Molecular dynamics simulations of structural changes during procaspase 3 activation.

Stefano Piana; Ursula Rothlisberger

doi:10.1002/prot.20046

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PubMed · 15146491

Molecular dynamics simulations of structural changes during procaspase 3 activation.

Stefano Piana·Ursula Rothlisberger

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Abstract

Molecular dynamics (MD) simulations of the structural rearrangements on the pathway leading to procaspase 3 activation are presented. A retrostructural approach is used to build procaspase 3 from mature caspase 3. The peptide bond that is cleaved during enzyme maturation is gradually reformed during the MD simulation and the most relevant structural changes that occur as a consequence are analyzed. The main structural features that characterize this procaspase 3 model are compared with the available X-ray structure of procaspase 7 as the only zymogen structure that has been crystallised so far. The MD simulations indicate that in the free caspase 3, the flexible selectivity loop is already preorganized to accomodate the substrate. Such a preorganization is not present in either monomeric caspase 3 or in the procaspase 3 dimer, indicating that the structure of the selectivity loop is highly sensitive to perturbations.

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Caspase 3 Caspases Computer Simulation Dimerization Enzyme Activation Enzyme Precursors Hydrogen Bonding Models, Molecular Molecular Structure Static Electricity Journal Article Research Support, Non-U.S. Gov't

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Stefano Piana, Ursula Rothlisberger. 2004-06-01. Molecular dynamics simulations of structural changes during procaspase 3 activation.. https://doi.org/10.1002/prot.20046

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