6WKA
human carbonic anhydrase II bound to an inhibitor modified with azidothymidine
Summary for 6WKA
| Entry DOI | 10.2210/pdb6wka/pdb |
| Descriptor | Carbonic anhydrase 2, ZINC ION, 3'-deoxy-3'-(4-{[(4-sulfamoylphenyl)amino]methyl}-1H-1,2,3-triazol-1-yl)thymidine, ... (4 entities in total) |
| Functional Keywords | human ca ii, inhibitor, click chemistry, azidothymidine, lyase |
| Biological source | Homo sapiens (Human) |
| Total number of polymer chains | 1 |
| Total formula weight | 29831.97 |
| Authors | Peat, T.S. (deposition date: 2020-04-15, release date: 2021-02-24, Last modification date: 2023-10-18) |
| Primary citation | Berrino, E.,Angeli, A.,Zhdanov, D.D.,Kiryukhina, A.P.,Milaneschi, A.,De Luca, A.,Bozdag, M.,Carradori, S.,Selleri, S.,Bartolucci, G.,Peat, T.S.,Ferraroni, M.,Supuran, C.T.,Carta, F. Azidothymidine "Clicked" into 1,2,3-Triazoles: First Report on Carbonic Anhydrase-Telomerase Dual-Hybrid Inhibitors. J.Med.Chem., 63:7392-7409, 2020 Cited by PubMed Abstract: Cancer cells rely on the enzyme telomerase (EC 2.7.7.49) to promote cellular immortality. Telomerase inhibitors (i.e., azidothymidine) can represent promising antitumor agents, although showing high toxicity when administered alone. Better outcomes were observed within a multipharmacological approach instead. In this context, we exploited the validated antitumor targets carbonic anhydrases (CAs; EC 4.2.1.1) IX and XII to attain the first proof of concept on CA-telomerase dual-hybrid inhibitors. Compounds , , , and showed good in vitro inhibition potency against the CAs IX and XII, with values in the low nanomolar range, and strong antitelomerase activity in PC-3 and HT-29 cells (IC values ranging from 5.2 to 9.1 μM). High-resolution X-ray crystallography on selected derivatives in the adduct with hCA II as a model study allowed to determine their binding modes and thus to set the structural determinants necessary for further development of compounds selectively targeting the tumoral cells. PubMed: 32463228DOI: 10.1021/acs.jmedchem.0c00636 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.34 Å) |
Structure validation
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