Research Interests   Structural enzymology: Metal ions & organic co-factors Human disease: Cardiovascular, Alzheimer's

Would you like to see biochemistry in motion? To learn exactly how enzymes accelerate and control chemistry at the molecular level? Then you might want to contact me.

My primary interest is to understand how protein enzymes containing catalytic metal ions and/or post-translational modifications can control chemistry of relevance to human health and disease. The principle tool of my research is macromolecular X-ray crystallography, in combination with spectroscopic techniques both in the crystal and solution, kinetics and mutagenesis. My most recent 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.

Post-translational modifications of protein amino acids, such as phosphorylation and glycosylation, are well known modulators of signaling pathways and recognition sites. In contrast, only recently has it been recognized that post-translational modifications in enzyme active sites can generate novel catalytic cofactors. In the last decade the number of these identified modifications has increased from just a handful to around 30, and continues to grow. Many of these enzymes are of biomedical importance, such as copper-containing amine oxidase, linked to congestive heart disease, vascular changes in late diabetic complications and inflammation. Understanding the role these cofactors play in catalysis, and additionally how they are synthesized, provides targets for drug discovery. Other examples have practical applications as biosensors, biocatalysts, and in bioremediation, such as methylamine dehydrogenase studied in my lab.

Proteins I study include methylamine dehydrogenase, copper-containing amine oxidase, cytochrome P460 (a potential drug target in Burkholdaria cepacia ; an important opportunistic pathogen of patients with cystic fibrosis), chlorite dismutase (a key enzyme in bacteria mediated chlorite breakdown in water treatment facilities) and soluble molecular assemblies linked to Alzheimer's disease.

(left to right); Ed Hoeffner, Brandon Goblirsch, Teresa De la Mora-Rey, Carrie Wilmot, Bryan Johnson, Val Klema

Recent Publications (2005-2007)

De la Mora-Rey, T. & Wilmot, C.M. Synergy within structural biology of single crystal optical spectroscopy and x-ray crystallography. Current Opinion in Structural Biology (2007) 17: 580-586. (Pubmed)

Pearson, A.R., Elmore, B.O., Yang, C., Ferrara, J.D., Hooper, A.B. & Wilmot, C.M. The crystal structure of cytochrome P460 of Nitrosomonas europea reveals a novel cytochrome fold and heme-protein cross-link. Biochemistry (2007) 46: 8340-8349. (ACS AuthorChoice Free Access) (Pubmed)

Johnson, B.J., Cohen, J., Welford, R.W., Pearson, A.R., Schulten, K., Klinman, J.P. & Wilmot, C.M. Exploring molecular oxygen pathways in Hansenula polymorpha copper-containing amine oxidase. J. Biological Chemistry (2007) 282: 17767-17776. (Pubmed)

Knowles, P., Kurtis, C., Murray, J., Saysell, C., Tambyrajah, W., Wilmot, C., McPherson, M.J., Phillips, S., Dooley, D., Brown, D., Rogers, M. & Mure, M. Hydrazine and amphetamine binding to amine oxidase: old drugs with new prospects. J. Neural Transmission (2007) 114: 743-746. (Pubmed)

Wilmot, C.M. An ancient and intimate partnership. Science (2007) 316: 379-380. (Free access at Science through this link) (Pubmed)

Wilmot, C.M. Fighting toxic copper in a bacterial pathogen. Nature Chemical Biology (2007) 3: 15-16. (Pubmed)

Pearson, A.R., Pahl, R., Kovaleva, E.G., Davidson, V.L. & Wilmot, C.M. Tracking X-ray-derived redox changes in crystals of a methylamine dehydrogenase/amicyanin complex using single-crystal UV/Vis micro-spectrophotometry. J. Synchrotron Radiation (2007) 14: 92-98. (Pubmed)

Li, X., Jones, L.H., Pearson, A.R., Wilmot, C.M. & Davidson, V.L. Mechanistic possibilities in MauG-dependent tryptophan tryptophylquinone biosynthesis. Biochemistry (2006) 45: 13276-13283. (Pubmed)

Pearson, A.R., Marimanikkuppam, S., Li, X., Davidson, V.L. & Wilmot, C.M. Isotope labelling studies reveal the order of oxygen incorporation into the tryptophan tryptophylquinone cofactor of methylamine dehydrogenase. J. Am. Chem. Soc. (2006) 128: 12416-12417. (Pubmed)

Elmore, B.O., Pearson, A.R., Wilmot, C.M. & Hooper A.B. Expression, purification, crystallization and preliminary X-ray diffraction of a novel Nitrosomonas europaea cytochrome, cytochrome P460. Acta Cryst. (2006) F62, 395-398. (Pubmed)

Wang, Y., Li, X., Jones, L.H., Pearson, A.R., Wilmot, C.M. & Davidson, V.L. MauG-dependent in vitro biosynthesis of tryptophan tryptophylquinone in methylamine dehydrogenase. J. Am. Chem. Soc. (2005) 127, 8258-8259. (Pubmed)

Jones, L.H., Pearson, A.R., Tang, Y., Wilmot, C.M. & Davidson, V.L. Active site aspartate residues are critical for tryptophan tryptophylquinone biogenesis in methylamine dehydrogenase. J. Biological Chemistry (2005) 280, 17392-17396. (Pubmed)

Mure, M., Brown, D.E., Saysell, C., Rogers, M.S., Wilmot, C.M., Kurtis, C.R., McPherson, M.J., Phillips, S.E.V., Knowles, P.F. & Dooley, D.M. Role of the interactions between the active site base and the substrate Schiff base in amine oxidase catalysis. Evidence from structural and spectroscopic studies of the 2-hydrazinopyridine adduct of Escherichia coli amine oxidase. Biochemistry (2005) 44, 1568-1582. (Pubmed)

Mure, M., Kurtis, C.R., Brown, D.E., Rogers, M.S., Tambyrajah, W.S., Saysell, C., Wilmot, C.M., Phillips, S.E.V., Knowles, P.F., Dooley, D.M. & McPherson, M.J. Active site rearrangement of the 2-hydrazinopyridine adduct in Escherichia coli amine oxidase to an azo copper(II) chelate form: A key role for tyrosine 369 in controlling the mobility of the TPQ-2HP adduct. Biochemistry (2005) 44, 1583-1594. (Pubmed)