Abstract
A molecular structure determined by crystallography, cryo-EM, or NMR is an excellent starting point for our understanding of how biology is accomplished, but NMR is one of the best tools for going beyond this starting point for a detailed characterization of functional mechanisms, even for an understanding of kinetic rates. To this end one of the best approaches for doing this is through the observation of isotropic and anisotropic chemical shift perturbations. Two molecular systems that have been extensively studied and characterized exemplify the usefulness of chemical shift perturbation as an effective strategy for understanding functional activities. Gramicidin A, an antibiotic from Bacillus brevis, that as a dimer forms a monovalent cation channel and a protein from Influenza A virus, the M2 protein that as a tetramer forms a proton channel. Blocking the M2 proton channel is an effective anti-influenza strategy. For gramicidin it was discovered that different monovalent cations have different binding sites at the mouth and exit of the channel accounting for the different solvation energy requirements of the various cations. For M2 the functional activity of a unique histidine tetrad that shuttles protons into the viral interior through a balance of futile and conductance protonation cycles was elucidated by chemical shift perturbations.
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Chekmenev, E.A., Paulino, J., Fu, R., Cross, T.A. (2017). Anisotropic and Isotropic Chemical Shifts Perturbations from Solid State NMR Spectroscopy for Structural and Functional Biology. In: Webb, G. (eds) Modern Magnetic Resonance. Springer, Cham. https://doi.org/10.1007/978-3-319-28275-6_87-1
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DOI: https://doi.org/10.1007/978-3-319-28275-6_87-1
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