ArticleMolecular cell2007
Structural basis for nicotinamide inhibition and base exchange in Sir2 enzymes.
Article in Molecular cell, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
30 citing papers in PubMed, 65 citations in OpenAlex.
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- YZL-51N functions as a selective inhibitor of SIRT7 by NADiScience · 2024Article
- carba Nicotinamide Adenine Dinucleotide Phosphate: Robust Cofactor for Redox Biocatalysis.Angewandte Chemie (International ed. in English) · 2021Article
- Structural and functional evidence of bacterial antiphage protection by Thoeris defense system via NADNature communications · 2020Article
- Deacylation Mechanism by SIRT2 Revealed in the 1'-SH-2'-O-Myristoyl Intermediate Structure.Cell chemical biology · 2017Article
- Article
- Physical nature of intermolecular interactions inside Sir2 homolog active site: molecular dynamics and ab initio study.Journal of molecular modeling · 2016Article
- Histone Deacetylases and Their Inhibition in Candida Species.Frontiers in microbiology · 2016Review
- Emerging role of silent information regulator 1 (SIRT1) in hepatocellular carcinoma: a potential therapeutic target.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2015Review
- Acetylation of TUG protein promotes the accumulation of GLUT4 glucose transporters in an insulin-responsive intracellular compartment.The Journal of biological chemistry · 2015Article
- Insight into the Mechanism of Intramolecular Inhibition of the Catalytic Activity of Sirtuin 2 (SIRT2).PloS one · 2015Article
- Structural and functional analysis of human SIRT1.Journal of molecular biology · 2014Article
- Sirtuin-3 (SIRT3), a therapeutic target with oncogenic and tumor-suppressive function in cancer.Cell death & disease · 2014Review
- Modulation of epigenetic targets for anticancer therapy: clinicopathological relevance, structural data and drug discovery perspectives.Current pharmaceutical design · 2013Review
- Structural basis for sirtuin activity and inhibition.The Journal of biological chemistry · 2012Review
- Selective small molecule inhibition of poly(ADP-ribose) glycohydrolase (PARG).ACS chemical biology · 2012Article
- Article
- A role for histone H4K16 hypoacetylation in Saccharomyces cerevisiae kinetochore function.Genetics · 2011Article
- Acetate supplementation increases brain histone acetylation and inhibits histone deacetylase activity and expression.Molecular and cellular biochemistry · 2011Article
- Structure and biochemical functions of SIRT6.The Journal of biological chemistry · 2011Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
The Sir2 family of proteins consists of broadly conserved NAD(+)-dependent deacetylases that are implicated in diverse biological processes, including DNA regulation, metabolism, and longevity. Sir2 proteins are regulated in part by the cellular concentrations of a noncompetitive inhibitor, nicotinamide, that reacts with a Sir2 reaction intermediate via a base-exchange reaction to reform NAD(+) at the expense of deacetylation. To gain a mechanistic understanding of nicotinamide inhibition in Sir2 enzymes, we captured the structure of nicotinamide bound to a Sir2 homolog, yeast Hst2, in complex with its acetyl-lysine 16 histone H4 substrate and a reaction intermediate analog, ADP-HPD. Together with related biochemical studies and structures, we identify a nicotinamide inhibition and base-exchange site that is distinct from the so-called "C pocket" binding site for the nicotinamide group of NAD(+). These results provide insights into the Sir2 mechanism of nicotinamide inhibition and have important implications for the development of Sir2-specific effectors.
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What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.