This proposal requests funds to use the three dimensional structure at 2.8 A resolution of an important metabolic enzyme, 2-keto-3-deoxy-6-phosphogluconate (KDPG) aldolase which is found in Pseudomonas putida and many other microorganisms to provide a well defined structure of the active-site region, which can then serve as a general model of aldolytic catalysis. A major activity will be the development of the architecture of the active site, and reconciling the vast amount of information already available about the active site of KDPG aldolase. The latter will be aimed at understanding the mechanism (amino acids involved in catalysis), stereochemistry (spatial aspects of mechanism) and specificity of the enzymic expression. This is to be accomplished with X-ray crystallographic procedures using crystals of KDGP aldolase derivatized with various substrate analog sugars and/or fragments thereof. These studies will be guided by the results of solution studies.