Phosphonates are chemically stable phosphate ester analogs and as such find widespread use as herbicides, pesticides and pharmaceutical agents. Their physiological function in higher organisms is largely uncharacterized, but evidence that links them to cell signaling processes has been reported. We have isolated an enzyme that catalyzes phosphonate P-C bond formation in Tetrahymena pyriformis and in salt water mussel. We are currently looking for this same enzyme in plants and mammals. Studies are presently being conducted to define the biosynthetic and biodegradative pathways of phosphonates and the mechanisms of the enzymes catalyzing P-C formation and cleavage.
Phosphonate biochemistry is a new and exciting frontier in biological chemistry.
A third area of study is concerned with the mechanism and dynamics of domain movement within proteins. For proteins in which function is coupled with physical translocation, the use of structural domains to mediate movement is common. For instance, catalysis at separate active sites in multi-enzyme complexes is often seen linked by a carrier arm transported by movement of the domain to which it is appended. On a smaller scale, catalysis of the ATP and pyruvate partial reactions in the enzyme pyruvate phosphate dikinase takes place at two different active sites linked by a carrier histidine.