Structural Basis of Saccharin Derivative Inhibition of Carbonic Anhydrase IX

This study explores the binding mechanisms of saccharin derivatives with human carbonic anhydrase IX (hCA IX), an antitumor drug target, with the aim of facilitating the design of potent and selective inhibitors. Through the use of crystallographic analysis, we investigate the structures of hCA IX-saccharin derivative complexes, unveiling their unique binding modes that exhibit both similarities to sulfonamides and distinct orientations of the ligand tail. Our comprehensive structural insights provide information regarding the crucial interactions between the ligands and the protein, shedding light on interactions that dictate inhibitor binding and selectivity. Through a comparative analysis of the binding modes observed in hCA II and hCA IX, isoform-specific interactions are identified, offering promising strategies for the development of isoform-selective inhibitors that specifically target tumor-associated hCA IX. The findings of this study significantly deepen our understanding of the binding mechanisms of hCA inhibitors, laying a solid foundation for the rational design of more effective inhibitors. This study investigates the binding mechanisms of saccharin derivatives with human carbonic anhydrase IX (hCA IX), a vital antitumor target. Through crystallographic analysis, distinct binding modes were uncovered, revealing ligand-protein interactions pivotal for inhibitor efficacy and selectivity. This work enhances our understanding of hCA inhibitor binding and informs the rational design of potent agents.image

Automated summary

This study investigates the binding mechanisms between saccharin derivatives and human carbonic anhydrase IX (hCA IX), revealing their unique binding modes and providing insights into the interactions crucial for inhibitor efficacy and selectivity. The findings enhance our understanding of hCA inhibitor binding and inform the rational design of potent agents.