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Dr. David M Wyatt
School of Biosciences
The University of Kent
Canterbury, Kent, CT2 7NJ,
Email: WyattD@cf.ac.uk
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Research
Many organisms encode diverse families of aspartic proteinases and often these enzymes play important roles in the pathogenesis of human and plant diseases. For example, the human malaria parasite P. falciparum encodes 10 enzymes known as plasmepsins, nine of which are aspartic proteinases. The remaining member of this family is a novel histoaspartic proteinase known as HAP. We are involved in the characterisation of these proteinases and other equivalent enzymes from rodent malaria models as they are good anti-malarial drug targets. We are particularly interested in the activity of HAP, as this enzyme potentially generates proteolytic activity using a serine proteinase-type mechanism, but within an aspartic proteinase topology. This indicates that aspartic proteinases have structural plasticity that potentially allows them to host different catalytic mechanisms. To study this, we are generating mutant forms of aspartic proteinases with altered catalytic properties and are using these mutant enzymes to elucidate the proteolytic mechanism of HAP.
We are also studying the interactions between aspartic proteinases and protein inhibitors. In particular, we are interested in the interactions between IA3, a 68 amino acid polypeptide and its target enzyme, proteinase A from S. cerevisae. IA3 is a potent and exquisitely specific inhibitor, which upon binding to its target proteinase undergoes a structural transition from an unstructured polypeptide, to an amphipathic alpha helix. We are investigating the potential of this unprecedented mode of inhibition to inactivate other aspartic proteinases that have medical and biotechnological significance.
Collaborations
Dr Mark Howard, The University of Kent,
Dr Richard Williamson, The University of Kent,
Professor John Kay, Cardiff University, UK.
Dr Colin Berry, Cardiff University, UK.
Professor Carlos Faro, University Coimbra, Portugal.
Publications





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