Conformational Selection and Induced Fit: The Behavior of Two Homologous Proteases
- Publikationstyp:
- Zeitschriftenaufsatz
- Metadaten:
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- Abstract
- <jats:title>Abstract</jats:title><jats:p>Protein‐ligand interactions are crucial for many cellular processes, with details of the binding mechanism being discussed as essential for biological functions. Interestingly, protein binding often involves conformational changes between two or more states, whereby different binding mechanisms are possible even with a simple two‐state description. Two models are widely used to portray protein‐ligand interactions: Induced fit and conformational selection. However, distinguishing them experimentally is challenging. Single‐molecule Förster resonance energy transfer (smFRET) has emerged as a powerful tool to resolve structural dynamics at the level of single proteins. Here, we investigated immobilized Zika virus (ZIKV) and dengue virus (DENV2) NS2B‐NS3 proteases using smFRET to compare their conformational changes upon binding to competitive small molecule inhibitors. The analysis of the smFRET data allowed us to distinguish between induced fit and conformational selection models and assign the binding mechanism from the kinetic parameters obtained. Although DENV and ZIKV protease are proteins with high structural similarities, our results reveal that they have opposite binding mechanisms for competitive ligands. While the protein‐ligand interaction in the ZIKV protease follows an induced fit mechanism, the DENV protease follows the conformational selection mechanism.</jats:p>
- Autoren
- Hannah Maus
- Gerald Hinze
- Stefan J Hammerschmidt
- Tanja Schirmeister
- Thomas Basché
- DOI
- 10.1002/ceur.202300060
- eISSN
- 2751-4765
- ISSN
- 2751-4765
- Ausgabe der Veröffentlichung
- 3
- Zeitschrift
- ChemistryEurope
- Sprache
- en
- Online publication date
- 2023
- Datum der Veröffentlichung
- 2023
- Status
- Published
- Herausgeber
- Wiley
- Herausgeber URL
- http://dx.doi.org/10.1002/ceur.202300060
- Datum der Datenerfassung
- 2023
- Titel
- Conformational Selection and Induced Fit: The Behavior of Two Homologous Proteases
- Ausgabe der Zeitschrift
- 1
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