Regulation of Thrombin Activity with Ultrasmall Nanoparticles: Effects of Surface Chemistry
Autor: | Rodrigo da Silva Ferreira, Alioscka A. Sousa, Maria Luiza Vilela Oliva, André L. Lira |
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Rok vydání: | 2020 |
Předmět: |
Allosteric regulation
Metal Nanoparticles Nanoparticle Peptide 02 engineering and technology Ligands 010402 general chemistry 01 natural sciences Nanomaterials Thrombin Allosteric Regulation Electrochemistry medicine General Materials Science Spectroscopy chemistry.chemical_classification Binding Sites Effector Surfaces and Interfaces 021001 nanoscience & nanotechnology Condensed Matter Physics 0104 chemical sciences Enzyme chemistry Colloidal gold Biophysics Gold 0210 nano-technology medicine.drug |
Zdroj: | Langmuir. 36:7991-8001 |
ISSN: | 1520-5827 0743-7463 |
Popis: | Nanomaterials displaying well-tailored sizes and surface chemistries can provide novel ways with which to modulate the structure and function of enzymes. Recently, we showed that gold nanoparticles (AuNPs) in the ultrasmall size regime could perform as allosteric effectors inducing partial inhibition of thrombin activity. We now find that the nature of the AuNP surface chemistry controls the interactions to the anion-binding exosites 1 and 2 on the surface of thrombin, the allosterically induced changes to the active-site conformation, and, by extension, the enzymatic activity. Ultrasmall AuNPs passivated with p-mercaptobenzoic acid ligands (AuMBA) and a peptide-based (Ac-ECYN) biomimetic coat (AuECYN) were utilized in our investigations. Remarkably, we found that while AuMBA binds to exosites 1 and 2, AuECYN interacts primarily with exosite 2. It was further established that AuMBA behaves as a "mild denaturant" of thrombin leading to catalytic dysfunction over time. Conversely, AuECYN resembles a proper allosteric effector leading to partial and reversible inhibition of the activity. Collectively, our findings reveal how the distinct binding modes of different AuNP types may uniquely influence thrombin structure and catalysis. The present study further contributes to our understanding of how synthetic nanomaterials could be exploited in the allosteric regulation of enzymes. |
Databáze: | OpenAIRE |
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