Human sirtuins: Structures and flexibility

Lionel Sacconnay; Pierre-Alain Carrupt; Alessandra Nurisso

doi:10.1016/j.jsb.2016.10.008

Human sirtuins: Structures and flexibility

J Struct Biol. 2016 Dec;196(3):534-542. doi: 10.1016/j.jsb.2016.10.008. Epub 2016 Oct 20.

Authors

Lionel Sacconnay¹, Pierre-Alain Carrupt¹, Alessandra Nurisso²

Affiliations

¹ School of Pharmaceutical Sciences, University of Geneva, University of Lausanne, Rue Michel Servet 1, CH-1211 Geneva 4, Switzerland.
² 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.

PMID: 27773637
DOI: 10.1016/j.jsb.2016.10.008

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.

Keywords: Conformational changes; Modulators; Protein–protein interactions; Sirtuins; Structure-based drug design.

Publication types

Review
Research Support, Non-U.S. Gov't

MeSH terms

Aging*
Crystallography, X-Ray
Humans
Neoplasms / chemistry*
Neoplasms / drug therapy
Sirtuins / chemistry*
Sirtuins / ultrastructure

Substances

Sirtuins