ArticleCell chemical biology2017
Deacylation Mechanism by SIRT2 Revealed in the 1'-SH-2'-O-Myristoyl Intermediate Structure.
Article in Cell chemical biology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed.
- SIRT1 in Neurodegenerative Diseases: Molecular Mechanisms, Disease Relevance, and Therapeutic Potential.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Review
- A metabolite-bridged complex between SerRS and SIRT2 couples NAD⁺ metabolism to translation control.Nature communications · 2026Article
- Structural basis of SIRT2 pre-catalysis NADRSC chemical biology · 2025Article
- Efficient Crystallization of Apo Sirt2 for Small-Molecule Soaking and Structural Analysis of Ligand Interactions.Journal of medicinal chemistry · 2025Article
- Drugs Targeting Sirtuin 2 Exhibit Broad-Spectrum Anti-Infective Activity.Pharmaceuticals (Basel, Switzerland) · 2024Review
- Recent Advances in the Discovery of SIRT1/2 Inhibitors via Computational Methods: A Perspective.Pharmaceuticals (Basel, Switzerland) · 2024Review
- PROTACs Targeting Epigenetic Proteins.Acta materia medica · 2023Article
- An allosteric inhibitor of sirtuin 2 deacetylase activity exhibits broad-spectrum antiviral activity.The Journal of clinical investigation · 2023Article
- Golgi stress induces SIRT2 to counteract Shigella infection via defatty-acylation.Nature communications · 2022Article
- Mechanism-based inhibitors of SIRT2: structure-activity relationship, X-ray structures, target engagement, regulation of α-tubulin acetylation and inhibition of breast cancer cell migration.RSC chemical biology · 2021Article
- Sirtuin Oxidative Post-translational Modifications.Frontiers in physiology · 2021Review
- Simultaneous Inhibition of SIRT2 Deacetylase and Defatty-Acylase Activities via a PROTAC Strategy.ACS medicinal chemistry letters · 2020Article
- Dethioacylation by Sirtuins 1-3: Considerations for Drug Design Using Mechanism-Based Sirtuin Inhibition.ACS medicinal chemistry letters · 2020Article
- Nicotinamide inhibits melanoma in vitro and in vivo.Journal of experimental & clinical cancer research : CR · 2020Article
- Evolved, Selective Erasers of Distinct Lysine Acylations.Angewandte Chemie (International ed. in English) · 2020Article
- A Glycoconjugated SIRT2 Inhibitor with Aqueous Solubility Allows Structure-Based Design of SIRT2 Inhibitors.ACS chemical biology · 2019Article
- ABA/ASB structural biology session II 2018.Biophysical reviews · 2019Article
- Novel Lysine-Based Thioureas as Mechanism-Based Inhibitors of Sirtuin 2 (SIRT2) with Anticancer Activity in a Colorectal Cancer Murine Model.Journal of medicinal chemistry · 2019Article
- Article
- Identification of a novel small molecule that inhibits deacetylase but not defatty-acylase reaction catalysed by SIRT2.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2018Article
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Abstract
Sirtuins are NAD-dependent deacylases. Previous studies have established two important enzymatic intermediates in sirtuin-catalyzed deacylation, an alkylamidate intermediate I, which is then converted to a bicyclic intermediate II. However, how intermediate II is converted to products is unknown. Based on potent SIRT2-specific inhibitors we developed, here we report crystal structures of SIRT2 in complexes with a thiomyristoyl lysine peptide-based inhibitor and carba-NAD or NAD. Interestingly, by soaking crystals with NAD, we capture a distinct covalent catalytic intermediate (III) that is different from the previously established intermediates I and II. In this intermediate, the covalent bond between the S and the myristoyl carbonyl carbon is broken, and we believe this intermediate III to be the decomposition product of II en route to form the end products. MALDI-TOF data further support the intermediate III formation. This is the first time such an intermediate has been captured by X-ray crystallography and provides more mechanistic insights into sirtuin-catalyzed reactions.
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