This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Multi-drug resistance is a very significant health problem that has both medical and pharmacological concerns. The cause of the mdr phenotype is the result of a net decrease in the concentration of drug levels within the cell. This reduction occurs by two fundamental mechanisms that either lowers the membrane permeability, which leads to a decreased rate of drug entry across the lipid bilayer (Class I), or directly increasing the rate of drug removal from the cell (Class II). Both of these mechanisms are accomplished via a series of energy-dependent energy efflux pumps. Recently, we have obtained 3D crystals of a second distinct class of mdr transporters (Class II). The goal of this proposal is to determine the atomic structure of these mdr transporters. Hence, we will be able to discover the structural basis of mdr for this family of integral membrane proteins. We propose to screen and collect data from our membrane protein crystals and solve the structure of mdr transporter at SSRL.
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