Biomolecular Interactions

Bioscience Embedded within Chemistry - Group Coordinator: Professor Tim Blower

Biomolecular interactions, including contacts between biological macromolecules (protein/protein or protein/nucleic acids) and protein-ligand interactions are central to biochemistry. This grouping addresses fundamental questions concerning, for example, the recognition of DNA by bacterial proteins, the biophysical basis of allostery and the supply of metals to proteins. Multiple projects aim to identify targets for new antimicrobial (and antiviral) compounds and typically exploit a wide range of chemical, biochemical, and biophysical methods.

More than half of the members of the group are located in embedded biology laboratories within the Department of Chemistry and PIs have close interactions with the Bioactive Chemistry and Synthesis grouping in Chemistry.

Affiliated Members:

Dr Adam Benham, Dr P Chazot, Prof Tony Fawcett, Dr Martin Goldberg, Prof Keith Lindsey, Dr J Liu, Dr David Weinkove

Recent Publications

Petit, Guillaume A. and Hong, Yaoqin and Djoko, Karrera Y. and Whitten, Andrew E. and Furlong, Emily J. and McCoy, Airlie J. and Gulbis, Jacqueline M. and Totsika, Makrina and Martin, Jennifer L. and Halili, Maria A. (2022) The suppressor of copper sensitivity protein C from Caulobacter crescentus is a trimeric disulfide isomerase that binds copper(I) with subpicomolar affinity. Acta Crystallographica Section D Structural Biology

O’Hern, Charlotte I. Z. and Djoko, Karrera Y. (2022) Copper Cytotoxicity: Cellular Casualties of Noncognate Coordination Chemistry. mBio
 
Brouwer, Stephan and Jespersen, Magnus G. and Ong, Cheryl-lynn Y. and De Oliveira, David M. P. and Keller, Bernhard and Cork, Amanda J. and Djoko, Karrera Y. and Davies, Mark R. and Walker, Mark J. (2022) 'Streptococcus pyogenes Hijacks Host Glutathione for Growth and Innate Immune Evasion.  mBio

Djoko, Karrera and Cavet, Jennifer (2022) Perspectives on Metals in Microbiology Perspectives on Metals in Microbiology, Microbiology

Guillen-Garcia, A. and Gibson, S. and Jordan, C. and Ramaswamy, V. and Linthwaite, V. and Hodgson, D. and Blower, T. and Verlet, J. and Degiacomi, M. and Palsson, L-O. and Cann, M.J. (2022) Allophycocyanin A is a carbon dioxide receptor in the cyanobacterial phycobilisome. Nature Communications

Alpizer-Sosa, E.A., Ithnin, N.R.B., Pountain, A.W., Weidt, A.K., Donachie, A.M., Ritchie, R., Dickie, E.A., Burchmore, R.J.S., Denny, P.W., Barrett, M.P. (2022). Amphotericin B resistance in Leishmania mexicana: Alterations to sterol metabolism and oxidative stress response. PLOS Neglected Tropical Disease

Alpizar-Sosa, E.A., Kumordzi, Y., Wei, W., Whitfield, P., Barrett, M.P., Denny, P.W. (2022). Genome deletions to overcome the directed loss of gene function in Leishmania. Frontiers in Cellular and Infection Microbiology. 

Katy A S Cornish, Joanna Lange, Arnthór Aevarsson, Ehmke Pohl (2022). CPR-C4 is a highly conserved novel protease from the Candidate Phyla Radiation with remote structural homology to human vasohibins. Journal of Biological Chemistry

David M Picton, Joshua D Harling-Lee, Samuel J Duffner, Sam C Went, Richard D Morgan, Jay C D Hinton, Tim R Blower (2022). A widespread family of WYL-domain transcriptional regulators co-localizes with diverse phage defence systems and islands. Nucleic Acids Research Volume 50, Issue 9, 20 May 2022, Pages 5191–5207

Elise M.Ling, Arnaud Baslé, Ian G.Cowell, Bertvan den Berg, Tim R.Blower, Caroline A.Austin. (2022). A comprehensive structural analysis of the ATPase domain of human DNA topoisomerase II beta bound to AMPPNP, ADP, and the bisdioxopiperazine, ICRF193. Structure

Izaak N. Beck, David M.Picton, Tim R.Blower (2022). Crystal structure of the BREX phage defence protein BrxA. Current Research in Structural Biology, Volume 4.

Douglas O Escrivani, Rebecca L Charlton, Marjolly B Caruso, Gabriela A Burle-Caldas, Maria Paula G Borsodi, Russolina B Zingali, Natalia Arruda-Costa, Marcos V Palmeira-Mello, Jéssica B de Jesus, Alessandra M T Souza, Bárbara Abrahim-Vieira, Stefanie Freitag-Pohl, Ehmke Pohl, Paul W Denny, Bartira Rossi-Bergmann, Patrick G Steel (2021). Chalcones identify cTXNPx as a potential antileishmanial drug target. PLOS Negelcted Tropical Diseases.

Picton, D.M., Luyten, Y.A., Morgan, R.D., Nelson, A., Smith, D.L., Dryden, D.T.F., Hinton, J.C.D. & Blower, T.R. (2021). The phage defence island of a multidrug resistant plasmid uses both BREX and type IV restriction for complementary protection from viruses. Nucleic Acids Research

Linthwaite, V.L. and Pawloski, W. and Pegg, H.B. and Townsend, P.D. and Thomas, M.J. and Brown, A.P. and Hodgson, D.R.W. and Lorimer, G.H. and Fushman, D. and Cann, M.J. (2021) Ubiquitin is a carbon dioxide-binding protein., Science advances., 7 . eabi5507.

Usher, B. and Birkholz, N. and Beck, I.N. and Fagerlund, R.D. and Jackson, S.A. and Fineran, P.C. and Blower, T.R. (2021) Crystal structure of the anti-CRISPR repressor Aca2., Journal of Structural Biology, 213 (3). p. 107752.

Nijjar, Sarbjit and Maddison, Daniel and Meigh, Louise and Wolf, Elizabeth and Rodgers, Thomas and Cann, Martin and Dale, Nicholas (2021) Opposing modulation of Cx26 gap junctions and hemichannels by CO2., Journal of physiology, 599 (1). pp. 103-118.

Mina, John G. M., Charlton, Rebecca L., Alpizar-Sosa, Edubiel, Escrivani, Douglas O., Brown, Christopher, Alqaisi, Amjed, Borsodi, Maria Paula G., Figueiredo, Claudia P., de Lima, Emanuelle V., Dickie, Emily A., Wei, Wenbin, Coutinho-Silva, Robson, Merritt, Andy, Smith, Terry K., Barrett, Michael P., Rossi-Bergmann, Bartira, Denny, Paul W. & Steel, Patrick G. (2021). Antileishmanial Chemotherapy through Clemastine Fumarate Mediated Inhibition of the Leishmania Inositol Phosphorylceramide Synthase. ACS Infectious Diseases 7(1): 47-63

Tomlinson, Charles W. E., Cornish, Katy A. S., Whiting, Andrew & Pohl, Ehmke (2021). Structure-functional relationship of cellular retinoic acid binding proteins I and II interacting with natural and synthetic ligands. Acta Crystallographica Section D 77(2): 164-175.

Young, T.R., Martini, M.A., Foster, A.W., Glasfeld, A., Osman, D., Morton, R.J., Deery, E., Warren, M.J., Robinson, N.J. (2021) Calculating metalation in cells reveals CobW acquires Co^II for vitamin B₁₂ biosynthesis while related proteins prefer Zn^II. Nature Communications, 12: 1195 (1-15).

Cai, Y., Usher, B., Gutierrez, C., Tolcan, A., Mansour, M., Fineran, P.C., Condon, C., Neyrolles, O., Genevaux, P. & Blower, T.R. (2020). A nucleotidyltransferase toxin inhibits growth of Mycobacterium tuberculosis through inactivation of tRNA acceptor stems. Science Advances 6(31): eabb6651.

Stewart, Louisa J., Ong, Cheryl-lynn Y., Zhang, May M., Brouwer, Stephan, McIntyre, Liam, Davies, Mark R., Walker, Mark J., McEwan, Alastair G., Waldron, Kevin J. & Djoko, Karrera Y. (2020). Role of Glutathione in Buffering Excess Intracellular Copper in Streptococcus pyogenes. mBio 11(6): e02804-20.

Brown, Max, Dainty, Samantha, Strudwick, Natalie, Mihai, Adina D., Watson, Jamie N., Dendooven, Robina, Paton, Adrienne W., Paton, James C. & Schröder, Martin (2020). Endoplasmic reticulum stress causes insulin resistance by inhibiting delivery of newly synthesised insulin receptors to the cell surface. Molecular Biology of the Cell 31(23): 2495-2629.

Sharples, Gary J., Heddle, Jonathan G., Kozak, Maciej, Taube, Michał, Hughes, Timothy R, Pålsson, Lars-Olof, Bowers, Laura Y., Curtis, Fiona A., Plewka, Jacek, Świątek, Sylwia, Paterson, Joy R., Jolma, Arttu, Yang, Ally W.H., Gittens, William H., Trotter, Alexander J., Balakrishnan, Dhanasekaran & Chakraborti, Soumyananda (2020). A bacteriophage mimic of the bacterial nucleoid-associated protein Fis. Biochemical Journal 477(7): 1345-1362

Blower, T.R., Bandak, A., Lee, A.S.Y., Austin, C.A., Nitiss, J.L. & Berger, J.M. (2019). A complex suite of loci and elements in eukaryotic type II topoisomerases determine selective sensitivity to distinct poisoning agents. Nucleic Acids Research 47(15): 8163-8179.

Osman, D., Martini, M., Foster, A.W., Chen, J., Scott, A.J.P., Morton, R.J., Steed, J.W., Lurie-Luke, E., Huggins, T.G., Lawrence, A.D., Deery, E., Warren, M.J., Chivers, P.T., Robinson, N.J. (2019) Bacterial sensors define intracellular free energies for correct enzyme metalation. Nature Chemical Biology, 15: 241–249.

Linthwaite, V.L. and Janus, J.M. and Brown, A.P. and Wong-Pascua, D. and O’Donoghue, A.C. and Porter, A. and Treumann, A. and Hodgson, D.R.W. and Cann, M.J. (2018) The identification of carbon dioxide mediated protein post-translational modifications., Nature communications., 9 . p. 3092.

Townsend, P.D. and Dixon, C.H. and Slootweg, E.S. and Sukarta, O.C.A. and Yang, A.W.H. and Hughes, T.R. and Sharples, G.J. and Palsson, L-O. and Takken, F.L.W. and Goverse, A. and Cann, M.J. (2018) The intracellular immune receptor Rx1 regulates the DNA-binding activity of a Golden2-like transcription factor., Journal of biological chemistry., 293 (9). pp. 3218-3233.

Moore, S. and Sowa, S. and Schuchardt, C. and Deery, E. and Lawrence, A. and Ramos, J. and Billig, S. and Birkemeyer, C. and Chivers, P. and Howard, J. and Rigby, S. and Layer, G. and Warren, M. (2017) Elucidation of the biosynthesis of the methane catalyst coenzyme F430., Nature., 543 (7643). pp. 78-82.

Marsh, James W., Djoko, Karrera Y., McEwan, Alastair G. & Huston, Wilhelmina M. (2017). Copper(II)-bis(thiosemicarbazonato) complexes as anti-chlamydial agents. Pathogens and Disease 75(7): ftx084.