3IGP
Structure of inhibitor binding to Carbonic Anhydrase II
Summary for 3IGP
| Entry DOI | 10.2210/pdb3igp/pdb |
| Descriptor | Carbonic anhydrase 2, ZINC ION, 6,7-dimethoxy-3,4-dihydroisoquinoline-2(1H)-sulfonamide, ... (5 entities in total) |
| Functional Keywords | carbonic anhydrase inhibitors, isoquinolines, lyase, acetylation, cytoplasm, disease mutation, metal-binding, polymorphism, zinc |
| Biological source | Homo sapiens (human) |
| Total number of polymer chains | 1 |
| Total formula weight | 30083.30 |
| Authors | Gitto, R.,Agnello, S.,Brynda, J.,Mader, P.,Supuran, C.T.,Chimirri, A. (deposition date: 2009-07-28, release date: 2010-03-09, Last modification date: 2023-11-01) |
| Primary citation | Gitto, R.,Agnello, S.,Ferro, S.,De Luca, L.,Vullo, D.,Brynda, J.,Mader, P.,Supuran, C.T.,Chimirri, A. Identification of 3,4-Dihydroisoquinoline-2(1H)-sulfonamides as Potent Carbonic Anhydrase Inhibitors: Synthesis, Biological Evaluation, and Enzyme-Ligand X-ray Studies. J.Med.Chem., 2010 Cited by PubMed Abstract: Following previous studies we herein report the exploration of the carbonic anhydrase (CA, EC 4.2.1.1) inhibitory effects and enzyme selectivity of a small class of 1-(cyclo)alkylisoquinolines containing a sulfonamide function considered a key feature for inhibiting CA. The results of enzymatic assays against human (h) CA isoforms, hCA I and hCA II (cytosolic, ubiquitous enzymes), hCA IX (transmembrane, tumor-associated), and hCA XIV (transmembrane), suggested that the presence of C-1 small substituents on isoquinoline scaffold controls both inhibitory potency and selectivity. Some derivatives showed potent hCA IX and hCA XIV inhibitory effects at nanomolar concentrations as well as low affinity for the ubiquitous hCA II. Moreover, we report the X-ray crystal structure of one of these derivatives in complex with dominant human isoform II, thus confirming the sulfonamide--zinc interactions. Finally, the results of docking experiments suggested the hypothetic interactions in the catalytic binding site for the most active and selective hCA IX and hCA XIV inhibitor. PubMed: 20170095DOI: 10.1021/jm9014026 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.65 Å) |
Structure validation
Download full validation report
