Allosteric inhibition of alpha-thrombin enzymatic activity with ultrasmall gold nanoparticles

Autor(es)

Lira, Andre L. ^[1] ; Ferreira, Rodrigo S. ^[1] ; Torquato, Ricardo J. S. ^[1] ; Oliva, V, Maria Luiza ; Schuck, Peter ^[2] ; Sousa, Alioscka A. ^[3]

Afiliação do(s) autor(es)

^[1] Univ Fed Sao Paulo, Dept Biochem, Sao Paulo, SP - Brazil

^[2] Natl Inst Biomed Imaging & Bioengn, NIH, Bethesda, MD - USA

^[3] Oliva, Maria Luiza, V, Univ Fed Sao Paulo, Dept Biochem, Sao Paulo, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: NANOSCALE ADVANCES; v. 1, n. 1, p. 378-388, JAN 1 2019.
• Citações Web of Science: 4

Resumo

The catalytic activity of enzymes can be regulated by interactions with synthetic nanoparticles (NPs) in a number of ways. To date, however, the potential use of NPs as allosteric effectors has not been investigated in detail. Importantly, targeting allosteric (distal) sites on the enzyme surface could afford unique ways to modulate the activity, allowing for either enzyme activation, partial or full inhibition. Using p-mercaptobenzoic acid-coated ultrasmall gold NPs (AuMBA) and human alpha-thrombin as a model system, here we experimentally tested the hypothesis that enzyme activity could be regulated through ultrasmall NP interactions at allosteric sites. We show that AuMBA interacted selectively and reversibly around two positively charged regions of the thrombin surface (exosites 1 and 2) and away from the active site. NP complexation at the exosites transmitted long-range structural changes over to the active site, altering both substrate binding affinity and catalysis. Significantly, thrombin activity was partially reduced - but not completely inhibited - by interactions with AuMBA. These findings indicate that interactions of proteins with ultrasmall NPs may mimic a typical biomolecular complexation event, and suggest the prospect of using ultrasmall particles as synthetic receptors to allosterically regulate protein function. (AU)

• Processo FAPESP: 13/18481-5 - Interações biológicas de uma biblioteca de nanopartículas de ouro com aplicações na nanomedicina
• Beneficiário: Alioscka Augusto Sousa
• Modalidade de apoio: Auxílio à Pesquisa - Jovens Pesquisadores