6XXT
The crystal structure of hCA II in complex with a 4-(4-aroylpiperazine-1-carbonyl)benzenesulfonamide derivative.
Summary for 6XXT
| Entry DOI | 10.2210/pdb6xxt/pdb |
| Descriptor | Carbonic anhydrase 2, ZINC ION, 4-[4-(phenylcarbonyl)piperazin-1-yl]carbonylbenzenesulfonamide, ... (5 entities in total) |
| Functional Keywords | protein-inhibitor adduct, lyase |
| Biological source | Homo sapiens (Human) |
| Total number of polymer chains | 1 |
| Total formula weight | 30008.24 |
| Authors | Di Fiore, A.,De Simone, G. (deposition date: 2020-01-28, release date: 2020-06-03, Last modification date: 2024-01-24) |
| Primary citation | Mancuso, F.,Di Fiore, A.,De Luca, L.,Angeli, A.,Monti, S.M.,De Simone, G.,Supuran, C.T.,Gitto, R. Looking toward the Rim of the Active Site Cavity of Druggable Human Carbonic Anhydrase Isoforms. Acs Med.Chem.Lett., 11:1000-1005, 2020 Cited by PubMed Abstract: We report the synthesis and biochemical evaluation of a series of substituted 4-(4-aroylpiperazine-1-carbonyl)benzenesulfonamides (-) developed as inhibitors of druggable carbonic anhydrase (CA) isoforms, as tools for the identification of new therapeutics. X-ray crystallography confirmed that this class of benzenesulfonamides binds CAs through the canonical anchoring of the benzenesulfonamide moiety to the metal ion and a recognition of the middle/top area of the active site cavity. Compound (R = 2-Cl) demonstrated relevant selectivity toward brain-expressed hCA VII. The best balancing in binding affinity and selectivity toward tumor-expressed hCA IX/hCA XII over ubiquitous hCA I/hCA II was found for inhibitor (R = 3-NO). Notably (R = 2-F) proved to be the most efficacious inhibitor of hCA XII for which computational studies elucidated the CA recognition process. PubMed: 32435417DOI: 10.1021/acsmedchemlett.0c00062 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.05 Å) |
Structure validation
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