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Detection and characterization of a folding intermediate in barnase by NMR


PROTEIN engineering is being developed for mapping the energetics and pathway of protein folding. From kinetic studies on wild-type and mutant proteins, the sequence and energetics of formation of tertiary interactions of side chains can be mapped and the formation of secondary structure inferred1,2. Here we cross-check and complement results from this approach by using a recently developed procedure that traps and characterizes secondary structure in intermediate states using 1H NMR3,4. The refolding of barnase is shown to be a multiphasic process in which the secondary structure in α-helices and β-sheets and some turns is formed more rapidly than is the overall folding.

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Bycroft, M., Matouschek, A., Kellis, J. et al. Detection and characterization of a folding intermediate in barnase by NMR. Nature 346, 488–490 (1990).

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