Peter Moody

Enzyme structure and function

Research summary

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We try to unravel enzyme mechanisms and investigate the way biological molecules recognise both smaller molecules and each other. Our primary technique is crystallography, X-ray crystallography is a very powerful technique that gives the three-dimensional structures of molecules, but the positions of hydrogen atoms are normally invisible. By using neutrons whose wavelength is similar to that of X-rays we are also able to determine the positions of these hydrogens. Together, neutron and X-ray crystallography allow us get detailed pictures of the interactions of biomolecules. Neutron crystallography has an additional advantage in that it avoids the ionising effects of X-irradiation. We use the nuclear reactors at the Institut Laue Langevan in Grenoble and MLZ Munich and the spallation source at Oak Ridge National Laboratories in Tennessee for neutrons and collaborate with the scientists at these facilities.

Because enzyme reactions are dynamic, we need ways to trap the intermediates in our crystals, and in order to follow the reactions we need to find ways to monitor them. In solution this is often done with spectrophotometry. We have a system for single crystal spectrophotometry that allows us to test if our methods of catching the various steps in the reaction have worked. We can then trap these intermediates in the crystal at low temperatures. Because we work with redox sensitive enzymes some of the work is done in our anaerobic glove box, this also houses a crystallisation robot.

Our work on heme peroxidases is in collaboration with Emma Raven, our studies on molecular recognition in the complement system have been done with Russell Wallis. We also work on the enzymes in key metabolic pathways in pathogens, for example gluconeogenesis in enteric pathogens.

Key publications

Group members

Chinar Pathak