8QHO
Human Carbonic Anhydrase II in complex with 3,4-dihydro-1H-benzo[c][1,2]oxaborinin-1-ol
This is a non-PDB format compatible entry.
Summary for 8QHO
| Entry DOI | 10.2210/pdb8qho/pdb |
| Descriptor | Carbonic anhydrase 2, GLYCEROL, ZINC ION, ... (5 entities in total) |
| Functional Keywords | carbonic anhydrase, inhibitor, metalloenzyme, benzossaborine, boro, lyase |
| Biological source | Homo sapiens (human) |
| Total number of polymer chains | 1 |
| Total formula weight | 29611.54 |
| Authors | Angeli, A.,Ferraroni, M. (deposition date: 2023-09-08, release date: 2024-09-18, Last modification date: 2025-04-02) |
| Primary citation | Giovannuzzi, S.,Nikitjuka, A.,Angeli, A.,Smietana, M.,Massardi, M.L.,Turati, M.,Ronca, R.,Bonardi, A.,Nocentini, A.,Ferraroni, M.,Supuran, C.T.,Winum, J.Y. Benzoxaborinine, New Chemotype for Carbonic Anhydrase Inhibition: Ex Novo Synthesis, Crystallography, In Silico Studies, and Anti-Melanoma Cell Line Activity. J.Med.Chem., 67:18221-18234, 2024 Cited by PubMed Abstract: The benzoxaborinine scaffold, a homologue of benzoxaborole with an additional carbon atom in the boracycle, shows significant potential in developing new therapeutic agents. This study reports the synthesis, inhibition assays against four human carbonic anhydrase (hCA, EC 4.2.1.1) isoforms, and anti-melanoma evaluation of 7-aryl(thio)ureido-substituted benzoxaborinines. Some derivatives, particularly compound , exhibited potent inhibitory activity (below 65 nM) against hCA IX and XII and stronger antiproliferative effects than on human melanoma cells under hypoxia. Crystallographic studies of benzoxaborinine adducts with hCA I and II demonstrated the binding mode of this chemotype, revealing that although both benzoxaborinine and benzoxaborole share a similar zinc-binding mode, the expanded ring in benzoxaborinine led to a different orientation within the active site. These findings suggest that benzoxaborinines hold promise for designing novel carbonic anhydrase inhibitors. PubMed: 39378331DOI: 10.1021/acs.jmedchem.4c01516 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.43 Å) |
Structure validation
Download full validation report
