6EQU

X-Ray crystal structure of the human carbonic anhydrase II adduct with a membrane-impermeant inhibitor

6EQU の概要

• エントリーDOI: 10.2210/pdb6equ/pdb
• 分子名称: Carbonic anhydrase 2, ZINC ION, 4-[2-(2,4,6-triphenylpyridin-1-ium-1-yl)ethyl]benzenesulfonamide, ... (4 entities in total)
• 機能のキーワード: human carbonic anhydrase ii, membrane-impermeant inhibitor, complex, lyase
• 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: 29903.14

構造登録者

Alterio, V.,De Simone, G.,Esposito, D. (登録日: 2017-10-15, 公開日: 2017-12-13, 最終更新日: 2024-01-17)

主引用文献

Alterio, V.,Esposito, D.,Monti, S.M.,Supuran, C.T.,De Simone, G.
Crystal structure of the human carbonic anhydrase II adduct with 1-(4-sulfamoylphenyl-ethyl)-2,4,6-triphenylpyridinium perchlorate, a membrane-impermeant, isoform selective inhibitor.
J Enzyme Inhib Med Chem, 33:151-157, 2018

PubMed Abstract: Pyridinium containing sulfonamides have been largely investigated as carbonic anhydrase inhibitors (CAIs), showing interesting selectivity features. Nevertheless, only few structural studies are so far available on adducts that these compounds form with diverse CA isoforms. In this paper, we report the structural characterization of the adduct that a triphenylpyridinium derivative forms with hCA II, showing that the substitution of the pyridinium ring plays a key role in determining the conformation of the inhibitor in the active site and consequently the binding affinity to the enzyme. These findings open new perspectives on the basic structural requirements for designing sulfonamide CAIs with a selective inhibition profile.

PubMed: 29199489
DOI: 10.1080/14756366.2017.1405263

実験手法

X-RAY DIFFRACTION (1.65 Å)