4HT2

Crystal structure of human carbonic anhydrase isozyme XII with the inhibitor.

Summary for 4HT2

• Entry DOI: 10.2210/pdb4ht2/pdb
• Descriptor: Carbonic anhydrase 12, ZINC ION, 4-[(4,6-dimethylpyrimidin-2-yl)thio]-2,3,5,6-tetrafluorobenzenesulfonamide, ... (6 entities in total)
• Functional Keywords: drug design, carbonic anhydrase, benzenesulfonamide, metal-binding, lyase-lyase inhibitor complex, catalytic activity, carbon-oxygen lyase activity, carbonate dehydratase activity, membrane, 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: 122463.45

Authors

Smirnov, A.,Manakova, E.,Grazulis, S. (deposition date: 2012-10-31, release date: 2013-04-10, Last modification date: 2023-09-20)

Primary citation

Dudutiene, V.,Zubriene, A.,Smirnov, A.,Gylyte, J.,Timm, D.,Manakova, E.,Grazulis, S.,Matulis, D.
4-Substituted-2,3,5,6-tetrafluorobenzenesulfonamides as inhibitors of carbonic anhydrases I, II, VII, XII, and XIII.
Bioorg.Med.Chem., 21:2093-2106, 2013

PubMed Abstract: A series of 4-substituted-2,3,5,6-tetrafluorobenezenesulfonamides were synthesized and their binding potencies as inhibitors of recombinant human carbonic anhydrase isozymes I, II, VII, XII, and XIII were determined by the thermal shift assay, isothermal titration calorimetry, and stop-flow CO2 hydration assay. All fluorinated benzenesulfonamides exhibited nanomolar binding potency toward tested CAs and fluorinated benzenesulfonamides posessed higher binding potency than non-fluorinated compounds. The crystal structures of 4-[(4,6-dimethylpyrimidin-2-yl)thio]-2,3,5,6-tetrafluorobenzenesulfonamide in complex with CA II and CA XII, and 2,3,5,6-tetrafluoro-4-[(2-hydroxyethyl)sulfonyl]benzenesulfonamide in complex with CA XIII were determined. The observed dissociation constants for several fluorinated compounds reached subnanomolar range for CA I isozyme. The affinity and the selectivity of the compounds towards tested isozymes are presented.

PubMed: 23394791
DOI: 10.1016/j.bmc.2013.01.008

Experimental method

X-RAY DIFFRACTION (1.45 Å)