5G4C

Human SIRT2 catalyse short chain fatty acyl lysine

Summary for 5G4C

• Entry DOI: 10.2210/pdb5g4c/pdb
• Descriptor: NAD-DEPENDENT PROTEIN DEACETYLASE SIRTUIN-2, SIRT2, ZINC ION, ... (5 entities in total)
• Functional Keywords: hydrolase, sirtuin class i, hdacs, nad dependent, adpr, acyl
• Biological source: HOMO SAPIENS (HUMAN); More
• Total number of polymer chains: 4
• Total formula weight: 75856.10

Authors

Wang, Y. (deposition date: 2016-05-09, release date: 2017-05-03, Last modification date: 2024-01-10)

Primary citation

Jin, J.,He, B.,Zhang, X.,Lin, H.,Wang, Y.
SIRT2 Reverses 4-Oxononanoyl Lysine Modification on Histones.
J. Am. Chem. Soc., 138:12304-12307, 2016

PubMed Abstract: Post-translational modifications (PTMs) regulate numerous proteins and are important for many biological processes. Lysine 4-oxononanoylation (4-ONylation) is a newly discovered histone PTM that prevents nucleosome assembly under oxidative stress. Whether there are cellular enzymes that remove 4-ONyl from histones remains unknown, which hampers the further investigation of the cellular function of this PTM. Here, we report that mammalian SIRT2 can remove 4-ONyl from histones and other proteins in live cells. A crystal structure of SIRT2 in complex with a 4-ONyl peptide reveals a lone pair-π interaction between Phe119 and the ketone oxygen of the 4-ONyl group. This is the first time that a mechanism to reverse 4-ONyl lysine modification is reported and will help to understand the role of SIRT2 in oxidative stress responses and the function of 4-ONylation.

PubMed: 27610633
DOI: 10.1021/jacs.6b04977

Experimental method

X-RAY DIFFRACTION (2.1 Å)