title: Sirt5 is a NAD-dependent protein lysine demalonylase and desuccinylase.
abstract: Silent information regulator 2 (Sir2) proteins (sirtuins) are nicotinamide adenine dinucleotide-dependent deacetylases that regulate important biological processes. Mammals have seven sirtuins, Sirt1 to Sirt7. Four of them (Sirt4 to Sirt7) have no detectable or very weak deacetylase activity. We found that Sirt5 is an efficient protein lysine desuccinylase and demalonylase in vitro. The preference for succinyl and malonyl groups was explained by the presence of an arginine residue (Arg(105)) and tyrosine residue (Tyr(102)) in the acyl pocket of Sirt5. Several mammalian proteins were identified with mass spectrometry to have succinyl or malonyl lysine modifications. Deletion of Sirt5 in mice appeared to increase the level of succinylation on carbamoyl phosphate synthase 1, which is a known target of Sirt5. Thus, protein lysine succinylation may represent a posttranslational modification that can be reversed by Sirt5 in vivo.
authors.affiliation: Department of Chemistry and Chemical Biology, Cornell University, Ithaca, NY 14853, USA.
authors.forename: Jintang
authors.initials: J
authors.lastname: Du
authors.forename: Yeyun
authors.initials: Y
authors.lastname: Zhou
authors.forename: Xiaoyang
authors.initials: X
authors.lastname: Su
authors.forename: Jiu Jiu
authors.initials: JJ
authors.lastname: Yu
authors.forename: Saba
authors.initials: S
authors.lastname: Khan
authors.forename: Hong
authors.initials: H
authors.lastname: Jiang
authors.forename: Jungwoo
authors.initials: J
authors.lastname: Kim
authors.forename: Jimin
authors.initials: J
authors.lastname: Woo
authors.forename: Jun Huyn
authors.initials: JH
authors.lastname: Kim
authors.forename: Brian Hyun
authors.initials: BH
authors.lastname: Choi
authors.forename: Bin
authors.initials: B
authors.lastname: He
authors.forename: Wei
authors.initials: W
authors.lastname: Chen
authors.forename: Sheng
authors.initials: S
authors.lastname: Zhang
authors.forename: Richard A
authors.initials: RA
authors.lastname: Cerione
authors.forename: Johan
authors.initials: J
authors.lastname: Auwerx
authors.forename: Quan
authors.initials: Q
authors.lastname: Hao
authors.forename: Hening
authors.initials: H
authors.lastname: Lin
mesh_terms: D000107:Acetylation; D000818:Animals; D002222:Carbamoyl-Phosphate Synthase (Ammonia) / Q000378:metabolism; D002417:Cattle; D018360:Crystallography, X-Ray; D006657:Histones / Q000378:metabolism; D006801:Humans; D006860:Hydrogen Bonding; D057927:Hydrophobic and Hydrophilic Interactions; D007700:Kinetics; D008239:Lysine / Q000378:metabolism*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008930:Mitochondria, Liver / Q000378:metabolism; D009243:NAD / Q000378:metabolism; D010455:Peptides / Q000378:metabolism*; D011499:Protein Processing, Post-Translational; D037761:Sirtuins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D019802:Succinic Acid / Q000378:metabolism*
chemical_list: D006657:Histones; D010455:Peptides; C542554:SIRT5 protein, mouse; D009243:NAD; D019802:Succinic Acid; C508544:SIRT5 protein, human; D037761:Sirtuins; D002222:Carbamoyl-Phosphate Synthase (Ammonia); D008239:Lysine
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