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.
Kadam
Rameshwar U
RU
Centre of Pharmacoinformatics, National Institute of Pharmaceutical Education and Research, Sector 67, S.A.S Nagar-160062, Punjab, IndiaIBMC, Instituto de Biologia Molecular e Celular da Universidade do Porto, PortugalFaculdade de Farmacia da Universidade do Porto, PortugalINSERM, Institut National de la Santé et de la Recherche Médicale, FranceIRD, UR008 'Pathogenie des Trypanosomatides', 911 Avenue Agropolis, BP 64501, 34394 Montpellier Cedex 5, France.
Tavares
Joana
J
Centre of Pharmacoinformatics, National Institute of Pharmaceutical Education and Research, Sector 67, S.A.S Nagar-160062, Punjab, IndiaIBMC, Instituto de Biologia Molecular e Celular da Universidade do Porto, PortugalFaculdade de Farmacia da Universidade do Porto, PortugalINSERM, Institut National de la Santé et de la Recherche Médicale, FranceIRD, UR008 'Pathogenie des Trypanosomatides', 911 Avenue Agropolis, BP 64501, 34394 Montpellier Cedex 5, France.
M
Kiran V
KV
Centre of Pharmacoinformatics, National Institute of Pharmaceutical Education and Research, Sector 67, S.A.S Nagar-160062, Punjab, IndiaIBMC, Instituto de Biologia Molecular e Celular da Universidade do Porto, PortugalFaculdade de Farmacia da Universidade do Porto, PortugalINSERM, Institut National de la Santé et de la Recherche Médicale, FranceIRD, UR008 'Pathogenie des Trypanosomatides', 911 Avenue Agropolis, BP 64501, 34394 Montpellier Cedex 5, France.
Cordeiro
Anabela
A
Centre of Pharmacoinformatics, National Institute of Pharmaceutical Education and Research, Sector 67, S.A.S Nagar-160062, Punjab, IndiaIBMC, Instituto de Biologia Molecular e Celular da Universidade do Porto, PortugalFaculdade de Farmacia da Universidade do Porto, PortugalINSERM, Institut National de la Santé et de la Recherche Médicale, FranceIRD, UR008 'Pathogenie des Trypanosomatides', 911 Avenue Agropolis, BP 64501, 34394 Montpellier Cedex 5, France.
Ouaissi
Ali
A
Centre of Pharmacoinformatics, National Institute of Pharmaceutical Education and Research, Sector 67, S.A.S Nagar-160062, Punjab, IndiaIBMC, Instituto de Biologia Molecular e Celular da Universidade do Porto, PortugalFaculdade de Farmacia da Universidade do Porto, PortugalINSERM, Institut National de la Santé et de la Recherche Médicale, FranceIRD, UR008 'Pathogenie des Trypanosomatides', 911 Avenue Agropolis, BP 64501, 34394 Montpellier Cedex 5, France.
Roy
Nilanjan
N
Centre of Pharmacoinformatics, National Institute of Pharmaceutical Education and Research, Sector 67, S.A.S Nagar-160062, Punjab, IndiaIBMC, Instituto de Biologia Molecular e Celular da Universidade do Porto, PortugalFaculdade de Farmacia da Universidade do Porto, PortugalINSERM, Institut National de la Santé et de la Recherche Médicale, FranceIRD, UR008 'Pathogenie des Trypanosomatides', 911 Avenue Agropolis, BP 64501, 34394 Montpellier Cedex 5, France.
D000818:Animals; D000981:Antiprotozoal Agents / Q000737:chemistry*; D001665:Binding Sites; D020134:Catalytic Domain; D016923:Cell Death; D004353:Drug Evaluation, Preclinical; D004791:Enzyme Inhibitors / Q000737:chemistry; D006801:Humans; D007891:Leishmania / Q000187:drug effects / Q000201:enzymology*; D021281:Quantitative Structure-Activity Relationship; D037761:Sirtuins / Q000037:antagonists & inhibitors* / Q000378:metabolism
D000981:Antiprotozoal Agents; D004791:Enzyme Inhibitors; D037761:Sirtuins