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Effects of Calcium Binding on Structure and Autolysis Regulation in Trypsins. A Molecular Dynamics Investigation

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    Effects of Calcium Binding on Structure and Autolysis Regulation in Trypsins. A Molecular Dynamics Investigation
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    Department of Biotechnology and Biosciences, University of Milano-Bicocca, P.za della Scienza 2, 20126 Milan, Italy
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    Journal of Chemical Theory and Computation

    Cite this: J. Chem. Theory Comput. 2005, 1, 6, 1286–1297
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    https://doi.org/10.1021/ct050092o
    Published October 5, 2005
    Copyright © 2005 American Chemical Society
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    Abstract

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    The calcium ion was proposed to be involved in protein structure stabilization against thermal and proteolytic degradation, such as autolysis phenomena, in trypsin-like serine proteases. However, molecular details related to the role played by the metal ion are still largely unknown. Several molecular dynamics simulations of 6 ns have been used to investigate the dynamic behavior of bovine and salmon trypsins in calcium-bound and calcium-free forms, with the aim of evaluating the role of the calcium ion in trypsin three-dimensional structure and autoproteolysis propensity. It turned out that the calcium-free trypsins are characterized by a more flexible structure, revealing structure−function relationships connecting Ca2+ binding and autoproteolysis propensity. In particular, the removal of Ca2+ not only increases the flexibility of regions around its binding site, in the N-terminal domain, but also leads to channeling of the fluctuations to remote sites in the C-terminal domain, possibly involving the interdomain loop. Two primary autolysis sites are strongly influenced by calcium binding (R117 and K188) in bovine trypsin, whereas Ca2+ plays a less crucial role in salmon trypsin.

    Copyright © 2005 American Chemical Society

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    Cite this: J. Chem. Theory Comput. 2005, 1, 6, 1286–1297
    Click to copy citationCitation copied!
    https://doi.org/10.1021/ct050092o
    Published October 5, 2005
    Copyright © 2005 American Chemical Society
    Request reuse permissions

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