Education & Background
Ph.D., Birkbeck College, University of London, 1989
Cancer Research Institute Postdoctoral Fellow, The Scripps Research Institute, 1989
Research Fellow, University of Leeds, UK, 1992
EMBO Postdoctoral Fellow, Uppsala University, Sweden, 1997
Would you like to see biochemistry in motion? To learn exactly how enzymes accelerate and control chemistry at the molecular level? My primary interest is to understand the mechanisms of post-translational modification required for protein enzyme activity. Post-translational modifications of proteins, such as phosphorylation and glycosylation, are well known modulators of signaling pathways and molecular/cellular recognition. Only in the last few decades has their wide-spread role in generating novel catalytic cofactors within enzyme active sites been appreciated.
The principle tool of my research is macromolecular X-ray crystallography in combination with spectroscopic techniques both in the crystal and solution, kinetics and mass spectrometry. My approach has been to freeze trap catalytic intermediates in the crystal, leading to "snapshots" along the reaction pathway. These are then assembled into a "movie of catalysis" at the molecular level.
Additionally my lab is also interested in the use of microbial enzymes in bioremediation (removal of pollutants from the environment using biological organisms) and biofuel production (microbial production of energy-rich hydrocarbons as replacement fuels).
Cheng Z, Cheung P, Kuo AJ, Yukl ET, Wilmot CM, Gozani O, Patel DJ. (2014) A molecular threading mechanism underlies Jumonji lysine demethylase KDM2A regulation of methylated H3K36. Genes Dev. 28(16):1758-71 (Pubmed)
Accompanying Perspective: Tsai, Shi & Tainer (2014) How substrate specificity is imposed on a histone demethylase−lessons from KDM2A. Genes & Development 28: 1735-38 (Pubmed)
Shin, S., Yukl, E.T., Sehanobish, E., Wilmot, C.M. & Davidson, V.L. (2014) Site-directed mutagenesis of Gln103 reveals the influence of this residue on the redox properties and stability of MauG. Biochemistry. 53(8):1342-9 (Pubmed)
Ou, L., Herzog, T.L., Wilmot, C.M. & Whitley, C.B. (2014) Standardization of α-L-iduronidase enzyme assay with Michaelis-Menten kinetics. Mol. Genet. Metab. 111: 113-115 (Pubmed)
Makris, T.M., Knoot, C.J., Wilmot, C.M. & Lipscomb, J.D. (2013) Structure of a dinuclear iron cluster-containing beta hydroxylase active in antibiotic biosynthesis. Biochemsitry 52: 6662-6671 (Pubmed)
Yukl, E.T., Williamson, H.R., Higgins, L., Davidson, V.L. & Wilmot, C.M. (2013) Oxidative damage in MauG: implications for control of high-valent iron species and radical propagation pathways. Biochemistry 52: 9447-9455 (Pubmed)
Tarboush, N.A., Yukl, E.T., Shin, S., Feng, M., Wilmot, C.M. & Davidson, V.L. (2013) The carboxyl group of Glu113 is required for stabilization of the diferrous and bis-FeIV states of MauG. Biochemistry 52: 6358-6367 (Pubmed)
Cedervall, P., Hooper, A.B. & Wilmot, C.M. (2013) Structural studies of hydroxylamine oxidoreductase reveal a unique heme cofactor and a previously unidentified interaction partner. Biochemistry 52: 6211-6218. (Pubmed)
DuBois, J.L., Carrell, C.J. & Wilmot, C.M. (2013). Reactivity and structure in the CDE protein superfamily: from O2 generation to peroxidase chemistry and beyond. In Handbook of Porphyrin Science, Ed. Ferreira, G., World Scientific, volume 26, chapter 127, 442-470.
Johnson, B.J., Yukl, E.T., Klema, V.J., Klinman, J.P. & Wilmot, C.M. (2013) Structural snapshots from the oxidative half-reaction of a copper amine oxidase: implications for O2 activation J. Biol. Chem. 288: 28409-28417. (Pubmed)
Yukl, E.T., Jensen, L.M.R., Davidson, V.L. & Wilmot, C.M. (2013) Structures of MauG in complex with quinol and quinone MADH. Acta Crystallographica Section F 69: 738-743. (Pubmed)
Davidson,V.L. & Wilmot, C.M. (2013) Posttranslational biosynthesis of the protein-derived cofactor tryptophan tryptophylquinone. Annu. Rev. Biochem. 82: 531-550. (Pubmed)
Tarboush, N.A., Jensen, L.M.R, Wilmot, C.M. & Davidson, V.L. (2013) A Trp199Glu MauG variant reveals a role for Trp199 interactions with pre-methylamine dehydrogenase during tryptophan tryptophylquinone biosynthesis.FEBS Lett. 587: 1736-1741. (Pubmed)
Yukl, E.T., Liu, F., Krzystek, J., Shin, S., Jensen, L.M.R., Davidson, V.L., Wilmot, C.M. & Liu, A. (2013) A di-radical intermediate within the context of tryptophan tryptophylquinone biosynthesis. Proc. Natl. Acad. Sci. USA. 110: 4569-4573. (Pubmed)
Klema, V.J., Solheid, C.J., Klinman, J.P. & Wilmot, C.M. (2013) Structural analysis of aliphatic vs. aromatic substrate specificity in a copper amine oxidase from Hansenula polymorpha. Biochemistry. 52: 2291-2301 (Pubmed)
Wilmot, C.M. & Yukl, E.T. MauG: a di-heme enzyme required for methylamine dehydrogenase maturation. Dalton Trans. (2013) 42: 3127-3135. (Pubmed)
Jensen, L.M., Meharenna, Y.T., Davidson, V.L., Poulos, T.L., Hedman, B., Wilmot, C.M. & Sarangi, R. Geometric and electronic structures of the His-Fe(IV)=O and His-Fe(IV)-Tyr hemes of MauG. J. Biol. Inorg. Chem. (2012) 17: 1241-1255 (Pubmed)
Wilmot, C.M. Polysaccharide monoxygenases: giving a boost to biofuel production. Structure (2012) 20: 938-940. (ScienceDirect)
Goblirsch, B.R., Frias, J.A., Wackett, L.P. & Wilmot, C.M. Crystal structures of Xanthomonas campestris OleA reveal features that promote head-to-head condensation of two long-chain fatty acids. Biochemistry (2012) 51: 4138-4146. (Pubmed)
Klema V.J. & Wilmot C.M. The role of protein crystallography in defining the mechanisms of biogenesis and catalysis in copper amine oxidase. Int. J. Mol. Sci. (2012) 13: 5375-5405. (open access)
Klema, V.J., Johnson, B.J., Klinman, J.P. & Wilmot, C.M. The precursor form of Hansenula polymorpha copper amine oxidase-1 in complex with Cu(I) and Co(II). Acta Cryst. F (2012) 68: 501-510. (PubMed)
Yukl, E.T. & Wilmot, C.M. In-situ creation of proteinaceous cofactors. Curr. Opin. Chem. Biol. (2012) 16: 54-59. (Pubmed)
Feng, M., Jensen, L.M.R, Yukl, E.T., Wei, X., Liu, A., Wilmot, C.M. & Davidson, V.L. Proline 107 is a major determinant in maintaining the structure of the distal pocket and reactivity of the high-spin heme of MauG. Biochemistry (2012) 51: 1598-1606. (Pubmed)