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Molecular dynamics simulations of structural changes during procaspase 3 activation
Author(s) -
Piana Stefano,
Rothlisberger Ursula
Publication year - 2004
Publication title -
proteins: structure, function, and bioinformatics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.699
H-Index - 191
eISSN - 1097-0134
pISSN - 0887-3585
DOI - 10.1002/prot.20046
Subject(s) - molecular dynamics , zymogen , dimer , chemistry , biophysics , peptide , selectivity , monomer , substrate (aquarium) , stereochemistry , enzyme , biochemistry , biology , computational chemistry , catalysis , ecology , polymer , organic chemistry
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. Proteins 2004;55:000–000. © 2004 Wiley‐Liss, Inc.