Author | Sacconnay, Lionel | |
Author | Smirlis, Despina | |
Author | Queiroz, Emerson Ferreira | |
Author | Wolfender, Jean-Luc | |
Author | Soares, Milena Botelho Pereira | |
Author | Carrupta, Pierre-Alain | |
Author | Nurisso, Alessandra | |
Access date | 2014-10-09T12:36:36Z | |
Available date | 2014-10-09T12:36:36Z | |
Document date | 2013 | |
Citation | SACCONAY, L. et al. Structural insights of SIR2rp3 proteins as promising biotargets to fight against Chagas disease and leishmaniasis. Molecular Biosysttems, v. 9, n. 9, p. 2223-2230, 2013. | pt_BR |
ISSN | 1742-2051 | |
URI | https://www.arca.fiocruz.br/handle/icict/8560 | |
Language | eng | pt_BR |
Publisher | The Royal Society of Chemistry | pt_BR |
Rights | open access | pt_BR |
Title | Structural insights of SIR2rp3 proteins as promising biotargets to fight against Chagas disease and leishmaniasis | pt_BR |
Type | Article | pt_BR |
DOI | 10.1039/c3mb70180h | |
Abstract | Trypanosoma cruzi and Leishmania spp. are protozoan pathogens responsible for Chagas disease and leishmaniasis, respectively. Current therapies rely only on a very small number of drugs, most of them are inadequate because of their severe host toxicity or drug-resistance phenomena. In order to find therapeutic alternatives, the identification of new biotargets is highly desired. In this study, homology modelling, docking and molecular dynamics simulations have been used to generate robust 3D models of NAD(+)-dependent deacetylases from Trypanosoma and Leishmania spp., known as SIR2rp3, whose structures have never been described before. Molecular docking of known inhibitors revealed strong analogies with the mitochondrial human SIRT5 in terms of binding mode and interaction strength. On the other hand, by extending the analysis to the channel rims, regions of difference between host and parasitic targets, useful for future selective drug design projects, were pointed out. | pt_BR |
Affilliation | University of Geneva. University of Lausanne. Pharmacochemistry and Phytochemistry & Bioactive Natural Products. School of Pharmaceutical Sciences. Geneva, Switzerland | pt_BR |
Affilliation | Hellenic Pasteur Institute. Laboratory of Molecular Parasitology. Microbiology Dept. Athens, Greece | pt_BR |
Affilliation | University of Geneva. University of Lausanne. Pharmacochemistry and Phytochemistry & Bioactive Natural Products. School of Pharmaceutical Sciences. Geneva, Switzerland | pt_BR |
Affilliation | University of Geneva. University of Lausanne. Pharmacochemistry and Phytochemistry & Bioactive Natural Products. School of Pharmaceutical Sciences. Geneva, Switzerland | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Salvador, BA, Brasil / Hospital São Rafael. Salvador, BA, Brazil | pt_BR |
Affilliation | University of Geneva. University of Lausanne. Pharmacochemistry and Phytochemistry & Bioactive Natural Products. School of Pharmaceutical Sciences. Geneva, Switzerland | pt_BR |
Affilliation | University of Geneva. University of Lausanne. Pharmacochemistry and Phytochemistry & Bioactive Natural Products. School of Pharmaceutical Sciences. Geneva, Switzerland | pt_BR |
DeCS | Inibidores Enzimáticos/química | pt_BR |
DeCS | Modelos Moleculares | pt_BR |
DeCS | Sirtuína 2/química | pt_BR |
DeCS | Sequência de Aminoácidos | pt_BR |
DeCS | Doença de Chagas | pt_BR |
DeCS | Inibidores Enzimáticos/farmacologia | pt_BR |
DeCS | Humanos | pt_BR |
DeCS | Leishmaniose | pt_BR |
DeCS | Proteínas Mitocondriais/antagonistas & inibidores | pt_BR |
DeCS | Simulação de Acoplamento Molecular | pt_BR |
DeCS | Simulação de Dinâmica Molecular | pt_BR |
DeCS | Dados de Sequência Molecular | pt_BR |
DeCS | Conformação Proteica | pt_BR |
DeCS | Alinhamento de Sequência | pt_BR |
DeCS | Sirtuína 2/antagonistas & inibidores | pt_BR |
DeCS | Trypanosoma cruzi/metabolismo | pt_BR |