6RG4
Crystal structure of human Carbonic anhydrase II in complex with (R)-4-(2-benzyl-4-methylpiperazin-1-yl)benzenesulfonamide
Summary for 6RG4
| Entry DOI | 10.2210/pdb6rg4/pdb |
| Descriptor | Carbonic anhydrase 2, ZINC ION, GLYCEROL, ... (5 entities in total) |
| Functional Keywords | lyase |
| Biological source | Homo sapiens (Human) |
| Total number of polymer chains | 1 |
| Total formula weight | 29912.13 |
| Authors | Ferraroni, M.,Angeli, A.,Supuran, C. (deposition date: 2019-04-16, release date: 2020-05-13, Last modification date: 2024-01-24) |
| Primary citation | Chiaramonte, N.,Bua, S.,Angeli, A.,Ferraroni, M.,Picchioni, I.,Bartolucci, G.,Braconi, L.,Dei, S.,Teodori, E.,Supuran, C.T.,Romanelli, M.N. Sulfonamides incorporating piperazine bioisosteres as potent human carbonic anhydrase I, II, IV and IX inhibitors. Bioorg.Chem., 91:103130-103130, 2019 Cited by PubMed Abstract: Starting from the molecular simplification of (R) 4-(3,4-dibenzylpiperazine-1-carbonyl)benzenesulfonamide 9a, a compound endowed with selectivity for human Carbonic Anhydrase (hCA) IV, a series of piperazines and 4-aminopiperidines carrying a 4-sulfamoylbenzamide moiety as Zn-binding group have been designed and tested on human isoforms hCA I, II, IV and IX, using a stopped flow CO hydrase assay. The aim of the work was to derive structure-activity relationships useful for designing isoform selective compounds. These structural modifications changed the selectivity profile of the analogues from hCA IV to hCA I and II, and improved potency. Several of the new compounds showed subnanomolar activity on hCA II. X-ray crystallography of ligand-hCAII complexes was used to compare the binding modes of the new piperazines and the previously synthesized 2-benzyl-piperazine analogues, explaining the inhibition profiles. PubMed: 31374520DOI: 10.1016/j.bioorg.2019.103130 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.25 Å) |
Structure validation
Download full validation report
