1989/05/02 by Linus L. Shen, Lester A. Mitscher, Padam N. Sharma +5 · 4 citations
Biochemistry, Genetics and Molecular Biology · Medicine · Chemistry · #Cancer therapeutics and mechanisms #Drug Transport and Resistance Mechanisms #Synthesis and Biological Evaluation
paper · doi:10.1021/bi00435a039
openalex publication_date 1989/05/02 · openalex created_date 2025/10/10 · openalex updated_date 2026/06/11
We have proposed a cooperative quinolone-DNA binding model for the inhibition of DNA gyrase. The essential feature of the model is that bound gyrase induces a specific quinolone binding site in the relaxed DNA substrate in the presence of ATP. The binding affinity and specificity are derived from two unique and equally important functional features: the specific conformation of the proposed single-stranded DNA pocket induced by the enzyme and the unique self-association phenomenon (from which the cooperativity is derived) of the drug molecules to fit the binding pocket with a high degree of flexibility. Supporting evidence for and implications of this model are provided.