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The University of Southampton
Structural BiologyPart of Biological Sciences

Enzymology

Protein crystallography is an ideal technique to study enzymatic systems. High-resolution atomic definition has been instrumental for example in our understanding of protease enzyme catalysis. Investigation of large multi-protein enzyme complexes reveals mechanisms of activation and regulation between interacting enzymes.


PLP synthase is a 24 protein complex required in the synthesis of Vitamin B6
PLP synthase helps make Vit B6

PLP synthase is a 24 protein complex, required for synthesis of vitamin B6. These complexes have a total molecular weight of up to 750kDa and contain nearly 6000 amino acids. Study of the enzyme complex has revealed activation of the glutaminase subunit by interaction with the synthase. An internal intermediate tunnel is identified that allows reactive ammonia to transfer between catalytic subunits. The PLP synthase subunit has a substrate and a product site, and requires two carbohydrates as well as ammonia produced by the glutaminase. Since vitamin biosynthetic pathways are essential for survival for many pathogens, and since they are absent in humans, they represent potential targets for antimicrobial and antiparasitic therapies.

PLP synthase from the malaria pathogen Plasmodium (January 2012) is a research project supported by the EU and a collaboration with Prof Steve Ealick of Cornell University and the Diamond Light Source.
This work was awarded with the David Blow Prize 2011 and discussed in articles here and here.

PhD: Matthew Rodrigues
Supervisors: Dr Ivo Tews, Dr Gwyndaf Evans
PhD research: Catching Reaction Intermediates in the Multi-step PLP biosynthesis with Microfocus Synchrotron Techniques in situ.

Funding: Diamond Light Source and University of Southampton
Primary research group: Molecular and Cellular Biosciences


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