3M67

Crystal structure of human carbonic anhydrase isozyme II with 2-chloro-5-[(6,7-dihydro-1H-[1,4]dioxino[2,3-f]benzimidazol-2-ylsulfanyl)acetyl]benzenesulfonamide

3M67 の概要

• エントリーDOI: 10.2210/pdb3m67/pdb
• 関連するPDBエントリー: 3m2n 3m3x 3m40 3m5e
• 分子名称: Carbonic anhydrase 2, 2-chloro-5-[(6,7-dihydro-1H-[1,4]dioxino[2,3-f]benzimidazol-2-ylsulfanyl)acetyl]benzenesulfonamide, ZINC ION, ... (5 entities in total)
• 機能のキーワード: drug design, carbonic anhydrase, benzenesulfonamide, metal-binding, lyase-lyase inhibitor complex, lyase/lyase inhibitor
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Cytoplasm: P00918
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 29950.63

構造登録者

Grazulis, S.,Manakova, E.,Golovenko, D. (登録日: 2010-03-15, 公開日: 2010-11-03, 最終更新日: 2023-11-01)

主引用文献

Capkauskaite, E.,Baranauskiene, L.,Golovenko, D.,Manakova, E.,Grazulis, S.,Tumkevicius, S.,Matulis, D.
Indapamide-like benzenesulfonamides as inhibitors of carbonic anhydrases I, II, VII, and XIII
Bioorg.Med.Chem., 18:7357-7364, 2010

PubMed Abstract: A series of novel 2-chloro-5-[(1-benzimidazolyl- and 2-benzimidazolylsulfanyl)acetyl]benzene-sulfonamides were designed and synthesized. Their binding to recombinant human carbonic anhydrase (hCA) isozymes I, II, VII, and XIII was determined by isothermal titration calorimetry and thermal shift assay. The designed S-alkylated benzimidazole derivatives exhibited stronger binding than the indapamide-like N-alkylated benzimidazoles, with the K(d) reaching about 50-100 nM with drug-targeted hCAs VII and XIII. The cocrystal structures of selected compounds with hCA II were determined by X-ray crystallography, and structural features of the binding event were revealed.

PubMed: 20926301
DOI: 10.1016/j.bmc.2010.09.016

実験手法

X-RAY DIFFRACTION (1.8 Å)