Lipophosphoglycan 3 From Leishmania infantum chagasi Binds Heparin With Micromolar Affinity

Abstract

Leishmania infantum chagasi is an intracellular protozoan parasite responsible for visceral leishmaniasis, a fatal disease in humans. Heparin-binding proteins (HBPs) are proteins that bind to carbohydrates present in glycoproteins or glycolipids. Evidence suggests that HBPs present on Leishmania surface participate in the adhesion and invasion of parasites to tissues of both invertebrate and vertebrate hosts. In this study, we identified the product with an HSP90 (heat shock protein 90) domain encoded by lipophosphoglycan (LPG3) gene as a L infantum chagasi HBP (HBPLc). Structural analysis using the LPG3 recombinant protein suggests that it is organized as a tetramer. Binding analysis confirms that it is capable of binding heparin with micromolar affinity. Inhibition of adenosine triphosphatase activity in the presence of heparin, molecular modeling, and in silico docking analysis suggests that heparin-binding site superimposes with the adenosine triphosphate–binding site. Together, these results show new properties of LPG3 and suggest an important role in leishmaniasis.

An immunoinformatic approach driven by experimental proteomics: in silico design of a subunit candidate vaccine targeting secretory proteins of Leishmania donovani amastigotes

“…Prediction on IFN-γ induction capacity revealed a total of 117 epitopes (15-mer) with positive scores. This heparin binding [128,129] Immunogenic in vivo and immunoreactive in sera of human (L.…”

Imidazolium salts as an alternative for anti-Leishmania drugs: Oxidative and immunomodulatory activities

“…To elucidate possible mechanisms of action of IS on Leishmania parasites, membrane and mitochondrial dysfunctions, ROS generation and morphological changes in response to IS were investigated. In Leishmania , mitochondria are a drug target ( 36 ), since this unique organelle is the main site of ROS production, and excessive ROS may lead to oxidative stress, which may be one of the major contributors to cell death by IS ( 37 , 38 ). In addition, the maintenance of an appropriate mitochondrial membrane potential (ΔΨm) is essential for Leishmania survival ( 36 , 37 ).…”

Extracellular Vesicles Released by Leishmania (Leishmania) amazonensis Promastigotes with Distinct Virulence Profile Differently Modulate the Macrophage Functions

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