AI Article Synopsis
- Calicheamicin γ1(I) (Cal) is a specialized molecule that combines a DNA-binding part and a DNA-cleaving part, making it very effective at cutting DNA at specific locations.
- The study explored how the two different parts—the aryl-tetrasaccharide and the calicheamicinone—contribute to the process of binding to and cleaving DNA.
- Findings showed that these components work together remarkably well, revealing insights that could help in designing better drugs in the future.
Article Abstract
Calicheamicin γ1(I) (Cal) is a unique molecule in which a DNA binding motif (aryl-tetrasaccharide) is linked to a DNA cleaving moiety (calicheamicinone). The hallmark of this natural product rests in the impressive optimization of these two mechanisms leading to a drug that is extremely efficient in cleaving DNA at well-defined sites. However, the relative contributions of these two structurally distinct domains to the overall process have not been fully elucidated yet. Here, we used different experimental approaches to better dissect the role of the aryl-tetrasaccharide and the enediyne moieties in the DNA sequence selective binding step as well as the in the cleavage reaction. Our results highlight the remarkable cooperation of the two components in producing an amazing molecular machine. The herein presented molecular details of this concerted mechanism of action can be further applied to rationally design more druggable compounds.
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| http://dx.doi.org/10.1002/bip.22591 | DOI Listing |
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