Jessica Boakes

CASE – Structural characterisation of the equilibrative nucleoside transporter, a cancer drug target

My project

Integral membrane proteins, comprising about 30% of the human proteome, are very important targets for drug discovery efforts. Despite this, we currently have very little structural information about them: only approximately 2% of current protein structures belong to novel membrane protein families, and even fewer are human proteins.
Human equilibrative nucleoside transporter isoform-1 (hENT1) is involved in the uptake of nucleosides into cells, primarily to salvage DNA synthesis intermediates. However, it also directly influences the concentration of adenosine at the cell surface, and so affects e.g. coronary blood flow, inflammation and neurotransmission. Furthermore, hENT1 transports compounds like Cytarabine, Gemcitabine and other DNA replication terminating nucleoside analogues used in the treatment of cancers like non-Hodgins lymphoma and viral diseases including AIDS. Designing molecules to block the activity of hENT1 will be important for combating cytotoxic resistant cancer cells.
In this studentship, we will gain structural and functional information about hENT1 as the basis for structure-based drug design to produce novel anti-cancer drugs. We have already made significant progress toward the recombinant expression of hENT1 in insect cells (Sf9) transfected with baculovirus, and preliminary solubilisation and purification of hENT1 has demonstrated that structural studies will be feasible.


Not yet available.