Vitamin B6 Biosynthesis
Vitamins are low molecular weight compounds which have to be taken up into our cells in trace amounts, and vitamin deprivation leads to disease. In the body, vitamins often serve as enzymatic cofactors. Studies of their biosynthesis by human pathogens are of particular interest in order to develop specific drugs.
The main pathway for de novo vitamin B6 biosynthesis is a recent discovery. We address the architecture of key enzyme complex, PLP synthase and study protein-protein interaction, complex formation, activation of the enzymes and the biosynthesis of the vitamin by the enzyme complex.
Protein transport across cell membranes
Cell survival critically depends on transport. Metabolic products have to be transferred into and out of the cell, and proteins are secreted. Inside the cell there is transport as well, for example into and out of organelles. These transport phenomena involve transfer across membranes. We study plant chloroplast protein import as one example. Proteins required for photosynthesis are mainly synthesized in the cytosol of plant cells, and thus need to be transported into the organelle. Protein transport is mediated by the Toc-Translocon in the outer chloroplast membrane. The GTPases investigated by us are receptors of protein import.
Mycobacterial Adenylyl Cyclases
The Mycobacterium tuberculosis genome has 15 open reading frames for class III adenylyl cyclases (ACs). We investigate ACs that respond to environmental pH and lipid composition. The proteins contain a regulatory domain at the N-terminus and a class III cyclase homology domain (CHD) at the C-terminus. Depending on regulatory stimuli, the CHDs dimerise to form the active enzyme. The activated enzymes produce the universal second messenger cAMP from ATP. Reorientation of the catalytic domains on pH change leads to inactivation, while a dimeric structure is retained through interaction of the regulatory domains.
Molecular and Cellular Biosciences
Affiliate research group(s)
Dr Ivo Tews
Faculty of Natural & Environmental Sciences
Life Sciences Building 85
University of Southampton
Room Number: 85/4041
Telephone: (023) 8059 4415