The research group of Professor Carrie Wilmot in the Department of Biochemistry, Molecular Biology, and Biophysics concentrates on understanding the synthesis and function of novel organic, organometallic, and metal-ion cofactors in proteins. (A cofactor is a chemically reactive protein modification or bound non-protein compound that is necessary for the biological activity of a protein, many of which are enzymes.) The ultimate goal of the research is to provide a basis for the development of new and better drugs, for engineering proteins for applications in biotechnology, and for designing simpler industrial catalysts. The researchers’ primary tool is macromolecular X-ray crystallography and mass spectrometry.
The Wilmot group recently published a paper in the Proceedings of the National Academy of Sciences, U.S.A. that describes the actions of the enzyme MauG to catalyze the formation of a tryptophan tryptophylquinone (TTQ) cofactor to activate the enzyme methylamine dehydrogenase (MADH) (“Diradical Intermediate Within the Context of Tryptophan Tryptophylquinone Biosynthesis,” ET Yuki, FG Liu, J Krzystek, S Shin, LMR Jensen, VL Davidson, CM Wilmot, AM Liu, PNAS, 110(1):4569, DOI: 10.1073/pnas.1215011110 (2013)). The oxidation process that results in the formation of tryptophan tryptophylquinone has three distinct steps; the researchers have been able to figure out the progression of the oxidation and identify the structures of the intermediate steps. The computer work was done at MSI’s BSCL. The image above shows the various steps of the process.
Image description: (A) Electron density for the precursor TTQ site in MauG–precursor MADH crystals of different ages. Electron density maps (blue) for the crystals aged for 10, 40, 50, and 130 days were generated from the respective refined structures. The 50- and 130-day electron density images were calculated using the refined 50-day model (cross-linked precursor TTQ) to enable visualization of the positive-difference electron density (green) for the appearance of the second oxygen. (B) The observed rotation in βTrp57-OH during cross-link formation. The figure was produced using PyMOL (www.pymol.org). Image and description © 2013 by National Academy of Sciences, USA.
posted on August 14, 2013