In silico analysis of a therapeutic target in Leishmania infantum: the guanosine-diphospho-D-mannose pyrophosphorylase |
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Authors: | Pomel S Rodrigo J Hendra F Cavé C Loiseau P M |
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Affiliation: | Université Paris-Sud 11, UMR 8076 CNRS, Chimiothérapie Antiparasitaire, 5, rue Jean-Baptiste Clément, 92296 Chatenay-Malabry, France. |
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Abstract: | Leishmaniases are tropical and sub-tropical diseases for which classical drugs (i.e. antimonials) exhibit toxicity and drug resistance. Such a situation requires to find new chemical series with antileishmanial activity. This work consists in analyzing the structure of a validated target in Leishmania: the GDP-mannose pyrophosphorylase (GDP-MP), an enzyme involved in glycosylation and essential for amastigote survival. By comparing both human and L. infantum GDP-MP 3D homology models, we identified (i) a common motif of amino acids that binds to the mannose moiety of the substrate and, interestingly, (ii) a motif that is specific to the catalytic site of the parasite enzyme. This motif could then be used to design compounds that specifically inhibit the leishmanial GDP-MP, without any effect on the human homolog. |
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Keywords: | Leishmania infantum GDP-mannose pyrophosphorylase antileishmanial activity |
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