Cooperative Heteroligand Interaction with G-Quadruplexes Shows Evidence of Allosteric Binding.
Journal
Biochemistry
ISSN: 1520-4995
Titre abrégé: Biochemistry
Pays: United States
ID NLM: 0370623
Informations de publication
Date de publication:
22 09 2020
22 09 2020
Historique:
pubmed:
25
8
2020
medline:
17
3
2021
entrez:
25
8
2020
Statut:
ppublish
Résumé
Although allosteric binding of small molecules is commonplace in protein structures, it is rather rare in DNA species such as G-quadruplexes. By using CD melting, here, we found binding of the small-molecule ligands PDS and L2H2-6OTD to the telomeric DNA G-quadruplex was cooperative. Mass spectrometry indicated a 1:1:1 ratio in the ternary binding complex of the telomeric G-quadruplex, PDS, and L2H2-6OTD. Compared to the binding of each individual ligand to the G-quadruplex, single-molecule mechanical unfolding assays revealed a significantly decreased dissociation constant when one ligand is evaluated in the presence of another. This demonstrates that cooperative binding of PDS and L2H2-6OTD to the G-quadruplex is allosteric, which is also supported by the mass spectra data that indicated the ejection of coordinated sodium ions upon binding of the heteroligands to the G-quadruplex. The unprecedented observation of the allosteric ligand binding to higher-ordered structures of DNA may help to design more effective ligands to target non-B DNA species involved in many critical cellular processes.
Identifiants
pubmed: 32833433
doi: 10.1021/acs.biochem.0c00351
pmc: PMC7511437
mid: NIHMS1623085
doi:
Substances chimiques
Aminoquinolines
0
Ligands
0
Oxazoles
0
Picolinic Acids
0
pyridostatin
0
telomestatin
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
3438-3446Subventions
Organisme : NCI NIH HHS
ID : R01 CA236350
Pays : United States
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