Professor Anthony J Wilkinson
01904 328261
Email: tony.wilkinson@york.ac.uk
Structural analysis of proteins involved in cell fate and disease processes
Research Summary
Professor Wilkinson’s group uses structural biology as a key tool to dissect structure and mechanism in proteins. On the one hand, we have specific interests in proteins that contribute to disease and represent drug targets in pathogens in humans. On the other hand, we study systems of proteins that determine cellular fate during spore formation in Bacillus subtilis.
Current projects include:
- Targeting enzymes/proteins as targets for drug development to treat leishmaniasis
- Structural studies of proteins involved in cell fate determination in Bacillus subtilis and Clostridium difficile
Selected Publications
Holman, N.D.M., Wilkinson, A.J. & Smith, M.C.M. Alanine-scanning mutagenesis of protein mannosyl-transferase from Streptomyces coelicolor reveals strong activity-stability correlation. Microbiology doi: 10.1099/mic.0.001103. (2021)
Brannigan, J. A. & Wilkinson, A. J. Drug Discovery in Leishmaniasis using Protein Lipidation as a Target. Biophysical Reviews 13, 1139-1146 doi 10.1007/s12551-021-00855-0. (2021).
Leishmania differentiation requires ubiquitin conjugation mediated by a UBC2-UEV1 E2 complex.
Burge, RJ, Damianou, A, Wilkinson, A., Rodenko, B, & Mottram, JC. PLOS Pathogens 16, 10, 30 p., e1008784 (2020).The molecular basis of thioalcohol production in human body odour.
Rudden, M, Herman, R, Rose, M, Bawdon, D, Cox, DS, Dodson, E, Holden, MTG, Wilkinson, AJ, James, AG, Thomas, GH. Sci Rep. 10, doi: 10.1038/s41598-020-68860-z. (2020).Fragment-derived inhibitors of human N-myristoyltransferase block virus capsid assembly and replication of the common cold virus.
Mousnier, A, Bell, AS, Swieboda, DP, Morales-Sanfrutos, J, Pérez-Dorado, I, Brannigan, JA, Newman, J, Ritzefeld, M, Hutton, JA, Guedán, A, Asfor, AA, Robinson, SW, Hopkins-Navratilova, I, Wilkinson, AJ, Johnston, SL, Leatherbarrow, RJ, Tuthill, TJ, Solari, R & Tate, EW. Nature Chemistry 10, 599-606 (2018)A widespread family of serine/threonine protein phosphatases shares a common regulatory switch with proteasomal proteases
Bradshaw, N, Levdikov, VM, Zimanyi, CM, Gaudet, R, Wilkinson, AJ and Losick, R. eLife doi: 10.7554/eLife.26111. (2017).Structure of the Branched Chain Amino Acid and GTP Sensing Global Regulator, CodY, from Bacillus subtilis.
Levdikov VM, Blagova EV, Young VL, Belitsky BR, Lebedev A, Sonenshein AL, Wilkinson AJ. J. Biol. Chem. 292, 2714-2728 (2017).Tetramerization and interdomain flexibility of the replication initiation controller YabA enables simultaneous binding to multiple partners.
Felicori L, Jameson KH, Roblin P, Fogg MJ, Garcia-Garcia T, Ventroux M, Cherrier MV, Bazin A, Noirot P, Wilkinson AJ, Molina F, Terradot L, Noirot-Gros MF. Nucleic Acids Res. 44, 449-463 (2016).Validation of N-myristoyltransferase as an antimalarial drug target using an integrated chemical biology approach.
Wright MH, Clough B, Rackham MD, Rangachari K, Brannigan, JA, Grainger M, Moss DK, Bottrill AR, Heal WP, Broncel M, Serwa RA, Brady D, Mann DJ, Leatherbarrow RJ, Tewari R, Wilkinson AJ, Holder AH, & Tate EW. Nature Chemistry 6, 112-121 (2014).Structure of Components of an Intercellular Channel Complex in Sporulating Bacillus subtilis.
Levdikov, VM, Blagova, EV, McFeat, A, Fogg, MJ, Wilson, KS and Wilkinson, AJ. Proc. Natl. Acad. Sci. USA 109, 5441-5445 (2012).
Biographical summary
Tony Wilkinson trained for his PhD with Alan Fersht at Imperial College London working in protein engineering on tyrosyl tRNA synthetase. He joined the laboratory of James Wang at Harvard University working on DNA toposisomerases and subsequently the lab of Guy Dodson at the University of York learning protein crystallography working on ligand discrimination in oxygen transport proteins in a fruitful collaboration with John Olson at Rice University in Houston.
He subsequently took up an academic post in the York Structural Biology Laboratory in the Chemistry Department where he is now a Professor. His group has studied sequence-independent peptide binding in transporter systems and transcriptional regulators in Bacillus with a focus on the control and execution of the process of cell development leading to the formation of dormant spores. More recently he has been working on proteins from the pathogens Plasmodium falciparum that causes malaria, Leishmania donovani that causes leishmaniasis with a current focus on enzymes of post-translational modification systems which constitute potential drug targets.
