Interactomic and pharmacological insights on human Sirt-1

Ankush Sharma, Vasu Gautam, Susan Costantini, Antonella Paladino, Giovanni Colonna

Research output: Contribution to journalArticle

Abstract

Sirt-1 is defined as a nuclear protein involved in the molecular mechanisms of inflammation and neurodegeneration through the deacetylation of many different substrates even if experimental data in mouse suggest both its cytoplasmatic presence and nucleocytoplasmic shuttling upon oxidative stress. Since the experimental structure of human Sirt-1 has not yet been reported, we have modeled its 3D structure, highlighted that it is composed by four different structural regions: N-terminal region, allosteric site, catalytic core and C-terminal region, and underlined that the two terminal regions have high intrinsic disorder propensity and numerous putative phosphorylation sites. Many different papers report experimental studies related to its functional activators because Sirt-1 is implicated in various diseases and cancers.The aim of this article is (i) to present interactomic studies based human Sirt-1 to understand its most important functional relationships in the light of the gene-protein interactions that control major metabolic pathways and (ii) to show by docking studies how this protein binds some activator molecules in order to evidence structural determinants, physico-chemical features and those residues involved in the formation of complexes.

Original languageEnglish
Article numberArticle 40
JournalFrontiers in Pharmacology
Volume3 MAR
DOIs
Publication statusPublished - 2012

Keywords

  • Activators
  • Interaction map
  • Interactome
  • Molecular docking
  • Sirt-1

ASJC Scopus subject areas

  • Pharmacology (medical)
  • Pharmacology

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    Sharma, A., Gautam, V., Costantini, S., Paladino, A., & Colonna, G. (2012). Interactomic and pharmacological insights on human Sirt-1. Frontiers in Pharmacology, 3 MAR, [Article 40]. https://doi.org/10.3389/fphar.2012.00040