Professor Anthony J Wilkinson

01904 328261

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 study systems of proteins that determine cellular fate during spore formation in Bacillus subtilis. On the other hand, we have specific interests in proteins that contribute to virulence and represent drug targets in pathogens in humans and in livestock. 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
  • Structural studies of the virulence-associated proteins of the horse pathogen Rhodococcus equi

Selected Publications

Fragment-derived inhibitors of human N-myristoyltransferase block virus capsid assembly and replication of the common cold virus.
Mousnier, A. et al., Nature Chemistry, 10, 599-606 (2018).

A widespread family of serine/threonine protein phosphatases shares a common regulatory switch with proteasomal proteases.
Bradshaw, N., et al.,  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, et al., 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, et al., Nucleic Acids Res., 44, 449-463 (2016).

Structural characterisation of the virulence-associated protein VapG from the horse pathogen Rhodococcus equi.
Okoko T, et al., Vet Microbiol., 179, 42-52 (2015).

Validation of N-myristoyltransferase as an antimalarial drug target using an integrated chemical biology approach.
Wright MH, et al., Nature Chemistry, 6, 112-121 (2014).

Diverse modes of binding in structures of Leishmania major N-myristoyltransferase with selective inhibitors.
Brannigan JA, et al., IUCr J. 1, 250-260 (2014).

Global profiling of co- and post-translationally N-myristoylated proteomes in human cells.
Thinon E, et al., Nature Commun. 5: 4919. doi: 10.1038/ncomms5919 (2014).

Structure of Components of an Intercellular Channel Complex in Sporulating Bacillus subtilis.
Levdikov, VM, et al., 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. 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 that causes malaria, Leishmania donovani that causes leishmaniasis and Rhodococcus equi that causes lung disease in young horses.