8Q18
The Crystal Structure of Human Carbonic Anhydrase IX in Complex with Sulfonamide
Summary for 8Q18
| Entry DOI | 10.2210/pdb8q18/pdb |
| Descriptor | Carbonic anhydrase 9, ZINC ION, 1,1,3-tris(oxidanylidene)-2-(2-phenylethyl)-1,2-benzothiazole-6-sulfonamide, ... (5 entities in total) |
| Functional Keywords | ca ix, ca 9, carbonic anhydrase ix, carbonic anhydrase 9, lyase |
| Biological source | Homo sapiens (human) |
| Total number of polymer chains | 4 |
| Total formula weight | 114842.50 |
| Authors | Leitans, J.,Tars, K. (deposition date: 2023-07-31, release date: 2023-11-08, Last modification date: 2024-11-20) |
| Primary citation | Leitans, J.,Kazaks, A.,Bogans, J.,Supuran, C.T.,Akopjana, I.,Ivanova, J.,Zalubovskis, R.,Tars, K. Structural Basis of Saccharin Derivative Inhibition of Carbonic Anhydrase IX. Chemmedchem, 18:e202300454-e202300454, 2023 Cited by PubMed Abstract: 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. PubMed: 37837260DOI: 10.1002/cmdc.202300454 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.13 Å) |
Structure validation
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