6-155 Jackson Hall
321 Church Street SE
Minneapolis, MN 55455
United States
Carrie
Wilmot
I determine at the atomic level how enzyme cofactors are synthesized and used. I use X-ray crystallography, spectroscopy, mass spectrometry and freeze-trapping to define these processes both in solution and in crystals of the enzymes.
Research interests
Would you like to see biochemistry in motion? To learn exactly how enzymes accelerate and control chemistry at the molecular level? My lab is interested in bacterial natural product biosynthesis from peptides or activated fatty acids. The natural products we currently study range from enzyme cofactors (pyrroloquinoline quinone, PQQ), β-lactone containing molecules of therapeutic value (e.g. lipstatin), and long-chain hydrocarbons.
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.
Selected publications
Recent Publications
- Koehn, E.M., Latham, J.A., Armand, T., Evans III, R.L., Tu, X., Wilmot, C.M., Iavarone, A.T., Klinman, J.P. (2019) Discovery of hydroxylase activity for PqqB that provides a missing link in the pyrroloquinoline quinone biosynthetic pathway. J. Am. Chem. Soc. 141: 4398-4405.
- Jensen, M.R., Goblirsch, B.R., Esler, M.A., Christenson, J.K., Mohamed, F.A., Wackett, L.P., Wilmot, C.M. (2018) The role of OleA His285 in orchestration of long-chain acyl-coenzyme A substrates. FEBS Lett. 592: 987-998.
- Barr, I., Stich, T.A., Gizzi, A., Grove, T., Bonanno, J.B., Latham, J.A., Chung, T., Wilmot, C.M., Britt, R.D., Almo, S.C., Klinman, J.P. (2018) X-ray and EPR characterization of the auxiliary Fe-S clusters in the radical SAM enzyme PqqE. Biochemistry 57: 1306-1315.
- Jensen, M.R., Goblirsch, B.R., Christenson, J.K., Esler, M.A., Mohamed, F.A., Wackett, L.P., Wilmot, C.M. (2017) OleA Glu117 is key to condensation of two fatty-acyl coenzyme A substrates in long-chain olefin biosynthesis. Biochem. J. 474: 3871-3886.
- Tu, X., Latham, J.A., Klema, V.J., Evans III, R.L., Li, C., Klinman, J.P., Wilmot, C.M. (2017) Crystal structures reveal metal binding plasticity at the metallo-β-lactamase active site of PqqB from Pseudomonas putida. J. Biol. Inorg. Chem. 22: 1089-1097.
- Evans III, R.L., Latham, J.A., Xia, Y., Klinman, J.P., Wilmot, C.M. (2017) NMR structure and binding studies of PqqD, a chaperone required in the biosynthesis of the bacterial dehydrogenase cofactor pyrroloquinoline quinone. Biochemistry 56: 2735-2746.
- Christenson, J.K., Jensen, M.R., Goblirsch, B.R., Mohamed, F., Zhang, W., Wilmot, C.M., Wackett, L.P. (2017) Active multi-enzyme assemblies for long-chain olefinic hydrocarbon biosynthesis. J. Bacteriol. 199: 1-11.
- Christenson, J.K., Richman, J.E., Jensen, M.R., Neufeld, J.Y., Wilmot, C.M., Wackett, L.P. (2017) β-Lactone synthetase found in the olefin biosynthetic pathway. Biochemistry 56: 348-351. Accompanying commentary (Raushel, F.M. (2017) The discovery of a β-lactone synthetase. Biochemistry 56(9):1175-1176).
- Goblirsch, B.R., Jensen, M.R,, Mohamed, F., Wackett, L.P., Wilmot, C.M. (2016) Substrate trapping in crystals of the thiolase OleA identifies three channels that enable long-chain olefin biosynthesis. J. Biol. Chem. 291: 26698-26706.
- Evans III, R.L., Latham, J.A., Klinman, J.P., Wilmot, C.M., Xia, Y. (2016) 1H, 13C, and 15N resonance assignments and secondary structure information for Methylobacterium extorquens PqqD and the complex of PqqD with PqqA. Biomol. NMR Assign. 10: 385-389.
- Roessler, C.G. Agarwal, R., Allaire, M., Alonso-Mori, R., Andi, B., Bachega, J.F.R., Bommer, M., Brewster, A.S., Browne, M.C., Chatterjee, R., Cho, E., Cohen, A.E., Cowan, M., Datwan, S., Davidson, V.L., Defever, J., Eaton, B., Ellson, R., Feng, Y., Ghislain, L.P., Glownia, J.M., Han, G., Hattne, J., Hellmich, J., Héroux, A., Ibrahim, M., Kern, J., Kuczewski, A., Lemke, H.L., Liu, P., Majlof, L., McClintock, W.M., Myers, S., Nelsen, S., Olechno, J., Orville, A.M., Sauter, N.K., Soares, A.S., Soltis, S.M., Song, H., Stearns, R.G., Tran, R., Tsai, Y., Uervirojnangkoorn, M., Wilmot, C.M., Yachandra, V., Yano, J., Yukl, E.T., Zhu, D., Zouni, A. (2016) Acoustic injectors for drop-on-demand serial femtosecond crystallography. Structure 24: 631-640.
Education and 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