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Bioinform Biol Insights. 2017 Jun 12;11:1177932217712471. doi: 10.1177/1177932217712471. eCollection 2017.

A Computational Methodology to Overcome the Challenges Associated With the Search for Specific Enzyme Targets to Develop Drugs Against Leishmania major.

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Laboratório de Modelagem de Sistemas Biológicos, Instituto Nacional de Ciência e Tecnologia de Inovação em Doenças de Populações Negligenciadas (INCT-IDPN), Centro de Desenvolvimento Tecnológico em Saúde (CDTS), Fundação Oswaldo Cruz (Fiocruz), Rio de Janeiro, Brazil.
Laboratoire de Biochimie Théorique, Institut de Biologie Physico-Chimique (UPR 9080), Centre National de la Recherche Scientifique (CNRS), Université Paris 7, Paris, France.
Molécules Thérapeutiques in silico (UMR-S 973), Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris Diderot, Sorbonne Paris Cité, Paris, France.
Laboratório de Genômica Funcional e Bioinformática, Instituto Oswaldo Cruz (IOC), Fundação Oswaldo Cruz (Fiocruz), Rio de Janeiro, Brazil.


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.


AnEnPi; Leishmaniasis; genomics; metabolism; sequence homology; specific enzymes

Conflict of interest statement

DECLARATION OF CONFLICTING INTERESTS: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

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