5E2K
Crystal structure of human carbonic anhydrase II in complex with the 4-(3-aminophenyl)benzenesulfonamide inhibitor
Summary for 5E2K
| Entry DOI | 10.2210/pdb5e2k/pdb |
| Descriptor | Carbonic anhydrase 2, ZINC ION, 3'-aminobiphenyl-4-sulfonamide, ... (5 entities in total) |
| Functional Keywords | lyase |
| Biological source | Homo sapiens (Human) |
| Cellular location | Cytoplasm : P00918 |
| Total number of polymer chains | 1 |
| Total formula weight | 29586.75 |
| Authors | Ferraroni, M.,Supuran, C.T. (deposition date: 2015-10-01, release date: 2016-01-20, Last modification date: 2024-01-10) |
| Primary citation | Cornelio, B.,Laronze-Cochard, M.,Ceruso, M.,Ferraroni, M.,Rance, G.A.,Carta, F.,Khlobystov, A.N.,Fontana, A.,Supuran, C.T.,Sapi, J. 4-Arylbenzenesulfonamides as Human Carbonic Anhydrase Inhibitors (hCAIs): Synthesis by Pd Nanocatalyst-Mediated Suzuki-Miyaura Reaction, Enzyme Inhibition, and X-ray Crystallographic Studies. J.Med.Chem., 59:721-732, 2016 Cited by PubMed Abstract: Benzenesulfonamides bearing various substituted (hetero)aryl rings in the para-position were prepared by palladium nanoparticle-catalyzed Suzuki-Miyaura cross-coupling reactions and evaluated as human carbonic anhydrase (hCA, EC 4.2.1.1) inhibitors against isoforms hCA I, II, IX, and XII. Most of the prepared sulfonamides showed low inhibition against hCA I isoform, whereas the other cytosolic isoenzyme, hCA II, was strongly affected. The major part of these new derivatives acted as potent inhibitors of the tumor-associated isoform hCA XII. An opposite trend was observed for phenyl, naphthyl, and various heteroaryl substituted benzenesulfonamides which displayed subnanomolar hCA IX inhibition while poorly inhibiting the other tumor-associated isoform hCA XII. The inhibition potency and influence of the partially restricted aryl-aryl bond rotation on the activity/selectivity were rationalized by means of X-ray crystallography of the adducts of hCA II with several 4-arylbenzenesulfonamides. PubMed: 26741028DOI: 10.1021/acs.jmedchem.5b01771 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.4 Å) |
Structure validation
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