Chemical Biology of Terpenes
With more than 55,000 known compounds serving myriad functions in all forms of life, the terpenoids are the largest as well as the most structurally and stereochemically diverse family of natural products found on earth.
Dihydrofolate Reductase & the Physical Basis of Enzyme Catalysis
The hallmarks of catalysis by enzymes are selectivity, specificity, and speed. However, despite their central role, the physical basis of the enormous catalytic power of enzymes is not well understood.
Recent mapping of all physical interactions between proteins in a given cell has confirmed the notion that interactions between proteins are highly regulated and underpin all cellular processes. Researchers and technologists have been presented with a major challenge – how to ask specific questions of such complex systems especially when protein interactions change with time in a given cell and result in different end states.
The movement of white blood cells, especially neutrophils and lymphocytes, from the blood to the tissues is the key event underlying inflammation. Understanding the mechanism by which these cells adhere to the cells lining the blood vessels is clearly important, as this would be a potential target for anti-inflammatory therapy. Research at Cardiff has found that changes in the concentration of calcium cations within the cells is crucial for this and there is increasing evidence that the calcium cation-activatable protease calpain-1 is also involved.
Terpene synthases catalyse complex, multistep reactions that generate thousands of structurally diverse hydrocarbons of biological and commercial importance. Unlike many other biochemical reactions, terpene biosynthesis is essentially carbocationic in nature. Previous work in our lab has revealed many of the mechanistic details of the conversion of FPP by aristolochene synthase (AS), but the key step, the generation of the positively charged eudesmane cation from the uncharged intermediate germacrene A is only poorly understood.
For further details on any of these areas, see our recent publications.