The main focus of our research is the structure-function relationships of the enzyme creatine kinase. Creatine kinase is a critical component of the regulatory mechanisms of various eergy requiring processes in both simple and complex life forms, including humans. Skeletal and cardiac muscle movement, as well as active transport across membranes are a few of the biological reactions that rely on the action of creatine kinase. Not only does creatine kinase provide a mechanism for storage of cellular energy in the form of high-energy phosphate bonds, but more recently there is evidence of creatine kinaseUs role in transporting the fuel necessary to drive important bioprocesses. Many isoforms of creatine kinase are known to exist and each has shown tissue-specific differences that undoubtedly relate to the unique functions peculiar to the cellular location of each isoenzyme. Most notably creatine kinase isoforms are found in muscle, brain and two forms in mitochondria. We are using the facilities of the Computer Graphics Laboratory and in particular, the powerful modelling program MidasPlus, in comparative analyses of the various creatine kinase structures. We are comparing the major isoforms of creatine kinase and also site-directed mutant forms of the enzyme that have, or will be, generated by our laboratory. The ultimate goal is to rationalize the wealth of enzymatic data with the structures now available and to predict and design new functions based on alteration of these structures. Additionally, the creatine kinase system will be used as a model system for the development of new computational tools to model structure-function relationships in enzymes that exist in multiple forms within an organism. The tools available through the CGL are instrumental to these efforts.
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