- Title
- Selective modulation of plasmodial Hsp70s by small molecules with antimalarial activity
- Creator
- Cockburn, Ingrid L, Boshoff, Aileen, Pesce, Eva-Rachele, Blatch, Gregory L
- Subject
- To be catalogued
- Date
- 2014
- Type
- text
- Type
- article
- Identifier
- http://hdl.handle.net/10962/431192
- Identifier
- vital:72752
- Identifier
- xlink:href="https://doi.org/10.1515/hsz-2014-0138"
- Description
- Plasmodial heat shock protein 70 (Hsp70) chaperones represent a promising new class of antimalarial drug targets because of the important roles they play in the survival and pathogenesis of the malaria parasite Plasmodium falciparum. This study assessed a set of small molecules (lapachol, bromo-β-lapachona and malonganenones A, B and C) as potential modulators of two biologically important plasmodial Hsp70s, the parasite-resident PfHsp70-1 and the exported PfHsp70-x. Compounds of interest were assessed for modulatory effects on the steady-state basal and heat shock protein 40 (Hsp40)-stimulated ATPase activities of PfHsp70-1, PfHsp70-x and human Hsp70, as well as on the protein aggregation suppression activity of PfHsp70-x. The antimalarial marine alkaloid malonganenone A was of particular interest, as it was found to have limited cytotoxicity to mammalian cell lines and exhibited the desired properties of an effective plasmodial Hsp70 modulator. This compound was found to inhibit plasmodial and not human Hsp70 ATPase activity (Hsp40-stimulated), and hindered the aggregation suppression activity of PfHsp70-x. Furthermore, malonganenone A was shown to disrupt the interaction between PfHsp70-x and Hsp40. This is the first report to show that PfHsp70-x has chaperone activity, is stimulated by Hsp40 and can be specifically modulated by small molecule compounds.
- Format
- computer, online resource, application/pdf, 1 online resource (9 pages), pdf
- Publisher
- De Gruyter
- Language
- English
- Relation
- Biological Chemistry, Cockburn, I.L., Boshoff, A., Pesce, E.R. and Blatch, G.L., 2014. Selective modulation of plasmodial Hsp70s by small molecules with antimalarial activity. Biological chemistry, 395(11), pp.1353-1362, Biological Chemistry volume 395 number 11 p. 1353 2014 1437-4315
- Rights
- Publisher
- Rights
- Use of this resource is governed by the terms and conditions of the De Gruyter General and License Terms and Conditions Statement (https://www.degruyter.com/publishing/services/rights-and-permissions/repositorypolicy)
- Rights
- Closed Access
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Collections
RU DST/NRF SARChI for Biotechnology Innovation and Engagement
Boshoff, Aileen (Assoc Prof)
Blatch, Gregory Lloyd (Prof)
RU Department of Biochemistry, Microbiology and Bioinformatics
SDG 03. Good Health and Well-Being
| Thumbnail | File | Description | Size | Format | |||
|---|---|---|---|---|---|---|---|
| View Details | SOURCE1 | Selective modulation of plasmodial Hsp70s by small molecules with antimalarial activity.pdf | 1 MB | Adobe Acrobat PDF | View Details |