8GP7

Structure of Trioxacarcin A covalently bound to RET G4-DNA

Summary for 8GP7

• Entry DOI: 10.2210/pdb8gp7/pdb
• Descriptor: DNA (5'-D(*GP*GP*GP*GP*CP*GP*GP*GP*GP*CP*GP*GP*GP*GP*CP*GP*GP*GP*GP*T)-3'), Trioxacarcin A, bound form (2 entities in total)
• Functional Keywords: g-quadruplex, dna
• Biological source: synthetic construct
• Total number of polymer chains: 1
• Total formula weight: 7272.94

Authors

Yin, S.,Cao, C. (deposition date: 2022-08-25, release date: 2023-09-06, Last modification date: 2024-05-15)

Primary citation

Yin, S.,Lan, W.,Hou, X.,Liu, Z.,Xue, H.,Wang, C.,Tang, G.L.,Cao, C.
Trioxacarcin A Interactions with G-Quadruplex DNA Reveal Its Potential New Targets as an Anticancer Agent.
J.Med.Chem., 66:6798-6810, 2023

PubMed Abstract: Trioxacarcin (TXN) A was reported to be an anticancer agent through alkylation of dsDNA. G-quadruplex DNA (G4-DNA) is frequently formed in the promoter regions of oncogenes and the ends of telomerase genes, considered as promising drug targets for anticancer therapy. There are no reports about TXN A interactions with G4-DNA. Here, we tested TXN A's interactions with several G4-DNA oligos with parallel, antiparallel, or hybrid folding, respectively. We demonstrated that TXN A preferred to alkylate one flexible guanine in the loops of parallel G4-DNA. The position of the alkylated guanine is in favor of interactions of G4-DNA with TXN A. The structure of TXN A covalently bound RET G4-DNA indicated that TXN A alkylation on RET G4-DNA stabilizes the G4-DNA conformation. These studies opened a new window of how TXN A interacted with G4-DNA, which might hint a new mode of its function as an anticancer agent.

PubMed: 37154782
DOI: 10.1021/acs.jmedchem.3c00178

Experimental method

SOLUTION NMR