Tuberculosis has re-emerged as a global health concern due to a rise in anti-Mycobacterial drug-resistant strains. Discovery of novel drug targets are complicated by the need to penetrate the thick cellular envelop of Mycobacteria. However, it has been recently discovered that Mycobacterium tuberculosis secretes Glutamine Synthetase into its immediate environment (Harth et al. 1994) and that inhibition of this secreted enzyme disrupts normal development (unpublished data). Determining the structural models described in this proposal will serve as a starting point for the design of drugs that bind to and inhibit its action, hence providing new therapies to combat this disease. Protegrin is a remarkably potent antibiotic peptide, effective as both an antimicrobial and an antiviral agent. Given the small size and relatively simple structure of protegrin, it provides an attractive template for designing potentially useful chemoprotective peptides. However, the methods by which antimicrobial peptides discriminate between cell types, and ultimately destroy an invading cell is poorly understood. By characterizing specific interactions between protegrin monomers in the crystal lattice, we will gain insight into understand the possible mechanisms of action for protegrin. D-lactate dehydrogenase (D-LDH) is a membrane-associated respiratory enzyme. It provides unusual opportunity for studying the relationship between structure and function in a peripheral membrane protein. Determining the three-dimensional structure of D-LDH will help understanding the protein-protein and protein-lipid interactions in, the poorly understood peripheral membrane proteins.