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Biophysics of enzyme-catalyzed phosphoryl transfer

  • Full or part time
  • Application Deadline
    Applications accepted all year round
  • Self-Funded PhD Students Only
    Self-Funded PhD Students Only

Project Description

Using a combination of multinuclear NMR spectroscopy, high resolution X-ray crystallography, synthetic chemistry and computational chemistry we have explored the conformational behaviour of enzymes under a very wide range of conditions. Recently, our group has focused on enzymes that catalyse the transfer of phosphoryl groups, where the non-catalysed reactions can be among the slowest known for a physiological process: phosphate monoesters, for example, have calculated lifetimes to spontaneous hydrolysis of up to 1012 years. We are using a range of phosphoryl transfer enzymes to illustrate what contributes to the very high levels of catalysis achieved by these enzymes. The introduction of metal fluoride species to mimic the ground states and the transition state of the transferring phosphate group has allowed us to dissect the steps involved in catalysis, and to dissect electronic contributions made by the enzymes. In particular, these enzymes illustrate how the enzyme tightly controls charge distribution in the close vicinity of the transferring phosphate, and how the near transition state complex conformation reacts to modulation of these charges. Now, we will extend these observations to detail how phosphoryl transfer enzymes control domain closure, and how the distribution of protons plays key roles in controlling catalysis.

Science Graduate School

As a PhD student in one of the science departments at the University of Sheffield, you’ll be part of the Science Graduate School – a community of postgraduate researchers working across biology, chemistry, physics, mathematics and psychology. You’ll get access to training opportunities designed to support your career development by helping you gain professional skills that are essential in all areas of science. You’ll be able to learn how to recognise good research and research behaviour, improve your communication abilities and experience technologies that are used in academia, industry and many related careers. Visit http://www.sheffield.ac.uk/sgs to learn more.



Funding Notes

Entry requirements
First class or upper second 2(i) in a relevant subject. To formally apply for a PhD position, you must complete the University's application form using the following link: View Website

*All applicants should ensure that both references are uploaded onto their application as a decision will be unable to be made without this information*.


How good is research at University of Sheffield in Biological Sciences?

FTE Category A staff submitted: 44.90

Research output data provided by the Research Excellence Framework (REF)

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