guanosine-diphosphate-mannose and Leishmaniasis--Visceral

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.

Topics: Amino Acid Motifs; Amino Acid Sequence; Animals; Antiprotozoal Agents; Consensus Sequence; Dogs; Drug Design; Glycosylation; Guanosine Diphosphate Mannose; Host-Parasite Interactions; Humans; Leishmania infantum; Leishmaniasis, Visceral; Models, Molecular; Molecular Conformation; Nucleotidyltransferases; Sequence Alignment; Species Specificity