In the 20th century, X-ray crystallography revealed a molecular world at a level previously unimaginable, far beyond the limits of the microscope. However, X-ray structures are merely a static “snapshot” representing an ensemble average of rigid macromolecule states. Understanding the structural dynamics of biomolecular catalysis requires atomically resolved structures acquired continuously along an enzyme reaction pathway – a “molecular movie”. One of the few methods that provides this information is time-resolved (tr) crystallography.
In this project, we will study dye decolorising peroxidases (DyPs) via time-resolved techniques including x-ray crystallography and cryo-EM. DyPs are the most recent member of the peroxidase family to be discovered and differ significantly in protein fold to their counterparts (e.g., CcP and HRP). DyPs catalyse the oxidation of a wide range of substrates including anthraquinones, which are poor substrates for other peroxidases. Several DyPs can also catalyse some extraordinary reactions such as deferrochelation.
The mechanism of DyPs has been proposed to be similar to that of heme peroxidases, however contradicting literature exists. Furthermore, in contrast to other heme proteins our knowledge about DyPs is very limited. Using time-resolved techniques, we will investigate the mechanisms of DyP proteins to provide much needed structural clarity into deciphering the mechanistic features of this class of enzyme.
The ultimate goal is to obtain the structures with visible hydrogen atoms to create molecular movies of substrate turnover which will enhance our understanding of the catalytic mechanism and the role of conserved residues. To complement this study, neutron crystallography will also be carried out and the crystallography studies will be complemented with UV-vis spectroscopy in crystallo.
DyPs unique substrate specificity and catalytic properties offer great opportunities for exploring peroxidase enzymology and biotechnology application. This study will enhance our understanding of this new superfamily of peroxidases.
Entry Requirements:
- Those who have a 1st or a 2.1 undergraduate degree in a relevant field are eligible.
- Evidence of quantitative training is required. For example, AS or A level Maths, IB Standard or Higher Maths, or university level maths/statistics course.
- Those who have a 2.2 and an additional Masters degree in a relevant field may be eligible.
- Those who have a 2.2 and at least three years post-graduate experience in a relevant field may be eligible.
- Those with degrees abroad (perhaps as well as postgraduate experience) may be eligible if their qualifications are deemed equivalent to any of the above.
For further information please contact [Email Address Removed]
Application advice:
To apply please refer the application instructions at
https://le.ac.uk/study/research-degrees/funded-opportunities/bbsrc-mibtp
You will need to apply for the PhD place at University of Leicester and also submit your online application notification to MIBTP. Links for both are on the above web page.
Project / Funding Enquiries: For further information please contact [Email Address Removed]
Application enquiries to [Email Address Removed]
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