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Pant, Akansha
- Targeting Allosteric Site of Enzyme: New Approach to Overcoming Drug Resistance Problem in Malaria
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1 ICMR-National Institute of Malaria Research, Dwarka Sector 8, New Delhi, IN
2 Department of Biochemistry, ICMR-National Institute for Research in Environmental Health, Bhopal, MP - 462001, IN
1 ICMR-National Institute of Malaria Research, Dwarka Sector 8, New Delhi, IN
2 Department of Biochemistry, ICMR-National Institute for Research in Environmental Health, Bhopal, MP - 462001, IN
Source
The Indian Practitioner, Vol 72, No 2 (2019), Pagination: 17-22Abstract
Haemoglobin degradation is essential for parasite growth and development performed by the cascade of proteases. Falcipains, the cysteine protease of malaria parasite, act as major hemoglobinases. They consist of bipartite pro- and mature domains that interact via ‘hot-spot’ and retain the structural integrity of the enzyme in an inactive state. Upon sensing the acidic conditions, the hot-spot interactions dissociate and release mature active enzyme. To inhibit falcipains, several active site compounds exist, however, inhibitors that target it via allosteric mechanism remain unexplored. Recently characterized allosteric inhibitors, NA-01 & NA-03, arrest the parasite growth by specifically blocking the auto-processing event in falcipains. Inhibitors showed high affinity for enzymes in the presence of the prodomain without affecting the secondary structure. Our group published the first report in malaria where allosteric inhibitors blocked the autoprocessing event in parasite proteases. Targeting allosteric sites in falcipains can serve as a new mechanismbased approach in malaria, which could be less vulnerable to the drug resistance.Keywords
Allosteric site Inhibitor, Auto-processing, Falcipains, Cysteine Proteases, Malaria.
References
- WHO | World malaria report 2018. WHO (2018). doi:http:// www.who.int/malaria/publications/world-malaria-report2017/report/en/
- Dash, A. P., Valecha, N., Anvikar, A. R. & Kumar, A. Malaria in India: Challenges and opportunities. Journal of Biosciences (2008). doi:10.1007/s12038-008-0076-x
- Imwong, M. et al. The spread of artemisinin-resistant Plasmodium falciparum in the Greater Mekong subregion: a molecular epidemiology observational study. Lancet Infect. Dis. (2017). doi:10.1016/S1473-3099(17)30048-8
- Cui, L. et al. Malaria in the Greater Mekong Subregion: Heterogeneity and complexity. Acta Trop. (2012). doi:10.1016/j.actatropica.2011.02.016
- Otsuji, N., World Health Organization, Fallis, A. ., Subregion, G. M. & WHO. Emergency response to artemisinin resistance in the greater Mekong subregion. J. Chem. Inf. Model. (2013). doi:10.1017/CBO9781107415324.004
- Woodrow, C. J. & White, N. J. The clinical impact of artemisinin resistance in Southeast Asia and the potential for future spread. FEMS Microbiology Reviews (2017). doi:10.1093/femsre/ fuw037
- Mita, T., Tachibana, S. I., Hashimoto, M. & Hirai, M. Plasmodium falciparum kelch 13: A potential molecular marker for tackling artemisinin-resistant malaria parasites. Expert Review of Anti-Infective Therapy (2016). doi:10.1586/147 87210.2016.1106938
- Mishra, N. et al. Emerging polymorphisms in falciparum Kelch 13 gene in Northeastern region of India. Malar. J. (2016). doi:10.1186/s12936-016-1636-4
- Breglio, K. F. et al. A single nucleotide polymorphism in the Plasmodium falciparum atg18 gene associates with artemisinin resistance and confers enhanced parasite survival under nutrient deprivation. Malar. J. (2018). doi:10.1186/s12936018-2532-x
- Siddiqui, F. A. et al. Plasmodium falciparum Falcipain-2a Polymorphisms in Southeast Asia and Their Association With Artemisinin Resistance. J. Infect. Dis. (2018). doi:10.1093/ infdis/jiy188
- Demas, A. R. et al. Mutations in Plasmodium falciparum actin-binding protein coronin confer reduced artemisinin susceptibility. Proc. Natl. Acad. Sci. (2018). doi:10.1073/ pnas.1812317115
- Wilby, K. J., Lau, T. T. Y., Gilchrist, S. E. & Ensom, M. H. H. Mosquirix (RTS,S): A novel vaccine for the prevention of Plasmodium falciparum malaria. Ann. Pharmacother. (2012). doi:10.1345/aph.1Q634
- Casares, S., Brumeanu, T. D. & Richie, T. L. The RTS, S malaria vaccine. Vaccine28, 4880–4894 (2010).
- Rosenthal, P. J. Cysteine proteases of malaria parasites. Int. J. Parasitol.34, 1489– 1499 (2004).
- Gardner, M. J. et al. Genome sequence of the human malaria parasite Plasmodium falciparum. Nature (2002). doi:10.1038/ nature01097
- Sajid, M. & McKerrow, J. H. Cysteine proteases of parasitic organisms. Mol. Biochem. Parasitol.120, 1–21 (2002).
- Rosenthal, P. J., McKerrow, J. H., Aikawa, M., Nagasawa, H. & Leech, J. H. A malarial cysteine proteinase is necessary for hemoglobin degradation by Plasmodium falciparum. J. Clin. Invest.82, 1560–1566 (1988).
- Pant, A. et al. Proteases in Mosquito Borne Diseases : New Avenues in Drug Development. 1–12 (2017). doi:10.2174/15680 26617666170130
- Banerjee, R. et al. Four plasmepsins are active in the Plasmodium falciparum food vacuole, including a protease with an active-site histidine. Proc. Natl. Acad. Sci. (2002). doi:10.1073/pnas.022630099
- Francis, S. E., Sullivan, D. J. & Goldberg, and D. E. Hemoglobin Metabolism In The Malaria Parasite Plasmodium Falciparum. Annu. Rev. Microbiol. (1997). doi:10.1146/annurev.micro.51.1.97
- Liu, J., Istvan, E. S., Gluzman, I. Y., Gross, J. & Goldberg, D. E. Plasmodium falciparum ensures its amino acid supply with multiple acquisition pathways and redundant proteolytic enzyme systems. Proc. Natl. Acad. Sci.103, 8840–8845 (2006).
- Goldberg, D. E. Hemoglobin degradation in the human malaria pathogen Plasmodium falciparum: a catabolic pathway initiated by a specific aspartic protease. J. Exp. Med. (1991). doi:10.1084/jem.173.4.961
- Tanaka, T. Q. et al. Plasmodium dipeptidyl aminopeptidases as malaria transmissionblocking drug targets. Antimicrob. Agents Chemother. (2013). doi:10.1128/AAC.02495-12
- Sijwali, P. S., Koo, J., Singh, N. & Rosenthal, P. J. Gene disruptions demonstrate independent roles for the four falcipain cysteine proteases of Plasmodium falciparum. Mol. Biochem. Parasitol.150, 96–106 (2006).
- Wang, S. X. et al. Structural basis for unique mechanisms of folding and hemoglobin binding by a malarial protease. Proc. Natl. Acad. Sci. U. S. A.103, 11503–11508 (2006).
- Subramanian, S., Sijwali, P. S. & Rosenthal, P. J. Falcipain Cysteine Proteases Require Bipartite Motifs for Trafficking to the Plasmodium falciparum Food Vacuole * □. 282, 24961– 24969 (2007).
- Sundararaj, S. et al. The Ionic and Hydrophobic Interactions Are Required for the Auto Activation of Cysteine Proteases of Plasmodium falciparum. PLoS One7, (2012).
- Kerr, I. D. et al. Vinyl sulfones as antiparasitic agents and a structural basis for drug design. J. Biol. Chem.284, 25697– 25703 (2009).
- Bailly, E., Jambou, R., Savel, J. & Jaureguiberry, G. Plasmodium falciparum: Differential Sensitivity In Vitro to E‐64 (Cysteine Protease Inhibitor) and Pepstatin A (Aspartyl Protease Inhibitor). J. Protozool.39, 593–599 (1992).
- Singh, A. K. et al. Design, synthesis and biological evaluation of functionalized phthalimides: A new class of antimalarials and inhibitors of falcipain-2, a major hemoglobinase of malaria parasite. Bioorganic Med. Chem.23, 1817–1827 (2015).
- McKerrow, J. H., Caffrey, C., Kelly, B., Loke, P. & Sajid, M. Proteases In Parasitic Diseases. Annu. Rev. Pathol. Mech. Dis. (2006). doi:10.1146/annurev.pathol.1.110304.100151
- Mckerrow, J. H., Sun, E., Rosenthal, P. J. & Bouvier, J. The Proteases And L Par). Sitic Protozoa. (1993).
- Sundararaj, S. et al. Cross-talk between malarial cysteine proteases and falstatin: The BC loop as a hot-spot target. PLoS One9, (2014).
- Benson, L. E., Siegel, A. J., Lynch, R. E., Colwell, E. J. & Canby, J. P. Drug Resistance In Malaria. The Lancet (1972). doi:10.1016/S01406736(72)90251-6
- Peterson, D. S., Milhous, W. K. & Wellems, T. E. Molecular basis of differential resistance to cycloguanil and pyrimethamine in Plasmodium falciparum malaria. Proc. Natl. Acad. Sci. U. S. A.87, 3018–22 (1990).
- Peterson, D. S., Walliker, D. & Wellems, T. E. Evidence that a point mutation in dihydrofolate reductase-thymidylate synthase confers resistance to pyrimethamine in falciparum malaria. Proc. Natl. Acad. Sci. U. S. A.85, 9114–8 (1988).
- Verespy, S., Mehta, A. Y., Afosah, D., Al-Horani, R. A. & Desai, U. R. Allosteric Partial Inhibition of Monomeric Proteases. Sulfated Coumarins Induce Regulation, not just Inhibition, of Thrombin. Sci. Rep. (2016). doi:10.1038/ srep24043
- Iii, S. V., Mehta, A. Y., Afosah, D., Al-horani, R. A. & Desai, U. R. Allosteric Partial Inhibition of Monomeric Proteases . Sulfated Coumarins Induce Regulation , not just Inhibition, of Thrombin. Nat. Publ. Gr. 1–13 (2016). doi:10.1038/ srep24043
- Scannevin, R. H. et al. Discovery of a highly selective chemical inhibitor of matrix metalloproteinase-9 (MMP-9) that allosterically inhibits zymogen activation. J. Biol. Chem.292, 17963–17974 (2017).
- Pant, A. et al. Allosteric Site Inhibitor Disrupting Autoprocessing in Falcipains, Cysteine Proteases of Malaria Parasite. 205
- Pant, A. et al. Allosteric Site Inhibitor Disrupting Autoactivation of Cysteine Proteases of Plasmodium falciparum. Sci. Rep.8, 16193 (2018).
- Erickson, J. W. & Burt, S. K. Structural mechanisms of HIV drug resistance. Annu. Rev. Pharmacol. Toxicol. 36, 545–71 (1996).
- Kolli, M., Stawiski, E., Chappey, C. & Schiffer, C. a. Human immunodeficiency virus type 1 protease-correlated cleavage site mutations enhance inhibitor resistance. J. Virol. 83, 11027–42 (2009).
- Peterson, D. S., Milhous, W. K. & Wellems, T. E. Molecular basis of differential resistance to cycloguanil and pyrimethamine in Plasmodium falciparum malaria. Proc. Natl. Acad. Sci. U.S.A. 87, 3018–22 (1990).
- Peterson, D. S., Walliker, D. & Wellems, T. E. Evidence that a point mutation in dihydrofolate reductase-thymidylate synthase confers resistance to pyrimethamine in falciparum malaria. Proc. Natl. Acad. Sci. U.S.A. 85, 9114–8 (1988).