Conformational Dynamics of the Dengue Virus Protease Revealed by Fluorescence Correlation and Single-Molecule FRET Studies
- Publikationstyp:
- Zeitschriftenaufsatz
- Metadaten:
-
- Autoren
- Christian Goetz
- Gerald Hinze
- Andrea Gellert
- Hannah Maus
- Franziska von Hammerstein
- Stefan J Hammerschmidt
- Luca M Lauth
- Ute A Hellmich
- Tanja Schirmeister
- Thomas Basche
- Autoren-URL
- https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=fis-test-1&SrcAuth=WosAPI&KeyUT=WOS:000670636400010&DestLinkType=FullRecord&DestApp=WOS_CPL
- DOI
- 10.1021/acs.jpcb.1c01797
- eISSN
- 1520-5207
- Externe Identifier
- Clarivate Analytics Document Solution ID: TF3SG
- PubMed Identifier: 34137269
- ISSN
- 1520-6106
- Ausgabe der Veröffentlichung
- 25
- Zeitschrift
- JOURNAL OF PHYSICAL CHEMISTRY B
- Paginierung
- 6837 - 6846
- Datum der Veröffentlichung
- 2021
- Status
- Published
- Titel
- Conformational Dynamics of the Dengue Virus Protease Revealed by Fluorescence Correlation and Single-Molecule FRET Studies
- Sub types
- Article
- Ausgabe der Zeitschrift
- 125
Datenquelle: Web of Science (Lite)
- Andere Metadatenquellen:
-
- Autoren
- Christian Götz
- Gerald Hinze
- Andrea Gellert
- Hannah Maus
- Franziska von Hammerstein
- Stefan J Hammerschmidt
- Luca M Lauth
- Ute A Hellmich
- Tanja Schirmeister
- Thomas Basché
- DOI
- 10.1021/acs.jpcb.1c01797
- eISSN
- 1520-5207
- ISSN
- 1520-6106
- Ausgabe der Veröffentlichung
- 25
- Zeitschrift
- The Journal of Physical Chemistry B
- Sprache
- en
- Online publication date
- 2021
- Paginierung
- 6837 - 6846
- Datum der Veröffentlichung
- 2021
- Status
- Published
- Herausgeber
- American Chemical Society (ACS)
- Herausgeber URL
- http://dx.doi.org/10.1021/acs.jpcb.1c01797
- Datum der Datenerfassung
- 2023
- Titel
- Conformational Dynamics of the Dengue Virus Protease Revealed by Fluorescence Correlation and Single-Molecule FRET Studies
- Ausgabe der Zeitschrift
- 125
Datenquelle: Crossref
- Abstract
- The dengue virus protease (DENV-PR) represents an attractive target for counteracting DENV infections. It is generally assumed that DENV-PR can exist in an open and a closed conformation and that active site directed ligands stabilize the closed state. While crystal structures of both the open and the closed conformation were successfully resolved, information about the prevalence of these conformations in solution remains elusive. Herein, we address the question of whether there is an equilibrium between different conformations in solution which can be influenced by addition of a competitive inhibitor. To this end, DENV-PR was statistically labeled by two dye molecules constituting a FRET (fluorescence resonance energy transfer) couple. Fluorescence correlation spectroscopy and photon-burst detection were employed to examine FRET pair labeled DENV-PRs freely diffusing in solution. The measurements were performed with two double mutants and with two dye couples. The data provide strong evidence that an equilibrium of at least two conformations of DENV-PR exists in solution. The competitive inhibitor stabilizes the closed state. Because the open and closed conformations appear to coexist in solution, our results support the picture of a conformational selection rather than that of an induced fit mechanism with respect to the inhibitor-induced formation of the closed state.
- Addresses
- Department of Chemistry, Johannes Gutenberg-University Mainz, Mainz, Germany.
- Autoren
- Christian Götz
- Gerald Hinze
- Andrea Gellert
- Hannah Maus
- Franziska von Hammerstein
- Stefan J Hammerschmidt
- Luca M Lauth
- Ute A Hellmich
- Tanja Schirmeister
- Thomas Basché
- DOI
- 10.1021/acs.jpcb.1c01797
- eISSN
- 1520-5207
- Externe Identifier
- PubMed Identifier: 34137269
- Funding acknowledgements
- Deutsche Forschungsgemeinschaft: EXC 2051/390713860
- Open access
- false
- ISSN
- 1520-6106
- Ausgabe der Veröffentlichung
- 25
- Zeitschrift
- The journal of physical chemistry. B
- Schlüsselwörter
- Dengue Virus
- Serine Endopeptidases
- Viral Nonstructural Proteins
- Fluorescence Resonance Energy Transfer
- Catalytic Domain
- Sprache
- eng
- Medium
- Print-Electronic
- Online publication date
- 2021
- Paginierung
- 6837 - 6846
- Datum der Veröffentlichung
- 2021
- Status
- Published
- Datum der Datenerfassung
- 2021
- Titel
- Conformational Dynamics of the Dengue Virus Protease Revealed by Fluorescence Correlation and Single-Molecule FRET Studies.
- Sub types
- Research Support, Non-U.S. Gov't
- Journal Article
- Ausgabe der Zeitschrift
- 125
Datenquelle: Europe PubMed Central
- Abstract
- The dengue virus protease (DENV-PR) represents an attractive target for counteracting DENV infections. It is generally assumed that DENV-PR can exist in an open and a closed conformation and that active site directed ligands stabilize the closed state. While crystal structures of both the open and the closed conformation were successfully resolved, information about the prevalence of these conformations in solution remains elusive. Herein, we address the question of whether there is an equilibrium between different conformations in solution which can be influenced by addition of a competitive inhibitor. To this end, DENV-PR was statistically labeled by two dye molecules constituting a FRET (fluorescence resonance energy transfer) couple. Fluorescence correlation spectroscopy and photon-burst detection were employed to examine FRET pair labeled DENV-PRs freely diffusing in solution. The measurements were performed with two double mutants and with two dye couples. The data provide strong evidence that an equilibrium of at least two conformations of DENV-PR exists in solution. The competitive inhibitor stabilizes the closed state. Because the open and closed conformations appear to coexist in solution, our results support the picture of a conformational selection rather than that of an induced fit mechanism with respect to the inhibitor-induced formation of the closed state.
- Autoren
- Christian Götz
- Gerald Hinze
- Andrea Gellert
- Hannah Maus
- Franziska von Hammerstein
- Stefan J Hammerschmidt
- Luca M Lauth
- Ute A Hellmich
- Tanja Schirmeister
- Thomas Basché
- Autoren-URL
- https://www.ncbi.nlm.nih.gov/pubmed/34137269
- DOI
- 10.1021/acs.jpcb.1c01797
- eISSN
- 1520-5207
- Ausgabe der Veröffentlichung
- 25
- Zeitschrift
- J Phys Chem B
- Schlüsselwörter
- Catalytic Domain
- Dengue Virus
- Fluorescence Resonance Energy Transfer
- Serine Endopeptidases
- Viral Nonstructural Proteins
- Sprache
- eng
- Country
- United States
- Paginierung
- 6837 - 6846
- Datum der Veröffentlichung
- 2021
- Status
- Published
- Datum, an dem der Datensatz öffentlich gemacht wurde
- 2021
- Titel
- Conformational Dynamics of the Dengue Virus Protease Revealed by Fluorescence Correlation and Single-Molecule FRET Studies.
- Sub types
- Journal Article
- Research Support, Non-U.S. Gov't
- Ausgabe der Zeitschrift
- 125
Datenquelle: PubMed
- Beziehungen:
- Eigentum von