The effects of allosteric and competitive inhibitors on ZIKV protease conformational dynamics explored through smFRET, nanoDSF, DSF, and 19F NMR

Publikationstyp:
Zeitschriftenaufsatz
Metadaten:
Autoren
  • Hannah Maus
  • Stefan J Hammerschmidt
  • Gerald Hinze
  • Fabian Barthels
  • Victor H Perez Carrillo
  • Ute A Hellmich
  • Thomas Basche
  • Tanja Schirmeister
Autoren-URL
https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=fis-test-1&SrcAuth=WosAPI&KeyUT=WOS:001037250700001&DestLinkType=FullRecord&DestApp=WOS_CPL
DOI
10.1016/j.ejmech.2023.115573
eISSN
1768-3254
Externe Identifier
  • Clarivate Analytics Document Solution ID: N5EU9
  • PubMed Identifier: 37379675
ISSN
0223-5234
Zeitschrift
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
Schlüsselwörter
  • ZIKV NS2B-NS3 protease
  • Allosteric
  • competitive inhibition
  • Conformational dynamics
  • smFRET
  • (Nano)DSF
Artikelnummer
ARTN 115573
Datum der Veröffentlichung
2023
Status
Published
Titel
The effects of allosteric and competitive inhibitors on ZIKV protease conformational dynamics explored through smFRET, nanoDSF, DSF, and 19F NMR
Sub types
  • Article
Ausgabe der Zeitschrift
258

Datenquelle: Web of Science (Lite)

Andere Metadatenquellen:
Autoren
  • Hannah Maus
  • Stefan J Hammerschmidt
  • Gerald Hinze
  • Fabian Barthels
  • Victor H Pérez Carrillo
  • Ute A Hellmich
  • Thomas Basché
  • Tanja Schirmeister
DOI
10.1016/j.ejmech.2023.115573
ISSN
0223-5234
Zeitschrift
European Journal of Medicinal Chemistry
Sprache
en
Artikelnummer
115573
Paginierung
115573 - 115573
Datum der Veröffentlichung
2023
Status
Published
Herausgeber
Elsevier BV
Herausgeber URL
http://dx.doi.org/10.1016/j.ejmech.2023.115573
Datum der Datenerfassung
2023
Titel
The effects of allosteric and competitive inhibitors on ZIKV protease conformational dynamics explored through smFRET, nanoDSF, DSF, and 19F NMR
Ausgabe der Zeitschrift
258

Datenquelle: Crossref

Abstract
Zika and dengue viruses cause mosquito-borne diseases of high epidemic relevance. The viral NS2B-NS3 proteases play crucial roles in the pathogen replication cycle and are validated drug targets. They can adopt at least two conformations depending on the position of the NS2B cofactor. Recently, we reported ligand-induced conformational changes of dengue virus NS2B-NS3 protease by single-molecule Förster resonance energy transfer (smFRET). Here, we investigated the conformational dynamics of the homologous Zika virus protease through an integrated methodological approach combining smFRET, thermal shift assays (DSF and nanoDSF) and <sup>19</sup>F NMR spectroscopy. Our results show that allosteric inhibitors favor the open conformation and competitive inhibitors stabilize the closed conformation of the Zika virus protease.
Addresses
  • Institute of Pharmaceutical and Biomedical Sciences (IPBW), Johannes Gutenberg-University, Mainz, Germany.
Autoren
  • Hannah Maus
  • Stefan J Hammerschmidt
  • Gerald Hinze
  • Fabian Barthels
  • Victor H Pérez Carrillo
  • Ute A Hellmich
  • Thomas Basché
  • Tanja Schirmeister
DOI
10.1016/j.ejmech.2023.115573
eISSN
1768-3254
Externe Identifier
  • PubMed Identifier: 37379675
Open access
false
ISSN
0223-5234
Zeitschrift
European journal of medicinal chemistry
Schlüsselwörter
  • Animals
  • Peptide Hydrolases
  • Serine Endopeptidases
  • Viral Nonstructural Proteins
  • Protease Inhibitors
  • Fluorescence Resonance Energy Transfer
  • Magnetic Resonance Spectroscopy
  • Protein Conformation
  • Zika Virus
  • Zika Virus Infection
Sprache
eng
Medium
Print-Electronic
Online publication date
2023
Paginierung
115573
Datum der Veröffentlichung
2023
Status
Published
Datum der Datenerfassung
2023
Titel
The effects of allosteric and competitive inhibitors on ZIKV protease conformational dynamics explored through smFRET, nanoDSF, DSF, and <sup>19</sup>F NMR.
Sub types
  • Journal Article
Ausgabe der Zeitschrift
258

Datenquelle: Europe PubMed Central

Abstract
Zika and dengue viruses cause mosquito-borne diseases of high epidemic relevance. The viral NS2B-NS3 proteases play crucial roles in the pathogen replication cycle and are validated drug targets. They can adopt at least two conformations depending on the position of the NS2B cofactor. Recently, we reported ligand-induced conformational changes of dengue virus NS2B-NS3 protease by single-molecule Förster resonance energy transfer (smFRET). Here, we investigated the conformational dynamics of the homologous Zika virus protease through an integrated methodological approach combining smFRET, thermal shift assays (DSF and nanoDSF) and 19F NMR spectroscopy. Our results show that allosteric inhibitors favor the open conformation and competitive inhibitors stabilize the closed conformation of the Zika virus protease.
Date of acceptance
2023
Autoren
  • Hannah Maus
  • Stefan J Hammerschmidt
  • Gerald Hinze
  • Fabian Barthels
  • Victor H Pérez Carrillo
  • Ute A Hellmich
  • Thomas Basché
  • Tanja Schirmeister
Autoren-URL
https://www.ncbi.nlm.nih.gov/pubmed/37379675
DOI
10.1016/j.ejmech.2023.115573
eISSN
1768-3254
Zeitschrift
Eur J Med Chem
Schlüsselwörter
  • (19)F NMR
  • (Nano)DSF
  • Allosteric/competitive inhibition
  • Conformational dynamics
  • ZIKV NS2B-NS3 protease
  • smFRET
  • Animals
  • Zika Virus
  • Zika Virus Infection
  • Peptide Hydrolases
  • Fluorescence Resonance Energy Transfer
  • Serine Endopeptidases
  • Viral Nonstructural Proteins
  • Protein Conformation
  • Magnetic Resonance Spectroscopy
  • Protease Inhibitors
Sprache
eng
Country
France
Paginierung
115573
PII
S0223-5234(23)00539-1
Datum der Veröffentlichung
2023
Status
Published
Datum, an dem der Datensatz öffentlich gemacht wurde
2023
Titel
The effects of allosteric and competitive inhibitors on ZIKV protease conformational dynamics explored through smFRET, nanoDSF, DSF, and 19F NMR.
Sub types
  • Journal Article
Ausgabe der Zeitschrift
258

Datenquelle: PubMed

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