Mike Hough

profilephoto Email: Michael.Hough@diamond.ac.uk
Tel: 01235 394097
  • Room temperature crystallography, particularly of metalloproteins
  • Radiation damage in macromolecular crystallography
  • Serial crystallography (synchrotron and XFEL) to obtain low-dose or undamaged states
  • Time resolved and dose resolved crystallography to resolve enzyme mechanisms
  • Spectroscopic validation of crystal structures
  • Structural biology of metalloproteins and metalloenzymes

Mike Hough is Principal Beamline Scientist at VMXi. He joined Diamond in 2021 from the University of Essex where he was a Senior Lecturer in the School of Life Sciences. Before joining Diamond, he collaborated extensively with beamline scientists in methods development research.

His main research interests are in room temperature, dose or time-resolved and serial crystallography using synchrotron and XFEL beamlines including SACLA and LCLS. He has long-standing interests in the structural biology and biochemistry of metal-containing proteins including those involved in the nitrogen cycle, gas ligand binding and heme enzymes as well as in combining biology with molecular simulation, particularly using QM/MM.

 

Current research interests

Room temperature, Serial and Time Resolved Crystallography

In collaboration with Robin Owen and team at beamline I24, we have been utilising fixed target approaches to obtain low-dose synchrotron and effectively damage free serial XFEL structures of radiation sensitive metalloproteins. This work is also a collaboration with the Sugimoto laboratory at RIKEN and the group of Ivo Tews at Southampton University. We are also exploring time resolved crystallography using either light activation and photocages or drop on drop mixing in collaboration with the UK XFEL hub. Data are measured at Diamond, SACLA and LCLS and involve the combination of crystallographic and spectroscopic data. Finally, we have recently investigated the ability to resolve proteins and complexes in serial data as a function of the number of diffraction patterns analysed.

Enzymes of the nitrogen cycle  

I have a long-standing research interest in metal containing enzymes that are involved in the nitrogen cycle. Copper nitrite reductases catalyse the reduction of nitrite to nitric oxide in denitrifying organisms. We have used structural biology, biochemistry and spectroscopy to characterise the mechanism of these enzymes at cryogenic and room temperatures and to probe reactivity within crystals driven by x-ray generated photoelectrons (the MSOX approach, in collaboration with the Hasnain group at University of Liverpool). Damage free SFX structures have been produced by XFEL serial femtosecond crystallography. Working with the Keal group at STFC Daresbury laboratory we are combining structural movies of catalysis with advanced QM/MM simulations to define reaction pathways.

We are also studying cytochrome proteins in denitrifying, methanotrophic and nitrifying bacteria. Cytochromes c’ bind to and discriminate between diatomic gases as alpha helical proteins. We recently determined the first structure of a beta sheet cytochrome c’ and its related enzyme, cytochrome P460 from a methanotrophic organism. Enzymes that contain a P460 cofactor are unusual but are critical for the oxidation of hydroxylamine in the process of nitrification that allows fixed nitrogen to become bioavailable.

Heme peroxidases

We have an ongoing research programme into the structure and mechanism of heme peroxidases. In collaboration with Jonathan Worrall at the University of Essex we are defining the mechanism and structural states of dye decolourising peroxidases from the antibiotic producing organism Streptomyces lividans. These enzymes utilise high valent iron centres for catalysis, which raises challenges to obtain intact structures of Fe(III) and Fe(IV) states which are rapidly changed by radiation damage. We recently determined structures of both these redox states for the first time at room temperature and 100 K (with the cryogenic data using a multi-crystal, spectroscopically validated approach). In collaboration with the Ghiladi group at North Carolina State University we are investigating the fascinating multifunctional globin, Dehaloperoxidase that is able to catalyse peroxidase, oxidase, oxygenase and peroxygenase reactivities.

 

Collaborations

Jonathan Worrall, University of Essex: structural biology and mechanistic studies of iron and copper proteins from Streptomyces lividans.

Robin Owen (Diamond), Hiroshi Sugimoto, (SPring-8) and Ivo Tews (Southampton): serial crystallography and XFEL experiments of metalloproteins. Allen Orville (Diamond) and colleagues, Chris Schofield (Oxford): drop on drop mixing and SFX-XES.

Reza Ghiladi (North Carolina State University): Structural and mechanistic studies of the multifunctional globin, dehaloperoxidases from the marine annelid, Amphitrite ornata.

Colin Andrew (Eastern Oregon University): Cytochrome c’ and cytochrome P460 proteins

Thomas Keal (Scientific ComputingDepartment, STFC): Combining dose resolved and time resolved crystal structures with molecular simulations.

 

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