Molecular dynamics studies of caspase-3
- Publikationstyp:
- Zeitschriftenaufsatz
- Metadaten:
-
- Autoren
- M Sulpizi
- U Rothlisberger
- P Carloni
- Autoren-URL
- https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=fis-test-1&SrcAuth=WosAPI&KeyUT=WOS:000183123100007&DestLinkType=FullRecord&DestApp=WOS_CPL
- DOI
- 10.1016/S0006-3495(03)75026-7
- Externe Identifier
- Clarivate Analytics Document Solution ID: 682ZZ
- PubMed Identifier: 12668429
- ISSN
- 0006-3495
- Ausgabe der Veröffentlichung
- 4
- Zeitschrift
- BIOPHYSICAL JOURNAL
- Paginierung
- 2207 - 2215
- Datum der Veröffentlichung
- 2003
- Status
- Published
- Titel
- Molecular dynamics studies of caspase-3
- Sub types
- Article
- Ausgabe der Zeitschrift
- 84
Datenquelle: Web of Science (Lite)
- Andere Metadatenquellen:
-
- Autoren
- M Sulpizi
- U Rothlisberger
- P Carloni
- DOI
- 10.1016/s0006-3495(03)75026-7
- ISSN
- 0006-3495
- Ausgabe der Veröffentlichung
- 4
- Zeitschrift
- Biophysical Journal
- Sprache
- en
- Paginierung
- 2207 - 2215
- Datum der Veröffentlichung
- 2003
- Status
- Published
- Herausgeber
- Elsevier BV
- Herausgeber URL
- http://dx.doi.org/10.1016/s0006-3495(03)75026-7
- Datum der Datenerfassung
- 2023
- Titel
- Molecular Dynamics Studies of Caspase-3
- Ausgabe der Zeitschrift
- 84
Datenquelle: Crossref
- Abstract
- Caspase-3 is a fundamental target for pharmaceutical interventions against a variety of diseases involving disregulated apoptosis. The enzyme is active as a dimer with two symmetry-related active sites, each featuring a Cys-His catalytic dyad and a selectivity loop, which recognizes the characteristic DEVD pattern of the substrate. Here, a molecular dynamics study of the enzyme in complex with two pentapeptide substrates DEVDG is presented, which provides a characterization of the dynamic properties of the active form in aqueous solution. The mobility of the substrate and that of the catalytic residues are rather low indicating a distinct preorganization effect of the Michaelis complex. An essential mode analysis permits us to identify coupled motions between the two monomers. In particular, it is found that the motions of the two active site loops are correlated and tend to steer the substrate toward the reactive center, suggesting that dimerization has a distinct effect on the dynamic properties of the active site regions. The selectivity loop of one monomer turns out to be correlated with the N-terminal region of the p12 subunit of the other monomer, an interaction that is also found to play a fundamental role in the electrostatic stabilization of the quaternary structure. To further characterize the specific influence of dimerization on the enzyme essential motions, a molecular dynamics analysis is also performed on the isolated monomer.
- Addresses
- Laboratory of Computational Chemistry and Biochemistry, Federal Institute of Technology (EPFL) CH-1015 Lausanne, Switzerland.
- Autoren
- M Sulpizi
- U Rothlisberger
- P Carloni
- DOI
- 10.1016/s0006-3495(03)75026-7
- eISSN
- 1542-0086
- Externe Identifier
- PubMed Identifier: 12668429
- PubMed Central ID: PMC1302787
- Open access
- false
- ISSN
- 0006-3495
- Ausgabe der Veröffentlichung
- 4
- Zeitschrift
- Biophysical journal
- Schlüsselwörter
- Macromolecular Substances
- Caspases
- Oligopeptides
- Cysteine Proteinase Inhibitors
- Crystallography
- Enzyme Stability
- Binding Sites
- Enzyme Activation
- Protein Conformation
- Protein Structure, Tertiary
- Protein Binding
- Structure-Activity Relationship
- Dimerization
- Motion
- Models, Molecular
- Computer Simulation
- Caspase 3
- Static Electricity
- Caspase Inhibitors
- Sprache
- eng
- Medium
- Paginierung
- 2207 - 2215
- Datum der Veröffentlichung
- 2003
- Status
- Published
- Datum der Datenerfassung
- 2003
- Titel
- Molecular dynamics studies of caspase-3.
- Sub types
- Comparative Study
- research-article
- Evaluation Study
- Journal Article
- Ausgabe der Zeitschrift
- 84
Files
http://www.cell.com/article/S0006349503750267/pdf https://europepmc.org/articles/PMC1302787?pdf=render
Datenquelle: Europe PubMed Central
- Abstract
- Caspase-3 is a fundamental target for pharmaceutical interventions against a variety of diseases involving disregulated apoptosis. The enzyme is active as a dimer with two symmetry-related active sites, each featuring a Cys-His catalytic dyad and a selectivity loop, which recognizes the characteristic DEVD pattern of the substrate. Here, a molecular dynamics study of the enzyme in complex with two pentapeptide substrates DEVDG is presented, which provides a characterization of the dynamic properties of the active form in aqueous solution. The mobility of the substrate and that of the catalytic residues are rather low indicating a distinct preorganization effect of the Michaelis complex. An essential mode analysis permits us to identify coupled motions between the two monomers. In particular, it is found that the motions of the two active site loops are correlated and tend to steer the substrate toward the reactive center, suggesting that dimerization has a distinct effect on the dynamic properties of the active site regions. The selectivity loop of one monomer turns out to be correlated with the N-terminal region of the p12 subunit of the other monomer, an interaction that is also found to play a fundamental role in the electrostatic stabilization of the quaternary structure. To further characterize the specific influence of dimerization on the enzyme essential motions, a molecular dynamics analysis is also performed on the isolated monomer.
- Autoren
- M Sulpizi
- U Rothlisberger
- P Carloni
- Autoren-URL
- https://www.ncbi.nlm.nih.gov/pubmed/12668429
- DOI
- 10.1016/S0006-3495(03)75026-7
- Externe Identifier
- PubMed Central ID: PMC1302787
- ISSN
- 0006-3495
- Ausgabe der Veröffentlichung
- 4
- Zeitschrift
- Biophys J
- Schlüsselwörter
- Binding Sites
- Caspase 3
- Caspase Inhibitors
- Caspases
- Computer Simulation
- Crystallography
- Cysteine Proteinase Inhibitors
- Dimerization
- Enzyme Activation
- Enzyme Stability
- Macromolecular Substances
- Models, Molecular
- Motion
- Oligopeptides
- Protein Binding
- Protein Conformation
- Protein Structure, Tertiary
- Static Electricity
- Structure-Activity Relationship
- Sprache
- eng
- Country
- United States
- Paginierung
- 2207 - 2215
- PII
- S0006-3495(03)75026-7
- Datum der Veröffentlichung
- 2003
- Status
- Published
- Datum, an dem der Datensatz öffentlich gemacht wurde
- 2003
- Titel
- Molecular dynamics studies of caspase-3.
- Sub types
- Comparative Study
- Evaluation Study
- Journal Article
- Ausgabe der Zeitschrift
- 84
Datenquelle: PubMed
- Beziehungen:
-