3RIG

Sirt5 is an NAD-dependent protein lysine demalonylase and desuccinylase

Summary for 3RIG

• Entry DOI: 10.2210/pdb3rig/pdb
• Related: 3RIY
• Descriptor: NAD-dependent deacetylase sirtuin-5, peptide of histone 3 thioacetyl-lysine 9, ZINC ION, ... (5 entities in total)
• Functional Keywords: protein lysine demalonylase/desuccinylase, zn-binding domain, rossmann fold, mitochondria, hydrolase
• Biological source: Homo sapiens (human); More
• Cellular location: Mitochondrion matrix. Isoform 1: Cytoplasm . Isoform 2: Mitochondrion : Q9NXA8
• Total number of polymer chains: 4
• Total formula weight: 62482.02

Authors

Zhou, Y. (deposition date: 2011-04-13, release date: 2011-11-23, Last modification date: 2023-11-01)

Primary citation

Du, J.,Zhou, Y.,Su, X.,Yu, J.J.,Khan, S.,Jiang, H.,Kim, J.,Woo, J.,Kim, J.H.,Choi, B.H.,He, B.,Chen, W.,Zhang, S.,Cerione, R.A.,Auwerx, J.,Hao, Q.,Lin, H.
Sirt5 is a NAD-dependent protein lysine demalonylase and desuccinylase
Science, 334:806-809, 2011

PubMed 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.

PubMed: 22076378
DOI: 10.1126/science.1207861

Experimental method

X-RAY DIFFRACTION (2 Å)