title: Human sirtuins: Structures and flexibility.
abstract: In recent years, sirtuins (SIRTs), members of histone deacetylases (HDACs) class III, have been found to modulate cellular processes related to the development of human aging-related pathologies (i.e. cancer, neurodegeneration, metabolic disorders). Several crystallographic structures and computational studies have shed light into their catalytic mechanism of action, identifying also the structural elements for the design of selective drug candidates. In this review, we first aim at summarizing the structural features characterizing human SIRTs. We then describe the observed mass and one-off movements related to conformational changes upon SIRT-mediated recognition events. Such information will be useful not only for rationalizing the design of new SIRT modulators, but also for improving the comprehension of SIRT-related biological roles.
authors: School of Pharmaceutical Sciences, University of Geneva, University of Lausanne, Rue Michel Servet 1, CH-1211 Geneva 4, Switzerland.
authors: Lionel
authors: L
authors: Sacconnay
authors: School of Pharmaceutical Sciences, University of Geneva, University of Lausanne, Rue Michel Servet 1, CH-1211 Geneva 4, Switzerland.
authors: Pierre-Alain
authors: PA
authors: Carrupt
authors: School of Pharmaceutical Sciences, University of Geneva, University of Lausanne, Rue Michel Servet 1, CH-1211 Geneva 4, Switzerland; Département de Biochimie, Université de Montréal, H3C 3J7 Montréal, Québec, Canada.
authors: Alessandra
authors: A
authors: Nurisso
mesh_terms: D000375:Aging; D018360:Crystallography, X-Ray; D006801:Humans; D009369:Neoplasms / Q000737:chemistry* / Q000188:drug therapy; D037761:Sirtuins / Q000737:chemistry* / Q000648:ultrastructure
chemical_list: D037761:Sirtuins
keywords: Conformational changes; Modulators; Protein–protein interactions; Sirtuins; Structure-based drug design