4HU1

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

4HU1 の概要

• エントリーDOI: 10.2210/pdb4hu1/pdb
• 関連するPDBエントリー: 4HT0 4HT2
• 分子名称: Carbonic anhydrase 13, ZINC ION, 2,3,5,6-tetrafluoro-4-[(2-hydroxyethyl)sulfonyl]benzenesulfonamide, ... (6 entities in total)
• 機能のキーワード: drug design, carbonic anhydrase, benzenesulfonamide, metal-binding, lyase-lyase inhibitor complex, carbonate dehydratase activity, carbon-oxygen lyase activity, lyase/lyase inhibitor
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 60572.59

構造登録者

Smirnov, A.,Manakova, E.,Grazulis, S. (登録日: 2012-11-02, 公開日: 2013-04-10, 最終更新日: 2023-09-20)

主引用文献

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

実験手法

X-RAY DIFFRACTION (1.95 Å)