期刊
JOURNAL OF MOLECULAR BIOLOGY
卷 434, 期 17, 页码 -出版社
ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
DOI: 10.1016/j.jmb.2022.167531
关键词
allostery; protein dynamics; enzyme regulation; relaxation dispersion; MWC
资金
- Biomedical Technology Research Resource (BTRR)
- NIH [P41GM111135]
- NSF [MCB-1615032]
Conformational fluctuations are important for protein function and allosteric regulation. In this study, NMR experiments were used to investigate the conformational dynamics of ScCM. The results suggest that the two-state MWC model is insufficient to explain the conformational dynamics of ScCM, and tyrosine and tryptophan have different effects on the conformational fluctuations.
Proteins fluctuate between different conformations in solution, and these conformational fluctuations can be important for protein function and allosteric regulation. The chorismate mutase from Saccharomyces cerevisiae (ScCM), a key enzyme in the biosynthesis of aromatic amino acids, is allosterically activated and inhibited by tryptophan and tyrosine, respectively. It was initially proposed that in the absence of effector, ScCM fluctuates between activated R and inhibited T conformations according to the Monod-Wyman-Changeux (MWC) model, although a more complex regulation pattern was later suggested by mutagenesis and kinetic data. Here we used NMR relaxation dispersion experiments to understand the conformational fluctuations on the microsecond-to-millisecond timescale that occur in ScCM. In the absence of allosteric effectors, ScCM did not exclusively exchange between T and R conformations, sug-gesting that the two-state MWC model is insufficient to explain conformational dynamics. Addition of tyr-osine led to the quenching of much of the motion on this timescale, while new motions were identified in the presence of tryptophan. These new motions are consistent with conformational fluctuations into an alternative conformation that may be important for enzyme activity.(c) 2022 Elsevier Ltd. All rights reserved.
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