MEMBRANE PROTEIN CRYSTALLOGRAPHY
Membrane proteins represent around 30% of the proteomes of most organisms and more than 40% of drug targets and yet few structures of these molecules have been solved by x-ray crystallography. Drug resistance of bacterial pathogens is a rising crisis. Bacterial membrane proteins are essential for resistance since they are involved in the export of the drugs from the cell. My group is interested in the structural and functional characterisation of multidrug membrane transporters by X-ray crystallography.
The lab is based at the Research Complex at Harwell, Oxfordshire (https://www.rc-harwell.ac.uk/research-groups/beis-group/).
We are also interested to exploit novel antibacterials as treatments for bacterial infections by understanding how bacteria secrete antibacterial peptides and hijack membrane transporters of other bacteria to inhibit their growth under nutrient starvation.
We are also interested to understand how ABC transporters recognise their substrates as well as the conformational changes associated with ATP and substrate binding, as well as ATP hydrolysis. We employ protein crystallography, transport assays and biophysical methods such as PELDOR/EPR and smFRET.
et al., 2020, Experimental phasing with vanadium and application to nucleotide-binding membrane proteins, Iucrj, Vol:7, ISSN:2052-2525, Pages:1092-1101
et al., 2020, Structural and functional diversity calls for a new classification of ABC transporters, Febs Letters, Vol:594, ISSN:0014-5793, Pages:3767-3775
Smits SHJ, Schmitt L, Beis K, 2020, Self-immunity to antibacterial peptides by ABC transporters, Febs Letters, Vol:594, ISSN:0014-5793, Pages:3920-3942
et al., 2019, Desolvation of the substrate binding protein TauA dictates ligand specificity for the alkanesulfonate ABC importer TauABC, Biochemical Journal, Vol:476, ISSN:0264-6021, Pages:3649-3660