Malaria Heat Shock Proteins: Drug Targets that Chaperone other Drug Targets

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Pesce, Eva-Rachele, Cockburn, J, Goble, L, Stephens, G and Blatch, Gregory ORCID: 0000-0003-0778-8577 (2010) Malaria Heat Shock Proteins: Drug Targets that Chaperone other Drug Targets. Infectious Disorders - Drug Targets , 10 (3). pp. 147-157. ISSN 1871-5265 (print) 2212-3989 (online)


Ongoing research into the chaperone systems of malaria parasites, and particularly of Plasmodium falciparum, suggests that heat shock proteins (Hsps) could potentially be an excellent class of drug targets. The P. falciparum genome encodes a vast range and large number of chaperones, including 43 Hsp40, six Hsp70, and three Hsp90 proteins (PfHsp40s, PfHsp70s and PfHsp90s), which are involved in a number of fundamental cellular processes including protein folding and assembly, protein translocation, signal transduction and the cellular stress response. Despite the fact that Hsps are relatively conserved across different species, PfHsps do exhibit a considerable number of unique structural and functional features. One PfHsp90 is thought to be sufficiently different to human Hsp90 to allow for selective targeting. PfHsp70s could potentially be used as drug targets in two ways: either by the specific inhibition of Hsp70s by small molecule modulators, as well as disruption of the interactions between Hsp70s and co-chaperones such as the Hsp70/Hsp90 organising protein (Hop) and Hsp40s. Of the many PfHsp40s present in the parasite, there are certain unique or essential members which are considered to have good potential as drug targets. This review critically evaluates the potential of Hsps as malaria drug targets, as well as the use of chaperones as aids in the heterologous expression of other potential malarial drug targets.

Item type Article
Subjects Historical > Faculty/School/Research Centre/Department > School of Biomedical and Health Sciences
Historical > FOR Classification > 1101 Medical Biochemistry and Metabolomics
Keywords ResPubID22186, plasmodium falciparum, molecular chaperones, heat shock proteins, Hsp40, Hsp70, Hsp90, heterologous protein expression
Citations in Scopus 62 - View on Scopus
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