7NH6
Crystal structure of human carbonic anhydrase II with 3-(3-((1-(2-(hydroxymethyl)-5-(5-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)tetrahydrofuran-3-yl)-1H-1,2,3-triazol-4-yl)methyl)ureido)benzenesulfonamide
This is a non-PDB format compatible entry.
Summary for 7NH6
| Entry DOI | 10.2210/pdb7nh6/pdb |
| Descriptor | Carbonic anhydrase 2, ZINC ION, GLYCEROL, ... (5 entities in total) |
| Functional Keywords | carbonic anhydrase ii, inhibitor, metalloenzyme, sulfonamide, lyase |
| Biological source | Homo sapiens (Human) |
| Total number of polymer chains | 1 |
| Total formula weight | 29967.08 |
| Authors | Angeli, A.,Ferraroni, M. (deposition date: 2021-02-10, release date: 2022-02-23, Last modification date: 2024-01-31) |
| Primary citation | Plyasova, A.A.,Berrino, E.,Khan, I.I.,Veselovsky, A.V.,Pokrovsky, V.S.,Angeli, A.,Ferraroni, M.,Supuran, C.T.,Pokrovskaya, M.V.,Alexandrova, S.S.,Gladilina, Y.A.,Sokolov, N.N.,Hilal, A.,Carta, F.,Zhdanov, D.D. Mechanisms of the Antiproliferative and Antitumor Activity of Novel Telomerase-Carbonic Anhydrase Dual-Hybrid Inhibitors. J.Med.Chem., 64:11432-11444, 2021 Cited by PubMed Abstract: Human (h) telomerase (TL; EC 2.7.7.49) plays a key role in sustaining cancer cells by means of elongating telomeric repeats at the 3' ends of chromosomes. Since TL-inhibitor (TI) stand-alone cancer therapy has been proven to be remarkably challenging, a polypharmacological approach represents a valid alternative. Here we consider a series of compounds able to inhibit both hTL and the tumor-associated carbonic anhydrases (CAs; EC 4.2.1.1) IX and XII. Compounds and suppressed hTL activity in both cell lysates and human colon cancer cell lines, and prolonged incubation with either or resulted in telomere shortening, cell cycle arrest, replicative senescence, and apoptosis. Enzyme kinetics showed that and are mixed-type inhibitors of the binding of DNA primers and deoxynucleoside triphosphate (dNTP) to the TL catalytic subunit hTERT, which is in agreement with docking experiments. Compound showed antitumor activity in Colo-205 mouse xenografts and suppressed telomerase activity by telomere reduction. PubMed: 34283610DOI: 10.1021/acs.jmedchem.1c00756 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.28 Å) |
Structure validation
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