Investigation on the sucrose binding pocket of HIV-1 Integrase by molecular dynamics and synergy experiments

Author(s)
Cristina Tintori, Francesca Esposito, Francesca Morreale, Riccardo Martini, Enzo Tramontano, Maurizio Botta
Abstract

Enzymes whose catalytic activity depends on multimeric assembly are targets for inhibitors that perturb the interactions between the protein subunits such as the HIV-1 Integrase (IN). Sucrose has been recently crystallized in complex with IN revealing an allosteric binding pocket at the monomer-monomer interface. Herein, molecular dynamics were applied to theoretically test the effect of this small ligand on IN. As a result, such a compound increases the mutual free energy of binding between the two interacting monomers. Biological experiments confirmed the computational forecast.

Organisation(s)
External organisation(s)
Università Degli Studi di Siena, Università degli Studi di Cagliari, Università degli Studi di Messina, Temple University, Philadelphia
Journal
Bioorganic & Medicinal Chemistry Letters
Volume
25
Pages
3013-3016
No. of pages
4
ISSN
0960-894X
DOI
https://doi.org/10.1016/j.bmcl.2015.05.011
Publication date
08-2015
Peer reviewed
Yes
Austrian Fields of Science 2012
301207 Pharmaceutical chemistry
Keywords
ASJC Scopus subject areas
Drug Discovery, Molecular Medicine, Molecular Biology, Biochemistry, Clinical Biochemistry, Pharmaceutical Science, Organic Chemistry
Sustainable Development Goals
SDG 3 - Good Health and Well-being
Portal url
https://ucris.univie.ac.at/portal/en/publications/investigation-on-the-sucrose-binding-pocket-of-hiv1-integrase-by-molecular-dynamics-and-synergy-experiments(505e2fc8-73c4-4601-b480-979ed3a15ccd).html