Journal
MICROORGANISMS
Volume 10, Issue 2, Pages -Publisher
MDPI
DOI: 10.3390/microorganisms10020231
Keywords
GDP-mannose pyrophosphorylase; Leishmania infantum; enzyme properties
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Leishmaniasis is a vector-borne disease with limited treatment options. GDP-mannose pyrophosphorylase (GDP-MP) has been identified as a potential therapeutic target for the development of new antileishmanial drugs. In this study, the enzymatic properties of recombinant L. infantum GDP-MP (LiGDP-MP) were analyzed, revealing a mutation at position 258 compared to the homolog in L. donovani. Further studies are needed to determine the significance of this residue change for L. infantum.
Background: Leishmaniasis, a vector-borne disease caused by the protozoan parasite from the genus Leishmania, is endemic to tropical and subtropical areas. Few treatments are available against leishmaniasis, with all presenting issues of toxicity, resistance, and/or cost. In this context, the development of new antileishmanial drugs is urgently needed. GDP-mannose pyrophosphorylase (GDP-MP), an enzyme involved in the mannosylation pathway, has been described to constitute an attractive therapeutic target for the development of specific antileishmanial agents. Methods: In this work, we produced, purified, and analyzed the enzymatic properties of the recombinant L. infantum GDP-MP (LiGDP-MP), a single leishmanial GDP-MP that presents mutation of an aspartate instead of an alanine at position 258, which is also the single residue difference with the homolog in L. donovani: LdGDP-MP. Results: The purified LiGDP-MP displayed high substrate and cofactor specificities, a sequential random mechanism of reaction, and the following kinetic constants: V-m at 0.6 mu M center dot min(-1), K-m from 15-18 mu M, k(cat) from 12.5-13 min(-1), and k(cat)/K-m at around 0.8 min(-1)mu M-1. Conclusions: These results show that LiGDP-MP has similar biochemical and enzymatic properties to LdGDP-MP. Further studies are needed to determine the advantage for L. infantum of the A258D residue change in GDP-MP.
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