biologie Moléculaire et Cellulaire, Illkirch 67404, France.|Institute of Functional Epigenetics, Helmholtz Zentrum München, Neuherberg 85764, Germany.
authors.forename: Poonam
authors.initials: P
authors.lastname: Bheda
authors.affiliation: Department of Chemistry and Chemical Biology, Cornell University, Ithaca, New York 14850.
authors.forename: Hui
authors.initials: H
authors.lastname: Jing
authors.affiliation: Department of Biophysics and Biophysical Chemistry, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205-2185; email: cwolberg@jhmi.edu.
authors.forename: Cynthia
authors.initials: C
authors.lastname: Wolberger
authors.affiliation: Department of Chemistry and Chemical Biology, Cornell University, Ithaca, New York 14850.|Howard Hughes Medical Institute, Cornell University, Ithaca, New York 14850; email: hl379@cornell.edu.
authors.forename: Hening
authors.initials: H
authors.lastname: Lin
mesh_terms: D000215:Acylation; D015870:Gene Expression; D006657:Histones / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D006801:Humans; D006868:Hydrolysis; D007700:Kinetics; D054878:Lipoylation; D008958:Models, Molecular; D019814:Myristic Acid / Q000737:chemistry / Q000378:metabolism; D009243:NAD / Q000737:chemistry* / Q000378:metabolism; D010963:Plasmodium falciparum / Q000737:chemistry / Q000201:enzymology; D011499:Protein Processing, Post-Translational; D017433:Protein Structure, Secondary; D037761:Sirtuins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D013379:Substrate Specificity; D019802:Succinic Acid / Q000737:chemistry / Q000378:metabolism; D020124:Thermotoga maritima / Q000737:chemistry / Q000201:enzymology
chemical_list: D006657:Histones; D019814:Myristic Acid; D009243:NAD; D019802:Succinic Acid; D037761:Sirtuins
keywords: ADP-ribosylation; deacylation; myristoylation; palmitoylation; succinylation