We are carrying out detailed structure and function analysis of all these different forms of PPases to find out how these enzymes are related: merely in terms of stoichiometry of chemical mechanism, or is there some deeper protein structural/ functional relationship? While doing so, we will also learn how biological phosphorylation, Pi:PPi equilibration, is coupled to proton pumping. Studying this coupling with monomeric membrane-bound PPase is particularly attractive since with this enzyme the multiple interpeptide interactions do not complicate the analysis, as is the case with the structurally much more complex ATP-synthases. Our studies are mainly basic research, but we are also trying to exploit the differences observed between prokaryotic and eukaryotic PPases in developing PPase specific antimicrobials. Furthermore, we are cloning and expressing human PPase hoping to get important tools for treating diseases related to PPi metabolism, such calcium pyrophosphate dihydrate deposition disease, a major form of arthrophy, especially in the elderly.