Structure-based Drug Discovery (SBDD)
Miss Nokwanda Mpontshane (MSc student) during her research visit to the Protein Crystallography Small Research Facility, Centre for Medicine Discovery, University of Oxford.
The research group employs a structure-based drug discovery (SBDD) approach to identify and optimise novel compounds targeting key enzymes in the ergosterol biosynthesis pathway of priority fungal pathogens.
The research integrates heterologous protein expression, purification, and X-ray crystallography to determine high-resolution structures of target enzymes. Using X-ray crystallographic fragment screening, small molecular fragments will be identified and optimised based on their binding interactions with target proteins. Structure-guided design will then inform the synthesis of improved compounds with enhanced affinity and specificity. Subsequent biochemical assays will evaluate compound potency and guide the selection of promising candidates for antifungal activity testing. This integrated structural and biochemical strategy aims to deliver new lead compounds for the development of effective antifungal therapeutics.
The research is conducted in collaboration with the Protein Crystallography Small Research Facility (PX-SRF) at the Centre for Medicines Discovery, University of Oxford, UK.
Model of 24C-sterol methyltransferase from Candida albicans bound to zymosterol – one of the protein targets for developing novel antifungals.
Conversion of zymosterol or lanosterol to fecosterol or eburicol by 24C-sterol methyltransferase in the ergosterol biosynthesis pathway of fungi.