4KP5
Crystal structure of catalytic domain of human carbonic anhydrase isozyme XII with 2-Chloro-4-[(pyrimidin-2-ylsulfanyl)acetyl]benzenesulfonamide
Summary for 4KP5
| Entry DOI | 10.2210/pdb4kp5/pdb |
| Related | 4KNI 4KNJ 4KNM 4KNN 4KP8 |
| Descriptor | Carbonic anhydrase 12, ZINC ION, 2-chloro-4-[(pyrimidin-2-ylsulfanyl)acetyl]benzenesulfonamide, ... (6 entities in total) |
| Functional Keywords | drug design, carbonic anhydrase, benzenesulfonamide, metal-binding, lyase-lyase inhibitor complex, lyase/lyase inhibitor |
| Biological source | Homo sapiens (human) |
| Cellular location | Membrane; Single-pass type I membrane protein: O43570 |
| Total number of polymer chains | 4 |
| Total formula weight | 121774.61 |
| Authors | Smirnov, A.,Manakova, E.,Grazulis, S. (deposition date: 2013-05-13, release date: 2013-11-06, Last modification date: 2024-11-06) |
| Primary citation | Capkauskaite, E.,Zubriene, A.,Smirnov, A.,Torresan, J.,Kisonaite, M.,Kazokaite, J.,Gylyte, J.,Michailoviene, V.,Jogaite, V.,Manakova, E.,Grazulis, S.,Tumkevicius, S.,Matulis, D. Benzenesulfonamides with pyrimidine moiety as inhibitors of human carbonic anhydrases I, II, VI, VII, XII, and XIII Bioorg.Med.Chem., 21:6937-6947, 2013 Cited by PubMed Abstract: Two groups of benzenesulfonamide derivatives, bearing pyrimidine moieties, were designed and synthesized as inhibitors of carbonic anhydrases (CA). Their binding affinities to six recombinant human CA isoforms I, II, VI, VII, XII, and XIII were determined by the thermal shift assay (TSA). The binding of several inhibitors was measured by isothermal titration calorimetry (ITC). Direct demonstration of compound inhibition was achieved by determining the inhibition constant by stopped-flow CO2 hydration assay. The most potent compounds demonstrated selectivity towards isoform I and affinities of 0.5 nM. The crystal structures of selected compounds in complex with CA II, XII, and XIII were determined to atomic resolution. Compounds described here were compared with previously published pyrimidinebenzenesulfonamides.(1) Systematic structure-activity analysis of 40 compound interactions with six isoforms yields clues for the design of compounds with greater affinities and selectivities towards target CA isoforms. PubMed: 24103428DOI: 10.1016/j.bmc.2013.09.029 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.45 Å) |
Structure validation
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