STRUCTURE AND ACTIVITY OF MEMBRANE TRANSPORT PROTEINS

拟议调查的总体目标是测试

The overall objective of the proposed investigation is to test the hypothesis that seemingly dissimilar transport proteins have a common mechanism of action which is dictated by a common structure. Membrane transport proteins serve essential functions in the metabolism of normal eucaryotic and procaryotic cells, are causative agents in several disease states, and determine the therapeutic efficacy of various drugs. Therefore, understanding the fundamental processes of substrate recognition and transport at the molecular level, and then ultimately being able to alter these processes, has significant potential importance in food production, biotechnology and medicine. Specifically, we propose to use site-directed mutagenesis and gene fusion techniques in combination with membrane transport assays to test the hypothesis that the activities of several seemingly diverse transporters are dependent upon a subset of highly conserved amino acid residues which are conserved in various transport proteins, including the tetracycline resistance proteins (Tet) and several sugar transporters of gram negative bacteria. Tet and sugar transporters are alike in the prediction of twelve membrane-spanning regions and in the conservation of certain motifs which yield significant levels of similarity in statistical tests. The three dimensional structures of these proteins are likely to be similar with relatively subtle structural differences that account for their recognition of different substrates, implying fundamentally similar molecular mechanisms.