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

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

Author Lira, André Autor UNIFESP Google Scholar
Ferreira, Rodrigo Autor UNIFESP Google Scholar
Torquato, Ricardo Autor UNIFESP Google Scholar
Oliva, Maria L.V. Autor UNIFESP Google Scholar
Schuck, Peter Google Scholar
Sousa, Alioscka A Autor UNIFESP Google Scholar
Institution Universidade Federal de São Paulo - UNIFESP
Abstract 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 a-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
Keywords Ultrasmall nanoparticles
Enzyme inhibition
Language English
Sponsor Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
Grant number 2013/18481-5
Date 2018-09-24
Publisher Royal Society of Chemistry
Extent 378-388
Origin https://pubs.rsc.org/en/content/articlelanding/2019/na/c8na00081f#!divAbstract
Access rights Open access Open Access
Type Article
URI https://repositorio.unifesp.br/handle/11600/61044

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