8ROU
Human Carbonic Anhydrase II in complex with biguanide derivative inhibitor 1-carbamimidamido-N-[(4 sulfamoylphenyl)methyl]methanimidamide
This is a non-PDB format compatible entry.
Summary for 8ROU
| Entry DOI | 10.2210/pdb8rou/pdb |
| Descriptor | Carbonic anhydrase 2, ZINC ION, 1-carbamimidoyl-3-[(4-sulfamoylphenyl)methyl]guanidine, ... (6 entities in total) |
| Functional Keywords | metalloenzyme, lyase, inhibitor |
| Biological source | Homo sapiens (human) |
| Total number of polymer chains | 1 |
| Total formula weight | 30497.81 |
| Authors | Baroni, C.,Ferraroni, M. (deposition date: 2024-01-12, release date: 2025-01-29, Last modification date: 2026-02-11) |
| Primary citation | Baroni, C.,Bozdag, M.,Renzi, G.,De Luca, V.,Capasso, C.,Bazzicalupi, C.,Selleri, S.,Ferraroni, M.,Carta, F.,Supuran, C.T. X-ray crystallographic and kinetic studies of biguanide containing aryl sulfonamides as carbonic anhydrase inhibitors. Rsc Med Chem, 16:1633-1640, 2025 Cited by PubMed Abstract: Here, we report a small series of dual-targeting compounds that combine the prototypical carbonic anhydrase (CA) zinc-binding sulfonamide moiety with the biguanide group of metformin, an emerging anticancer drug. The compounds reported similar inhibition profiles on a panel of physiologically relevant human (h)CAs, with marked selectivity for the cancer related IX and XII isoforms. The binding modes of representative inhibitors 5b and 5c within the active site of the hCA isoforms II and XII-mimic were assessed by X-ray crystallography, thus allowing us to clarify molecular features that may be useful for the design of more specific and potent inhibitors. For instance, we identified a mutation in the hCA XII-mimic which was found responsible for the selectivity of the ligands toward the tumor associated isoform. Interestingly, in the hCA II/5c complex, a second inhibitor molecule was bound to the catalytic cleft, probably affecting the inhibition properties of the canonical zinc-bound inhibitor. PubMed: 39935522DOI: 10.1039/d4md01018c PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.08 Å) |
Structure validation
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