Identification of small molecule inhibitors targeting Plasmodium falciparum Hsp70-Hop pathway
type: CreativeWork
description: Malaria is caused by protozoan parasites of the Plasmodium genus. An estimated 405 000 million deaths due to malaria were reported in 2018. Plasmodium falciparum (P. falciparum) accounts for the deadliest form of the disease in Sub-Saharan Africa. P. falciparum has a complex life cycle spanning across both the mosquito vector and human hosts. During the lifecycle, the parasite is thus subjected to various physiological conditions. Therefore the parasite generally survives under stressful conditions and in response it upregulates its own molecular chaperones mainly the heat shock proteins (Hsps) in order to protect its protein constituents for survival. Heat shock protein 70 (Hsp70) together with heat shock protein 90 (Hsp90) are regarded as the most abundant cellular chaperones. Hsp70 and Hsp90 cooperate in order to exchange peptide substrates for folding and maturation. The cooperation of Hsp90 and Hsp70 is known to be facilitated by a co-chaperone, Hsp70-Hsp90 organizing protein (HOP) which serves as a module to facilitate interaction of the two chaperones. P. falciparum Hop (PfHop; PF3D7_1434300) brings together PfHsp70-1 and PfHsp90 into a functional complex. PfHop interacts with PfHsp70-1 (PF3D7_0818900) and PfHsp90 (PF3D7_0708400) through its tetracopeptide repeats (TPR) domains. PfHsp70-1 and PfHsp90 possess C-terminal EEVD and MEEVD motifs, respectively. The TPR1 and TPR2A of PfHop bind to the EEVD motif of PfHsp70-1 while TPR2B binds to the MEEVD motif of PfHsp90. It is thought that PfHsp70-1, PfHop and PfHsp90 form a functional complex that facilitates the folding of specific parasite proteins. Both PfHsp70-1 and PfHsp90 are essential molecules that could be specifically inhibited by potential antimalarial drugs. Therefore, this study evaluated the inhibition of the functional partnership between PfHop and PfHsp70-1 by colistin sulfate and pifithrin µ. In order to carry out in vitro assays, both PfHop and PfHsp70-1 were heterologously expressed in E. coli …
abstract: Malaria is caused by protozoan parasites of the Plasmodium genus. An estimated 405 000 million deaths due to malaria were reported in 2018. Plasmodium falciparum (P. falciparum) accounts for the deadliest form of the disease in Sub-Saharan Africa. P. falciparum has a complex life cycle spanning across both the mosquito vector and human hosts. During the lifecycle, the parasite is thus subjected to various physiological conditions. Therefore the parasite generally survives under stressful conditions and in response it upregulates its own molecular chaperones mainly the heat shock proteins (Hsps) in order to protect its protein constituents for survival. Heat shock protein 70 (Hsp70) together with heat shock protein 90 (Hsp90) are regarded as the most abundant cellular chaperones. Hsp70 and Hsp90 cooperate in order to exchange peptide substrates for folding and maturation. The cooperation of Hsp90 and Hsp70 is known to be facilitated by a co-chaperone, Hsp70-Hsp90 organizing protein (HOP) which serves as a module to facilitate interaction of the two chaperones. P. falciparum Hop (PfHop; PF3D7_1434300) brings together PfHsp70-1 and PfHsp90 into a functional complex. PfHop interacts with PfHsp70-1 (PF3D7_0818900) and PfHsp90 (PF3D7_0708400) through its tetracopeptide repeats (TPR) domains. PfHsp70-1 and PfHsp90 possess C-terminal EEVD and MEEVD motifs, respectively. The TPR1 and TPR2A of PfHop bind to the EEVD motif of PfHsp70-1 while TPR2B binds to the MEEVD motif of PfHsp90. It is thought that PfHsp70-1, PfHop and PfHsp90 form a functional complex that facilitates the folding of specific parasite proteins. Both PfHsp70-1 and PfHsp90 are essential molecules that could be specifically inhibited by potential antimalarial drugs. Therefore, this study evaluated the inhibition of the functional partnership between PfHop and PfHsp70-1 by colistin sulfate and pifithrin µ. In order to carry out in vitro assays, both PfHop and PfHsp70-1 were heterologously expressed in E. coli …
author: Muthelo, Tshifhiwa
language: en
keywords: Plasmodium falciparum, Molecular chaperone, PfHsp70-1, PfHop, Inhibitor, Colistin sulfate, Pifithrin
date published: 2020-06-26
date modified: 2026-07-27T21:57:42Z
provider: University of Venda
publisher: Networked Digital Library of Theses and Dissertations
type: WebPage
source organization: University of Venda

PropertyValue
property ID: Handle
value: http://hdl.handle.net/11602/1658