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Molecular dynamics simulations of structural changes during procaspase 3 activation.
Journal article

Molecular dynamics simulations of structural changes during procaspase 3 activation.

  • Piana S Institute of Molecular and Biological Chemistry, Federal Institute of Technology, EPFL, Lausanne, Switzerland.
  • Rothlisberger U
  • 2004-05-18
Published in:
  • Proteins. - 2004
Caspase 3
Caspases
Computer Simulation
Dimerization
Enzyme Activation
Enzyme Precursors
Hydrogen Bonding
Models, Molecular
Molecular Structure
Static Electricity
English 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.
Language
  • English
Open access status
closed
Identifiers
Persistent URL
https://sonar.rero.ch/global/documents/126441
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