Publication Date:
2011-11-15
Description:
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.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3217313/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3217313/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Du, Jintang -- Zhou, Yeyun -- Su, Xiaoyang -- Yu, Jiu Jiu -- Khan, Saba -- Jiang, Hong -- Kim, Jungwoo -- Woo, Jimin -- Kim, Jun Huyn -- Choi, Brian Hyun -- He, Bin -- Chen, Wei -- Zhang, Sheng -- Cerione, Richard A -- Auwerx, Johan -- Hao, Quan -- Lin, Hening -- 231138/European Research Council/International -- DK58920/DK/NIDDK NIH HHS/ -- P41 RR001646/RR/NCRR NIH HHS/ -- P41 RR001646-27/RR/NCRR NIH HHS/ -- R01 GM086703/GM/NIGMS NIH HHS/ -- R01 GM086703-03/GM/NIGMS NIH HHS/ -- R01 GM086703-03S1/GM/NIGMS NIH HHS/ -- R01GM086703/GM/NIGMS NIH HHS/ -- RR01646/RR/NCRR NIH HHS/ -- New York, N.Y. -- Science. 2011 Nov 11;334(6057):806-9. doi: 10.1126/science.1207861.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Chemistry and Chemical Biology, Cornell University, Ithaca, NY 14853, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22076378" target="_blank"〉PubMed〈/a〉
Keywords:
Acetylation
;
Animals
;
Carbamoyl-Phosphate Synthase (Ammonia)/metabolism
;
Cattle
;
Crystallography, X-Ray
;
Histones/metabolism
;
Humans
;
Hydrogen Bonding
;
Hydrophobic and Hydrophilic Interactions
;
Kinetics
;
Lysine/*metabolism
;
Male
;
Mice
;
Mice, Knockout
;
Mitochondria, Liver/metabolism
;
NAD/metabolism
;
Peptides/*metabolism
;
Protein Processing, Post-Translational
;
Sirtuins/chemistry/genetics/*metabolism
;
Succinic Acid/*metabolism
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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