Abstract
Human hookworm Necator Americanus causes iron deficiency anemia, as the parasite ingests blood from the gastrointestinal tract of its human host. The virulence factors of this blood feeding nematode have not been researched extensively. This bioinformatics based study focuses on eight of the cathepsin B like cysteine proteases (CPs) of the worm, which could have immense pathogenic potential. The role of the individual CPs remain vaguely determined except for CP3 which has been shown to act as globinase in the hemoglobin degradation pathway. In this study, the cysteine proteases were subjected to predictive molecular characterizations viz: probability of extracellular secretion to the interface between pathogen and host, ability for hemoglobin degradation, and/or interaction with host plasma proteins. CP1 - CP6, which harbored the active site cysteine and were observed to have N terminal signal peptide for extracellular localization, were relevantly predicted to be secretory. Amongst these, CP2 and CP3 showed the presence of hemoglobinase motif derived in this study that could be a prerequisite for globin or hemoglobin degradation. Similar S2 subsite feature of CP1 and CP6 that is shared with cruzain and cathepsin B is suggestive of involvement of the hookworm CPs in binding HMWK as substrate CP1, CP2, CP3, CP5 and CP6 were predicted to bind heparin, which is the glycosaminoglycan molecule that has been demonstrated to aid the substrate-cleaving functionality of other cysteine proteases like human cathepsin B and cruzain. Heparin docked onto the NA CPs at the C terminal domain, away from the active site, similar to what has been shown for heparin binding to cathepsin B and cruzain. These observations therefore lead us to the hypothesize that the functions of the hookworm CPs, which could include preventing blood clot formation, might be assisted by heparin. This study underscores the potential of synthetic heparin analogs as molecular treatment for hookworm infection, which could have implications for future drug design.
- NA
- Necator Americanus
- CPs
- Cysteine proteases.
- SmSP1
- Schistosoma mansoni Serine Protease 1
- HMWK
- High Molecular Weight Kininogen
- T.Cruzi
- Trypanosoma Cruzi
- S.mansoni
- Schistosoma mansoni
- P.falciparum
- Plasmodium falciparum
- P.Westermani
- Paragonimus westermani
- C. elegans
- Caenorhabditis elegans
- L. major
- Leishmania major
- A. Caninum
- Ancylostoma caninum
- S.japonicum
- Schistosoma japonicum
- H. Contortus
- Haemonchus contortus
- O. ostertagi
- Ostertagia ostertagi
- A. Suum
- Ascaris suum