Enzyme mechanism through advanced techniques

Qualification: PhD

Department: Molecular and Cell Biology

Application deadline: Open Until Filled

Start date: September 2019

Overview

This studentship is for up to 4 years and supported by a Royal Society Wolfson Fellowship

Project Description

“Traditional” protein X-ray crystallography has contributed enormously to our understanding of enzyme mechanisms. However, hydrogen atoms are not often seen, and the X-rays induce changes that may alter the chemical state of key catalytic components; this is a problem especially for redox enzymes.  A number of approaches can be used to avoid some of these difficulties. 

One is neutron crystallography, as neutrons can show hydrogen positions and another is to use X-ray free-electron lasers (XFELs) which produce femtosecond pulses of X-rays, allowing diffraction data to be collected before damage can take place. Developments and improvements at synchrotron sources now let us collect diffraction data from very small crystals in milliseconds at room temperature. Electron crystallography is advancing quickly and could lead to detailed description of the electrostatic surfaces in enzyme active sites. 

Using single crystal spectroscopy and neutron crystallography we have been able to see the hydrogen positions in catalytic intermediates of heme peroxidases. This project aims to take advantage of the latest exciting developments in structural biology techniques to explore the catalytic mechanisms of these and other redox enzymes. LISCB is well equipped for structural biology (see https://www2.le.ac.uk/institutes/liscb/facilities-and-technologies ). We expect to undertake external experimental work at the Diamond Light Source synchrotron near Oxford, the Neutron sources in Grenoble, Munich or Tennessee, and the XFELs in Japan and Hamburg. 

References

• Casadei CM, et al. (2014) 'Heme enzymes. Neutron cryocrystallography captures the protonation state of ferryl heme in a peroxidase.' Science, 345. Pp. 193–197.
• Kwon H, et al. (2016) 'Direct visualization of a Fe(IV)-OH intermediate in a heme enzyme.' Nat Commun, vol. 7. P. 13445.
Moody, PCE  & Raven EL (2018) The Nature and Reactivity of Ferryl Heme in Compounds I and II  Acc. Chem. Res. 51 (2), pp 427–435

Supervisors

Professor Peter Moody

Dr Jaswir Basran

Funding

Funding

This studentship is for up to 4 years and supported by a Royal Society Wolfson Fellowship to Professor Moody

UK/EU tuition fee waiver 

Stipend at UKRI rates, which for 2019 will be £15,009 p.a

Entry requirements

Entry requirements

Applicants are required to hold/or expect to obtain a UK Bachelor Degree 2:1 or better in a relevant subject or overseas equivalent.

The University of Leicester English language requirements apply where applicable.

Informal enquiries

Informal enquiries

Project enquiries

Professor Peter Moody

Application enquiries

pgradmissions@le.ac.uk

How to apply

How to apply

To apply, please use the Apply button at the bottom of the page

  • In the funding section, please state you are applying for the Royal Society Wolfson Fellowship.
  • In the proposal section, give the supervisor’s name and project title.
  • Include a personal statement stating why you should be considered for the studentship.

Eligibility

Eligibility

  • UK/EU applicants only