Last Updated: 25/11/2025
A structure/function study of the P. falciparum calcium-dependent protein kinase family, a target for anti-malaria drug design
Objectives
This project aims to:
- Characterise the ATP binding sites of members of the CDPK family to identify unique and shared properties;
- Employ biochemical and biophysical approaches to characterise CDPK5 as an exemplar of the CDPK family;
- Identify proteins that interact with CDPK5 to elaborate on its biological function during parasite blood stage asexual division;
- Determine structures for the CDPK5 kinase and regulatory domains, as well as complexes of CDPK5 with inhibitors and binding partners;
- Carry out virtual screening to refine our understanding of CDPK-inhibitor recognition properties.
For control of malaria in developing countries, drug combinations will be necessary, ideally attacking distinct parasite-specific biochemical processes. Dysregulation of protein phosphorylation in human cells plays a major role in many diseases, and a number of protein kinase inhibitors are in the clinic. The P. falciparum calcium-dependent protein kinase (CDPK) family represents a validated target for drug design because members have essential roles in regulating the parasite life cycle in both hosts, and by sequence analysis, they have no homologues in the human kinome. To exploit the CDPK family for drug design, a greater understanding of their biochemical activity and regulation, and structural elaboration at atomic resolution is required.
Sep 2009 — Aug 2012
$306,975
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