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Durham University

Department of Biosciences

Biomolecular Interactions

Bioscience Embedded within Chemistry.

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.

Group Coordinator: Dr Paul Denny

Academic Staff: Dr Tim R BlowerProf Martin CannDr Peter Chivers, Dr Paul Denny, Dr Karrera Djoko, Dr Sushma Grellschied, Dr Ehmke Pohl, Prof. Nigel RobinsonDr Martin Schröder, Dr Gary Sharples, Prof A Walmsley.

Affiliates: Dr Adam Benham, Dr P Chazot, Dr Tony Fawcett, Professor John A. Gatehouse, Dr Martin Goldberg, Prof Keith Lindsey, Dr J Liu, Dr David Weinkove

Recent Publications

  • A complex suite of loci and elements in eukaryotic type II topoisomerases determine selective sensitivity to distinct poisoning agents. Blower, T.R., Bandak, A., Lee, A.S.Y., Austin, C.A., Nitiss, J.L. & Berger, J.M. Nucleic Acids Research (2019). DOI: 10.1093/nar/gkz579
  • A unique dynamin-related protein is essential for mitochondrial fission in Toxoplasma gondii. Melatti C, Pieperhoff M, Lemgruber L, Pohl E, Sheiner L, Meissner M. PLOS Pathogens (2019) DOI: 10.1371/journal.ppat.1007512
  • A unique ferredoxin acts as a player in the low-iron response of photosynthetic organisms. Schorsch M, Kramer M, Goss T, Eisenhut M, Robinson N, Osman D, Wilde A, Sadaf S, Brückler H, Walder L, Scheibe R, Hase T, Hanke GT. Proceedings of the National Academy of Sciences of the United States of America. (2018) DOI 10.1073/pnas.1810379115
  • Bacterial sensors define intracellular free energies for correct enzyme metalation. Osman D, Martini MA, Foster AW, Chen J, Scott AJP, Morton RJ, Steed JW, Lurie-Luke E, Huggins TG, Lawrence AD, Deery E, Warren MJ, Chivers PT, Robinson NJ. Nature Chemical Biology. (2019) DOI: 10.1038/s41589-018-0211-4
  • Co(II) and Ni(II) binding of the Escherichia coli transcriptional repressor RcnR orders its N-terminus, alters helix dynamics, and reduces DNA affinity. Huang, H-T., Bobst, C. E., Iwig, J. S., Chivers, P. T., Kaltashov, I. & Maroney, M. J. Journal of Biological Chemistry (2018) DOI: 10.1074/jbc.RA117.000398
  • The intracellular immune receptor Rx1 regulates the DNA-binding activity of a Golden2-like transcription factor. Townsend PD, Dixon CH, Slootweg EJ, Sukarta OC, Yang AW, Hughes TR, Sharples GJ, Palsson LO, Takken FLW, Goverse A, Cann MJ. Journal of Biological Chemistry (2017) DOI:10.1074/jbc.RA117.000485
  • Fine control of metal concentrations is necessary for cells to discern zinc from cobalt. Osman, D., Foster, A.W., Chen, J., Svedaite, K., Steed, J.W., Lurie-Luke, E., Huggins, T.G., Robinson, N.J. (2017) Nature Communications, 8: 1884 (1-12). DOI:10.1038/s41467-017-02085-z
  • Functional and phylogenetic evidence of a bacterial origin for the first enzyme in sphingolipid biosynthesis in a phylum of eukaryotic protozoan parasites. Mina JG, Thye JK, Alqaisi AQI, Bird LE, Dods RH, Groftehauge MK, Mosely JA, Pratt S, Shams-Eldin H, Schwarz RT, Pohl E, Denny PW. Journal of Biological Chemistry. 2017 Jun 2. doi 10.1074/jbc.M117.792374
  • A tight tunable range for Ni(II) sensing and buffering in cells. Foster AW, Pernil R, Patterson CJ, Scott AJ, Pålsson LO, Pal R, Cummins I, Chivers PT, Pohl E, Robinson NJ. Nat Chem Biol. 2017 Feb 6. doi: 10.1038/nchembio.2310
  • Elucidation of the biosynthesis of the methane catalyst coenzyme F430. Moore SJ, Sowa ST, Schuchardt C, Deery E, Lawrence AD, Ramos JV, Billig S, Birkemeyer C, Chivers PT, Howard MJ, Rigby SE, Layer G, Warren MJ Nature. 2017 Feb 22. DOI:10.1038/nature21427
  • The mechanism of a formaldehyde-sensing transcriptional regulator. Denby KJ, Iwig J, Bisson C, Westwood J, Rolfe MD, Sedelnikova SE, Higgins K, Maroney MJ, Baker PJ, Chivers PT, Green J. Sci Rep. 2016 Dec 9;6:38879. DOI:10.1038/srep38879
  • The Effectors and Sensory Sites of Formaldehyde-Responsive Regulator FrmR and Metal-Sensing Variant Deenah Osman, Cecilia Piergentili, Junjun Chen, Lucy N Sayer, Isabel Usón, Thomas G Huggins,Nigel J Robinson, and Ehmke Pohl (2016) J. Biol. Chem. jbc.M116.745174. doi:10.1074/jbc.M116.745174
  • Mycobacterium tuberculosis RuvX is a Holliday junction resolvase formed by dimerisation of the monomeric YqgF nuclease domain. Nautiyal A, Rani PS, Sharples GJ, Muniyappa K. Mol Microbiol. 2016 Jan 28. doi: 10.1111/mmi.13338.
  • Crystal structure and stability of gyrase–fluoroquinolone cleaved complexes from Mycobacterium tuberculosis Tim R. Blower, Benjamin H. Williamson, Robert J. Kerns and James M. Berger PNAS 2016 ; vol. 113 no. 7, 1706-1713, doi:10.1073/pnas.1525047113
  • Fluoroquinolone interactions with Mycobacterium tuberculosis gyrase: Enhancing drug activity against wild-type and resistant gyrase Katie J. Aldred, Tim R. Blower, Robert J. Kerns, James M. Berger and Neil Osheroff PNAS 2016 ; vol. 113 no. 7, E839-E846 doi:10.1073/pnas.1525055113
  • The Tomato Nucleotide-Binding Leucine-Rich Repeat (NLR) Immune Receptor I-2 Couples DNA-Binding to Nucleotide-Binding Domain Nucleotide Exchange. Fenyk S, Dixon CH, Gittens WH, Townsend PD, Sharples GJ, Pålsson LO, Takken FL, Cann MJ. J. Biol. Chem. 2016 291: 1137-. , doi:10.1074/jbc.M115.698589
  • The Potato Nucleotide-Binding Leucine-Rich Repeat (NLR) Immune Receptor Rx1 is a Pathogen Dependent DNA-Deforming Protein - Fenyk, Stepan Townsend, Philip D. Dixon, Christopher H. Spies, Gerhard B. de San Eustaquio Campillo, Alba Slootweg, Erik J. Westerhof, Lotte B. Gawehns, Fleur K.K. Knight, Marc R. Sharples, Gary J. Goverse, Aska Pålsson, Lars-Olof Takken, Frank L.W., Cann, Martin J. J. Biol. Chem. 2015 290: 24945-24960. doi:10.1074/jbc.M115.672121
  • The role of protein-ligand contacts in allosteric regulation of the Escherichia coli Catabolite Activator Protein - Townsend, P.D. Rodgers, T.L. Glover, L.C. Korhonen, H.J. Richards, S.A. Colwell, L.J. Pohl, E. Wilson, M.R. Hodgson, D.R.W. McLeish, T.C.B. Cann, M.J. J. Biol. Chem. 2015 290: 22225-22235. doi:10.1074/jbc.M115.669267
  • Generating a metal-responsive transcriptional regulator to test what confers metal-sensing in cells. - Osman, D. Piergentili, C. Chen, J. Chakrabarti, B. Foster, A. Lurie-Luke, E. Huggins, T. Robinson, N. J. Biol. Chem. 2015 290: 19806-19822. doi:10.1074/jbc.M115.663427
  • Metal preferences and metallation. Foster AW, Osman D, Robinson NJ. J. Biol. Chem. 2014 289: 28095-28103. doi:10.1074/jbc.R114.588145
  • A chemical potentiator of copper-accumulation used to investigate the iron-regulons of Saccharomyces cerevisiae. Foster AW, Dainty SJ, Patterson CJ, Pohl E, Blackburn H, Wilson C, Hess CR, Rutherford JC, Quaranta L, Corran A, Robinson NJ. Molecular Microbiology. 93(2):317-330, July 2014. doi: 10.1111/mmi.12661.
  • Metal specificity of cyanobacterial nickel-responsive repressor InrS: cells maintain zinc and copper below the detection threshold for InrS. Foster AW, Pernil R, Patterson CJ, Robinson NJ. Molecular Microbiology. 92(4):797-812, May 2014 doi: 10.1111/mmi.12594

The Metals in Biology BBSRC Network in Industrial Biotechnology and Bioenergy emerged from this research group in 2014

Insight into the effect of antibiotics on tuberculosis

Researchers studying the activity of antibiotics against tuberculosis have visualised the drugs in action, leading to new ideas of how to protect against increasing antibiotic resistance.