Structure based drug design of novel anti-fungal agents imported into cells by the integral membrane transporter, UapA

There is an urgent need for new anti-fungal agents. The focus of this project is, UapA, the uric-acid/xanthine transporter from Aspergillus nidulans. The normal function of UapA is to mediate uptake of purines but it also can transport the drug allopurinol. There is evidence to suggest that allopurinol is transported via a different mechanism to the native substrate. The aim is to obtain a structure of UapA in complex with allopurinol using approaches developed in the Byrne laboratory. The structure will provide a framework for structure based rational drug design based on allopurinol, using the expertise of the Fuchter group.

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