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231225s2020 xx |||||o 00| ||eng c |
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|a 10.1021/acs.langmuir.0c01352
|2 doi
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|a pubmed24n1038.xml
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|e rakwb
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|a eng
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| 100 |
1 |
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|a Lira, André L
|e verfasserin
|4 aut
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| 245 |
1 |
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|a Regulation of Thrombin Activity with Ultrasmall Nanoparticles
|b Effects of Surface Chemistry
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|c 2020
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|a Text
|b txt
|2 rdacontent
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|a ƒaComputermedien
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|2 rdamedia
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|a ƒa Online-Ressource
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|a Date Completed 21.06.2021
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|a Date Revised 21.06.2021
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|a published: Print-Electronic
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|a Citation Status MEDLINE
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|a 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
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|a Journal Article
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|a Research Support, Non-U.S. Gov't
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|a Ligands
|2 NLM
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|a Gold
|2 NLM
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|a 7440-57-5
|2 NLM
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|a Thrombin
|2 NLM
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|a EC 3.4.21.5
|2 NLM
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|a Ferreira, Rodrigo S
|e verfasserin
|4 aut
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|a Oliva, Maria Luiza V
|e verfasserin
|4 aut
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| 700 |
1 |
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|a Sousa, Alioscka A
|e verfasserin
|4 aut
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| 773 |
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|i Enthalten in
|t Langmuir : the ACS journal of surfaces and colloids
|d 1992
|g 36(2020), 27 vom: 14. Juli, Seite 7991-8001
|w (DE-627)NLM098181009
|x 1520-5827
|7 nnns
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| 773 |
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|g volume:36
|g year:2020
|g number:27
|g day:14
|g month:07
|g pages:7991-8001
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|u http://dx.doi.org/10.1021/acs.langmuir.0c01352
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