Mike Hough Structural Biology and Biophysics. Main research questions How does protein structure relate to function? How is ligand discrimination in heme.

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Presentation transcript:

Mike Hough Structural Biology and Biophysics

Main research questions How does protein structure relate to function? How is ligand discrimination in heme proteins achieved & controlled? How can we ensure that structural information is correct? How can we gain the maximum information from a structural biology experiment? Can enzyme reactions be followed in crystals?

Techniques and approaches X-ray crystallography and complementary spectroscopy Method development for single crystal spectroscopy and in crystal reactions Site-directed mutagenesis and biochemical analysis Kinetics (in house and ultra-fast) EPR We have continuing access to Diamond Light Source (with UEA and John Innes) and Swiss Light Source Recombinant expression and purification

Cytochromes c’ (CYTcp) Cytochromes from denitrifying and photosynthetic bacteria Discriminate between NO, CO and O 2 Varying ligand binding between species His 120 Leu 16 Arg 124 Trp56 Phe 86 Gln 83 Gln 87 Asp 121 Proximal Distal Hough et al (2010) J. Mol. Biol. 405, Russell et al (2013) FEBS J. accepted

Structure 37: Product NO- bound species 1.3 Å Low-dose structure 1 (1.33Å) Substrate bound T1Cu reduction Structure 5: 1.22Å T1Cu reduced to Cu(I) T2Cu unchanged Structure 20: Cu-nitrite Asp92 single Conformation 1.25Å Structure 54: Ligand dissociation and Asp disorder 1.9 Å NO Driving reactions in Crystals

Swiss Light Source Florian Dworkowski Crystal Raman & UV-vis External Collaborations Diamond Light Source Robin Owen (method development) Nigel Scrutton, Manchester (& STFC Central Laser Facility) Ultrafast kinetics, TRIR, TA Colin Andrew Eastern Oregon University Solution resonance Raman Antoine Royant, ESRF University of Liverpool Driving reactions in multi-copper proteins Synchrotron method development

Collaborations in the Department Jonathan Worrall Cu proteins from Streptomyces Cytochrome c Dima Svistunenko Ligand binding to cytochromes c’ Brandon Reeder Plant hemoglobins Cytoglobin Mike Wilson Peter Nicholls Kinetics, laser-flash, redox ‘Embryonic’ collaborations with others. Phil Reeves Rhodopsin

Collaborations and Ideas I can offer… Crystallisation and X-ray experiments for your project - preliminary data for grants Co-supervision of students for structural-biology related projects Where I would like to collaborate further: Proteomics Cell or organism-level work