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NMR Studies of Membrane Proteins

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Membrane Transporters in Drug Discovery and Development

Part of the book series: Methods in Molecular Biology ((MIMB,volume 637))

Abstract

Nuclear magnetic resonance studies of membrane proteins yield valuable insights into their structure and topology. For example, the tilt angle and rotation of the helices in an ion channel can be determined by solid-state NMR spectroscopy in aligned lipid bilayers. Details about the structure of the protein in aligned phospholipids environments are immediately apparent from inspection of the SAMMY spectrum and the data can be further used for the determination of atomic resolution three-dimensional structures. SAR by NMR is a technique that is well suited for the field of membrane transporter proteins. The experiments on protein/phospholipid samples provide a unique insight into the interaction of drugs and the functional proteins.

The advances required to transform solid-state NMR from a spectroscopic technique to a generally applicable method for determining molecular structures included multiple-pulse sequences, double-resonance methods, and separated local field spectroscopy. It also required improvements in instrumentation, especially the use of high-field magnets and efficient probes capable of high-power radio-frequency irradiations at high frequencies. The pace of development is accelerating and the local field is being utilized in an increasing number of ways in spectroscopic investigations of molecular structure and dynamics. Applications to many helical membrane proteins are underway and promise to add to our understanding of membrane proteins in health and disease.

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Acknowledgments

This research was supported by grants from the National Institutes of Health; it utilized the Biomedical Technology Resource for NMR Molecular Imaging of Proteins, which is supported by grant P41EB002031; and G.A.C. received support from Training Grant 5T32DK00723332. We thank Gilead Sciences, Inc., for support.

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Authors and Affiliations

  1. Department of Chemistry and Biochemistry, University of California San Diego, La Jolla, CA, USA

    Gabriel A. Cook & Stanley J. Opella

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  1. Gabriel A. Cook
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  2. Stanley J. Opella
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Editors and Affiliations

  1. PharmTao, Santa Clara, USA

    Qing Yan

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Cook, G.A., Opella, S.J. (2010). NMR Studies of Membrane Proteins. In: Yan, Q. (eds) Membrane Transporters in Drug Discovery and Development. Methods in Molecular Biology, vol 637. Humana Press. https://doi.org/10.1007/978-1-60761-700-6_14

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  • DOI: https://doi.org/10.1007/978-1-60761-700-6_14

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  • Publisher Name: Humana Press

  • Print ISBN: 978-1-60761-699-3

  • Online ISBN: 978-1-60761-700-6

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