Graphene quantum dots blocking the channel egresses of cytochrome P450 enzyme (CYP3A4) reveals potential toxicity.
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
30 Nov 2023
30 Nov 2023
Historique:
received:
20
10
2023
accepted:
28
11
2023
medline:
4
12
2023
pubmed:
1
12
2023
entrez:
30
11
2023
Statut:
epublish
Résumé
Graphene quantum dots (GQDs) have garnered significant attention, particularly in the biomedical domain. However, extensive research reveals a dichotomy concerning the potential toxicity of GQDs, presenting contrasting outcomes. Therefore, a comprehensive understanding of GQD biosafety necessitates a detailed supplementation of their toxicity profile. In this study, employing a molecular dynamics (MD) simulation approach, we systematically investigate the potential toxicity of GQDs on the CYP3A4 enzyme. We construct two distinct simulation systems, wherein a CYP3A4 protein is enveloped by either GQDs or GOQDs (graphene oxide quantum dots). Our results elucidate that GQDs come into direct contact with the bottleneck residues of Channels 2a and 2b of CYP3A4. Furthermore, GQDs entirely cover the exits of Channels 2a and 2b, implying a significant hindrance posed by GQDs to these channels and consequently leading to toxicity towards CYP3A4. In-depth analysis reveals that the adsorption of GQDs to the exits of Channels 2a and 2b is driven by a synergistic interplay of hydrophobic and van der Waals (vdW) interactions. In contrast, GOQDs only partially obstruct Channel 1 of CYP3A4, indicating a weaker influence on CYP3A4 compared to GQDs. Our findings underscore the potential deleterious impact of GQDs on the CYP3A4 enzyme, providing crucial molecular insights into GQD toxicology.
Identifiants
pubmed: 38036640
doi: 10.1038/s41598-023-48618-z
pii: 10.1038/s41598-023-48618-z
pmc: PMC10689800
doi:
Substances chimiques
Graphite
7782-42-5
Cytochrome P-450 CYP3A
EC 1.14.14.1
Cytochrome P-450 Enzyme System
9035-51-2
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
21091Subventions
Organisme : Basic and Applied Basic Research Foundation of Guangdong Province
ID : 2022A1515220075
Organisme : National Natural Science Foundation of China
ID : 12104394
Informations de copyright
© 2023. The Author(s).
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