I like to move it, move it…

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Mar 27, 2019
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In today’s issue of Science, there’s a nice review on protein dynamics by Mittermaier & Kay and a paper on the dynamics and function of a peptidyl carrier protein domain of tyrocidine A synthetase. In their review, Mittermaier & Kay wrote:

Recent methodological advancements in NMR have extended our ability to characterize protein dynamics and promise to shed new light on the mechanisms by which these molecules function … NMR spectroscopy is uniquely suited to study many of these dynamic processes, because site-specific information can be obtained for motions that span many time scales, from rapid bond librations (picoseconds) to events that take seconds.

Although I’m sure X-ray crystallography will still be widely used to determine the three dimensional structures of proteins in the future, I think we’ll start to hear more about the utility of NMR spectroscopy, especially since there are a number of NIH-funded structural genomics centers that are using NMR spectroscopy to solve protein structures, there are new labeling methods that may make it possible to use NMR to solve the structures of larger proteins, and there are exciting demonstrations of how solid-state NMR can be used to probe the structure and function of membrane proteins.

NMR can also be used to find important biologically active small-molecules/potential drugs – for example, Oltersdorf et al. used NMR to find and optimize a new anti-cancer compound and Forino et al. used a “fragment-based approach” to find a new inhibitor of the lethal factor metalloproteinase from Bacillus anthracis.

Of course, many of these experiments can’t be done on an aging NMR spectrometer. In a recent Nature paper, Dorothee Kern’s group used a Varian 800-MHz spectrometer to examine the dynamics of the prolyl cistrans isomerase cyclophilin A. 800-MHz spectrometers will need to get a lot cheaper before many laboratories can afford to use them routinely…

Joshua

Joshua Finkelstein (Associate Editor, Nature)


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