Regulation of Thrombin Activity with Ultrasmall Nanoparticles: Effects of Surface Chemistry

Autor(es)

Lira, Andre L. ; Ferreira, Rodrigo S. ; Oliva, Maria Luiza, V ; Sousa, Alioscka A.

• Tipo de documento: Artigo Científico
• Fonte: Langmuir; v. 36, n. 27, p. 11-pg., 2020-07-14.

Resumo

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. (AU)

• Processo FAPESP: 16/25535-2 - Biointerações de nanopartículas de ouro: influência da aglomeração macromolecular e interações fracas
• Beneficiário: Rodrigo da Silva Ferreira
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 19/04372-6 - Interações de nanopartículas de ouro ultrapequenas com proteínas e células
• Beneficiário: Alioscka Augusto Sousa
• Modalidade de apoio: Auxílio à Pesquisa - Regular