Protein NMR
Prof M P Williamson |
Career History2001-present: Professor, University of Sheffield |
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| We have been developing new tools to characterise volume fluctuations in proteins, which occur on timescales between ns and ms. In particular, we have shown that changes in the NMR spectrum resulting from hydrostatic pressures of up to 2 kbar can be used to show how proteins move, and also how they start to denature under pressure. The mobilities are greatest at the active site, and usually involve buried water molecules, which are very important for increasing local flexibility (Figure 1). |
| We have demonstrated that exposed salt bridges are not energetically favourable in solution, even though they are often observed in crystals |
| In collaboration with Prof Hunter in MBB, we have determined structures for two trans-membrane proteins involved in bacterial light-harvesting. The structures are very similar in organic solvents and in micelles. These structures have been used to model the intact photosynthetic complex |
| We have studied how proteins recognize polysaccharides such as starch, cellulose and xylan. The activities of enzymes that degrade these plant polymers tend to be organized into ‘cellulosomes’ which are large assemblies of many different enzymes. We have determined the structure of the key assembly component of the anaerobic cellulosome and showed that it probably relies on protein / carbohydrate recognition to assemble |
| We have a longstanding interest in polyphenols such as those from tea, and in how they interact with the body. As part of this study, we have shown that the main component of green tea, epigallocatechin gallate, has the potential to slow down HIV infection. |
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 Figure 1– Slow fluctuations in the ribonuclease barnase. In blue are residues that become significantly less mobile on binding to ligands (shown in red). These residues define a ‘hinge-bending’ region important for ligand binding. The spheres show the location of buried water molecules. |
find me on Google Scholar |
Selected PublicationsBook published July 17 2011: Chapter 1 Protein structure and evolution; Chapter 2 Protein domains; Chapter 3 Oligomers; Chapter 4 Protein interactions in vivo; Chapter 5 How enzymes work; Chapter 6 Protein flexibility and dynamics; Chapter 7 How proteins make things move; Chapter 8 How proteins transmit signals; Chapter 9 Protein complexes: molecular machines; Chapter 10 Multi-enzyme complexes; Chapter 11 Techniques for studying proteins.
For a list of selected publications, see here. |
My laboratory uses NMR (and other methods where appropriate) to determine the structure and dynamics of proteins in solution and to study their interactions with ligands. In addition we are developing new methods for characterising structures. Further details are in my web page, linked on the right. Recent work includes: