Metal ions are essential for many biochemical processes. The natural selection of certain metals for specific physiological roles represents a true marriage of chemistry and biology. From a biological perspective, the intrinsic properties of the ‘selected’ metal enable vital chemistry to take place efficiently, often with minimal or no additional thermodynamic driving force required. From a chemical perspective, the 3D structure and coordination environment provided by a protein is responsible for fine-tuning the properties of the metal centre to bias reactivity in favour of the desired outcome. Nature often repurposes both metals and coordination environments in order to achieve a wide range of chemical reactivity from structurally similar building blocks. WG3 will address these differences in function and reactivity, pioneering the use of complementary, and often concurrent, structural and spectroscopic methods to address problems in the chemical biology of metals.
An ability to control reactivity is becoming increasingly important if the biophysical community is to exploit fully the power of next generation X-ray, neutron, and XFEL sources. This working group will develop and promote the use of novel sample environments including, but not limited to, the use of electrochemistry to prepare specific catalytic intermediates, and the combination of stopped-flow and freeze quench methods to catch enzymes in the act. WG3 will also initiate discussion of different ways to trigger an enzyme reaction, and the best data collection strategies for catching elusive intermediates. To gain a deeper understanding of the molecular mechanisms, we will combine the experimental methods with computational simulation and analyses.
Chemistry of Life Core Group leader, LINXS Fellow
Andrew Hudson, Professor of Biophysical Chemistry, Institute for Structural and Chemical Biology, University of Leicester, UK.
Prof Hudson is a biophysical chemist with research interests in the application of specialised techniques in fluorescence imaging to monitor the dynamics of single molecules. He has been applying these methods to address otherwise inaccessible problems in RNA splicing. These have included validation of the spice-site selection model and the pathways for the early stages of spliceosome assembly and 3′ splice-site selection. On a different note, he has applied a number of different imaging modalities to quantifying the distribution of haem proteins in living cells, and how this evolves in response to different stimuli. Recently, he has been looking at the regulatory role of haem in cells, and designed a genetically-encoded sensor for measuring in vivo haem concentrations by fluorescence lifetime imaging. His research group has also developed new fluorescence assays to probe the role of haem in the molecular mechanism of the transcription-translation feedback loops which are responsible for maintaining circadian rhythms.