title: Integrative chemical biology approaches for identification and characterization of "erasers" for fatty-acid-acylated lysine residues within proteins.
abstract: Acylation of proteins with fatty acids is important for the regulation of membrane association, trafficking, subcellular localization, and activity of many cellular proteins. While significant progress has been made in our understanding of the two major forms of protein acylation with fatty acids, N-myristoylation and S-palmitoylation, studies of the acylation of lysine residues, within proteins, with fatty acids have lagged behind. Demonstrated here is the use of integrative chemical biology approaches to examine human sirtuins as de-fatty-acid acylases in vitro and in cells. Photo-crosslinking chemistry is used to investigate enzymes which recognize fatty-acid acylated lysine. Human Sirt2 was identified as a robust lysine de-fatty-acid acylase in vitro. The results also show that Sirt2 can regulate the acylation of lysine residues, of proteins, with fatty acids within cells.
authors.affiliation: Department of Chemistry, The University of Hong Kong, Pokfulam Road, Hong Kong (China).
authors.forename: Zheng
authors.initials: Z
authors.lastname: Liu
authors.forename: Tangpo
authors.initials: T
authors.lastname: Yang
authors.forename: Xin
authors.initials: X
authors.lastname: Li
authors.forename: Tao
authors.initials: T
authors.lastname: Peng
authors.forename: Howard C
authors.initials: HC
authors.lastname: Hang
authors.forename: Xiang David
authors.initials: XD
authors.lastname: Li
mesh_terms: D000215:Acylation; D000581:Amidohydrolases / Q000378:metabolism; D000595:Amino Acid Sequence; D002851:Chromatography, High Pressure Liquid; D004591:Electrophoresis, Polyacrylamide Gel; D006367:HeLa Cells; D006657:Histones / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D055666:Lipopeptides / Q000032:analysis; D054878:Lipoylation; D008239:Lysine / Q000378:metabolism*; D013058:Mass Spectrometry; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D056565:Sirtuin 2 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*
chemical_list: D006657:Histones; D055666:Lipopeptides; D034741:RNA, Small Interfering; D000581:Amidohydrolases; D056565:Sirtuin 2; D008239:Lysine
keywords: click chemistry; fatty acids; peptides; photochemistry; protein modifications