NMR STUDIES OF THE MECHANISMS OF ACTION OF TRP-REPRESSOR

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The long term objectives are to understand at the molecular level the recognition of specific sequences of DNA by repressors, and the allosteric modulation of this recognition process by metabolites. The specific aims are to investigate the thermodynamics and mechanism of the interaction of the trp repressor with its operator DNA and other, non-operator DNA sequences, in the presence and absence of specific modulatory molecules (tryptophan and desaminotryptophan). The repressor protein and the DNA will also be extensively characterized, both structurally and functionally, using advanced high resolution NMR methods, particularly two dimensional techniques and measurements of relaxation times. Once the components have been fully characterized, the changes that occur on forming various complexes will be compared, and detailed information regarding the molecular basis for such recognition will be available. These recognition processes are an integral part of the control of gene expression a topic which lies at the heart of modern molecular biology and relates indirectly to the development of suppression of certain kinds of cancer.