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Structural Biology of Membrane Transport Proteins

$36,592F32FY2002GMNIH

University Of California San Diego, La Jolla CA

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Abstract

DESCRIPTION: (provided by applicant) The goal of the proposed research is to investigate the structural biology of the proteins that bind and transport heavy metals ions. Proteins from the bacterial mercury detoxification system are the principal objects of this study. There is a direct molecular connection between the mechanism by which bacteria detoxify heavy metals and a number of diseases, because of the high level of homology among many proteins responsible for binding heavy metals in bacteria and humans. The immediate goal of the research is to determine detailed structures of the membrane proteins MerT and MerF, responsible for transport of the Hg(II) ions in the cell, where reduction to Hg(O) occurs. We intend to do so by using Nuclear Magnetic Resonance (NMR) spectroscopy. Solving this problem will concurrently be instrumental to the development of a general methodology for structure determination of membrane proteins. The structures of the proteins that bind and transport heavy metals in bacteria will provide a molecular model to understand diseases related to improper heavy metal transport and to exposure to heavy metal toxins.

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