Inhibitors to understand molecular mechanisms of NAD(+)-dependent deacetylases (sirtuins).
Histone deacetylases (HDACs) are enzymes that cleave acetyl groups from acetyl-lysine residues in histones and various nonhistone proteins. Unlike the other three of the four classes of HDACs that have been identified in humans, which are zinc-dependent amidohydrolases, class III HDACs depend on nicotinamide adenine dinucleotide (NAD(+)) for their catalytic activity. The seven members of the class III HDACs are also named sirtuins for their homology to Sir2p, a yeast histone deacetylase. Sirtuin inhibitors have been critical for the linkage of sirtuin activity to many physiological and pathological processes, and sirtuin activity has been associated with the pathogenesis of cancer, HIV, and metabolic and neurological diseases. Presented here is an overview of the many sirtuin inhibitors that have provided insight into the biological role of sirtuins.
Lawson
Michael
M
Department of Pharmaceutical Chemistry, Martin-Luther Universität Halle-Wittenberg, Wolfgang-Langenbeckstr. 4, 06120 Halle/Saale, Germany.
Uciechowska
Urszula
U
Schemies
Jörg
J
Rumpf
Tobias
T
Jung
Manfred
M
Sippl
Wolfgang
W
D000818:Animals; D015658:HIV Infections / Q000188:drug therapy / Q000201:enzymology; D056572:Histone Deacetylase Inhibitors / Q000737:chemistry / Q000378:metabolism / Q000627:therapeutic use; D006801:Humans; D008659:Metabolic Diseases / Q000188:drug therapy / Q000201:enzymology; D009243:NAD / Q000737:chemistry / Q000378:metabolism; D009369:Neoplasms / Q000188:drug therapy / Q000201:enzymology; D009422:Nervous System Diseases / Q000188:drug therapy / Q000201:enzymology; D037761:Sirtuins / Q000737:chemistry / Q000378:metabolism
D056572:Histone Deacetylase Inhibitors; D009243:NAD; D037761:Sirtuins