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

Author(s)

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

• Document type: Journal article
• Source: Langmuir; v. 36, n. 27, p. 11-pg., 2020-07-14.

Abstract

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)

• FAPESP's process: 16/25535-2 - Biointeractions of gold nanoparticles: influence of macromolecular crowding and soft interactions
• Grantee: Rodrigo da Silva Ferreira
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 19/04372-6 - Interactions of ultrasmall gold nanoparticles with proteins and cells
• Grantee: Alioscka Augusto Sousa
• Support Opportunities: Regular Research Grants