CRYSTALLOGRAPHIC STUDIES OF TRANSPORT PROTEINS FROM ESCHERICHIA COLI

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The goal of this subproject is to purify in sufficient amounts two intrinsic membrane proteins of Escherichia coli, the OmpA protein of the outer membrane and the multi-subunit, maltose transporter complex of the inner, cytoplasmic membrane, and to carry out the electron crystallographic studies of these membrane proteins. OmpA was chosen because it belongs to a family of novel porins, with unusually low permeability, and the structural basis for this property is total unknown. The elucidation of the channel structure of this protein is expected to help design better chemotherapeutic agents, which would be more effective against Pseudomonas aeruginosa, that is a major source of opportunistic infections because it has an OmpA homolog, a low permeability porin, as its main porin. The maltose transporter complex was chosen because it is one of the best-studied members of a widespread transporter family, the ABC ("ATP-binding cassette") transporters, and much knowledge is available on the physiology and genetics of this transporter. The ABC transporters include the MDR system of mammalian cells, which pumps out anti-cancer agents from the cytoplasm of cancer cells. Thus the understanding of the molecular structure and mechanism of action of maltose transporter, as a paradigm of the ABC transporters, is expected to contribute to the design of anti-cancer agents that may remain active even in cells expressing the MDR system at a high level.