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Article: Sirt5 is a NAD-dependent protein lysine demalonylase and desuccinylase
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TitleSirt5 is a NAD-dependent protein lysine demalonylase and desuccinylase
 
AuthorsDu, J1
Zhou, Y1
Su, X1
Yu, JJ3
Khan, S1
Jiang, H1
Kim, J1
Woo, J1
Kim, JH1
Choi, BH1
He, B1
Chen, W1
Zhang, S1
Cerione, RA1
Auwerx, J3
Hao, Q1 2
Lin, H1
 
KeywordsNicotinamide adenine dinucleotide
Phosphorus 32
Sirtuin
Enzyme activity
Mass spectrometry
 
Issue Date2011
 
PublisherAmerican Association for the Advancement of Science. The Journal's web site is located at http://sciencemag.org
 
CitationScience, 2011, v. 334 n. 6057, p. 806-809 [How to Cite?]
DOI: http://dx.doi.org/10.1126/science.1207861
 
AbstractSilent 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.
 
ISSN0036-8075
2013 Impact Factor: 31.477
2013 SCImago Journal Rankings: 12.465
 
DOIhttp://dx.doi.org/10.1126/science.1207861
 
PubMed Central IDPMC3217313
 
ISI Accession Number IDWOS:000296849600047
Funding AgencyGrant Number
Dreyfus Foundation
NIHR01GM086703
RR01646
Hong KongGRF766510
NIH PPGDK58920
European UnionERC-2008-AdG-23118
Ecole Polytechnique Federale de Lausanne
Funding Information:

This work is supported in part by Dreyfus Foundation (H.L.); grants NIH R01GM086703 (H.L.), Hong Kong GRF766510 (Q.H.), NIH RR01646 (R.A.C. and Q.H.), and NIH PPG DK58920 (J.A.); the European Union Ideas program (sirtuins; ERC-2008-AdG-23118 to J.A.); and the Ecole Polytechnique Federale de Lausanne (J.A.). Atomic coordinates and structure factors were deposited in the Protein Data Bank (accession codes 3RIG and 3RIY).

 
ReferencesReferences in Scopus
 
DC FieldValue
dc.contributor.authorDu, J
 
dc.contributor.authorZhou, Y
 
dc.contributor.authorSu, X
 
dc.contributor.authorYu, JJ
 
dc.contributor.authorKhan, S
 
dc.contributor.authorJiang, H
 
dc.contributor.authorKim, J
 
dc.contributor.authorWoo, J
 
dc.contributor.authorKim, JH
 
dc.contributor.authorChoi, BH
 
dc.contributor.authorHe, B
 
dc.contributor.authorChen, W
 
dc.contributor.authorZhang, S
 
dc.contributor.authorCerione, RA
 
dc.contributor.authorAuwerx, J
 
dc.contributor.authorHao, Q
 
dc.contributor.authorLin, H
 
dc.date.accessioned2012-02-28T01:55:54Z
 
dc.date.available2012-02-28T01:55:54Z
 
dc.date.issued2011
 
dc.description.abstractSilent 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.
 
dc.description.naturepostprint
 
dc.identifier.citationScience, 2011, v. 334 n. 6057, p. 806-809 [How to Cite?]
DOI: http://dx.doi.org/10.1126/science.1207861
 
dc.identifier.citeulike10016982
 
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dc.identifier.hkuros198782
 
dc.identifier.isiWOS:000296849600047
Funding AgencyGrant Number
Dreyfus Foundation
NIHR01GM086703
RR01646
Hong KongGRF766510
NIH PPGDK58920
European UnionERC-2008-AdG-23118
Ecole Polytechnique Federale de Lausanne
Funding Information:

This work is supported in part by Dreyfus Foundation (H.L.); grants NIH R01GM086703 (H.L.), Hong Kong GRF766510 (Q.H.), NIH RR01646 (R.A.C. and Q.H.), and NIH PPG DK58920 (J.A.); the European Union Ideas program (sirtuins; ERC-2008-AdG-23118 to J.A.); and the Ecole Polytechnique Federale de Lausanne (J.A.). Atomic coordinates and structure factors were deposited in the Protein Data Bank (accession codes 3RIG and 3RIY).

 
dc.identifier.issn0036-8075
2013 Impact Factor: 31.477
2013 SCImago Journal Rankings: 12.465
 
dc.identifier.issue6057
 
dc.identifier.pmcidPMC3217313
 
dc.identifier.pmid22076378
 
dc.identifier.scopuseid_2-s2.0-81055122671
 
dc.identifier.spage806
 
dc.identifier.urihttp://hdl.handle.net/10722/145585
 
dc.identifier.volume334
 
dc.languageeng
 
dc.publisherAmerican Association for the Advancement of Science. The Journal's web site is located at http://sciencemag.org
 
dc.publisher.placeUnited States
 
dc.relation.ispartofScience
 
dc.relation.referencesReferences in Scopus
 
dc.rightsScience. Copyright © American Association for the Advancement of Science.
 
dc.rightsCreative Commons: Attribution 3.0 Hong Kong License
 
dc.subjectNicotinamide adenine dinucleotide
 
dc.subjectPhosphorus 32
 
dc.subjectSirtuin
 
dc.subjectEnzyme activity
 
dc.subjectMass spectrometry
 
dc.titleSirt5 is a NAD-dependent protein lysine demalonylase and desuccinylase
 
dc.typeArticle
 
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Author Affiliations
  1. Cornell University
  2. The University of Hong Kong
  3. Ecole Polytechnique Federale de Lausanne