Structure function analysis of Leishmania sirtuin: an ensemble of in silico and biochemical studies.

Novel anti-leishmanial target LmSir2 has few subtle but prudent structural differences in ligand binding and catalytic domain as compared to its human counterpart. In silico screening and validation followed by in vitro deacetylation and cell killing assays described herein give a proof of concept for development of strategies exploiting such minor differences for screening libraries of small molecules to identify selective inhibitors.

Comparative protein modeling and surface analysis of Leishmania sirtuin: A potential target for antileishmanial drug discovery.

Homology model of Leishmania SIR2 shed new light on the ligand binding features of this enzyme. The molecular electrostatic potentials (MESP), the cavity depth analysis, and LmSIR2-hSIRT2 models' superposition suggested that the nicotinamide binding catalytic domain has several minor but potentially important structural differences. These differences could be exploited for designing antileishmanial compounds.