Calmodulin (CaM) is a Ca2+dependent regulatory protein which activates a variety of enzymes and evidently serves an important role in cellular metabolic regulation. A mechanistic model has been developed to explain how CaM activates enzymes and this model predicts the behavior of several enzymes reasonably well. However one enzyme, NAD kinase from peas, differs significantly from other CaM- activated enzymes in several important ways and does not appear to fit the model. The proposed experiments will determine the cause of this unique behavior by probing the thermodynamics of activation, the site of interaction with CaM, and the domain structure of NAD kinase. The results of these studies will lead to a better understanding of the unique behavior of NAD kinase, which should, in turns, contribute to our knowledge of how CaM performs it roles in cellular metabolism.
