Please use this identifier to cite or link to this item: https://www.arca.fiocruz.br/handle/icict/20986
Title: A Computational Methodology to Overcome the Challenges Associated With the Search for Specific Enzyme Targets to Develop Drugs Against Leishmania major
Authors: Catharina, Larissa
Lima, Carlyle Ribeiro
Franca, Alexander
Guimarães, Ana Carolina Ramos
Alves-Ferreira, Marcelo
Tuffery, Pierre
Derreumaux, Philippe
Carels, Nicolas
Affilliation: Instituto Nacional de Ciência e Tecnologia de Inovação em Doenças Negligenciadas. Rio de Janeiro, RJ, Brasil / Fundação Oswaldo Cruz. Centro de Desenvolvimento Tecnológico em Saúde. Rio de Janeiro, RJ, Brasil.
Université Paris 7. Centre National de la Recherche Scientifique (CNRS). Institut de Biologie Physico-Chimique (UPR 9080). Laboratoire de Biochimie Théorique. Paris, France / Université Paris Diderot. Institut National de la Santé et de la Recherche Médicale (INSERM). Molécules Thérapeutiques in silico (UMR-S 973). Paris, France.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Genômica Funcional e Bioinformática. Rio de Janeiro, Brazil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Genômica Funcional e Bioinformática. Rio de Janeiro, Brazil.
Fundação Oswaldo Cruz. Centro de Desenvolvimento Tecnológico em Saúde. Rio de Janeiro, RJ, Brasil.
Université Paris Diderot. Institut National de la Santé et de la Recherche Médicale (INSERM). Molécules Thérapeutiques in silico (UMR-S 973). Paris, France.
Université Paris 7. Centre National de la Recherche Scientifique (CNRS). Institut de Biologie Physico-Chimique (UPR 9080). Laboratoire de Biochimie Théorique. Paris, France.
Instituto Nacional de Ciência e Tecnologia de Inovação em Doenças Negligenciadas. Rio de Janeiro, RJ, Brasil / Fundação Oswaldo Cruz. Centro de Desenvolvimento Tecnológico em Saúde. Rio de Janeiro, RJ, Brasil.
Abstract: We present an approach for detecting enzymes that are specific of Leishmania major compared with Homo sapiens and provide targets that may assist research in drug development. This approach is based on traditional techniques of sequence homology comparison by similarity search and Markov modeling; it integrates the characterization of enzymatic functionality, secondary and tertiary protein structures, protein domain architecture, and metabolic environment. From 67 enzymes represented by 42 enzymatic activities classified by AnEnPi (Analogous Enzymes Pipeline) as specific for L major compared with H sapiens, only 40 (23 Enzyme Commission [EC] numbers) could actually be considered as strictly specific of L major and 27 enzymes (19 EC numbers) were disregarded for having ambiguous homologies or analogies with H sapiens. Among the 40 strictly specific enzymes, we identified sterol 24-C-methyltransferase, pyruvate phosphate dikinase, trypanothione synthetase, and RNA-editing ligase as 4 essential enzymes for L major that may serve as targets for drug development.
Keywords: Leishmaniasis
genomics
sequence homology
AnEnPi
specific enzymes
metabolism
keywords: Leishmaniose
genômica
Issue Date: 2017
Publisher: SAGE Publishing
Citation: CATHARINA, L. et al. A Computational Methodology to Overcome the Challenges Associated With the Search for Specific Enzyme Targets to Develop Drugs Against Leishmania major. Bioinform Biol Insights, v. 11, p. 1-21, 2017.
DOI: 10.1177/1177932217712471
ISSN: 11779322
Copyright: open access
Appears in Collections:CDTS - Artigos de Periódicos

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