Cysteine Proteases Of Hookworm Necator Americanus As Virulence Factors And Implications For Future Drug Design: A Bioinformatics-Based Study

Banerjee, A.

doi:10.1101/116921

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Cysteine Proteases Of Hookworm Necator Americanus As Virulence Factors And Implications For Future Drug Design: A Bioinformatics-Based Study

Banerjee, A.

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Abstract

Human hookworm Necator Americanus (NA) causes iron deficiency anemia, as the parasite ingests blood from the gastrointestinal tract of its human host. This bioinformatics-based study focuses on eight of the cathepsin B-like cysteine proteases (CPs) of the worm to explore their pathogenic potential. CP1 - CP6, which harbored the active site cysteine residue for enzymatic activity, were relevantly observed to have N-terminal signal peptide for extracellular localization. The secretory CPs could be releasing indigenous worm heparin at the host-pathogen interface for anticoagulation purposes. CP2 and CP3 showed a novel hemoglobinase motif that could be a prerequisite for hemoglobin degradation. CP1 and CP6 shared similar enzymatic-pocket features with cathepsin B and cruzain that cleave high molecular weight kininogen for blood-thinning activity. CP1, CP2, CP3, CP5 and CP6 were predicted to bind heparin, at their C terminal domain, like human cathepsin B and cruzain non-covalently bind heparin to enhance their activity. NA CPs action in concert with heparin, have implications for anti-heparin and heparin analog design against hookworm infection.

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Banerjee, A.. 2017-03-17. Cysteine Proteases Of Hookworm Necator Americanus As Virulence Factors And Implications For Future Drug Design: A Bioinformatics-Based Study. https://doi.org/10.1101/116921

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