3VBD

Complex of human carbonic anhydrase II with 4-(6-methoxy-3,4-dihydroisoquinolin-1-yl)benzenesulfonamide

3VBD の概要

• エントリーDOI: 10.2210/pdb3vbd/pdb
• 関連するPDBエントリー: 3V7X
• 分子名称: Carbonic anhydrase 2, ZINC ION, 4-(6-methoxy-3,4-dihydroisoquinolin-1-yl)benzenesulfonamide, ... (6 entities in total)
• 機能のキーワード: 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: 30367.24

構造登録者

Mader, P.,Brynda, J.,Rezacova, P. (登録日: 2012-01-02, 公開日: 2012-04-04, 最終更新日: 2024-02-28)

主引用文献

Gitto, R.,Damiano, F.M.,Mader, P.,De Luca, L.,Ferro, S.,Supuran, C.T.,Vullo, D.,Brynda, J.,Rezacova, P.,Chimirri, A.
Synthesis, Structure-Activity Relationship Studies, and X-ray Crystallographic Analysis of Arylsulfonamides as Potent Carbonic Anhydrase Inhibitors.
J.Med.Chem., 55:3891-3899, 2012

PubMed Abstract: A series of arylsulfonamides has been synthesized and investigated for the inhibition of some selected human carbonic anhydrase isoforms. The studied compounds showed significant inhibitory effects in the nanomolar range toward druggable isoforms (hCA VII, hCA IX, and hCA XIV) (K(i) values from 4.8 to 61.7 nM), whereas they generally exhibited significant selectivity over hCA I and hCA II, that are ubiquitous and considered off-target isoforms. On the basis of biochemical data, we herein discussed structure-affinity relationships for this series of arylsulfonamides, suggesting a key role for alkoxy substituents in CA inhibition. Furthermore, X-ray crystal structures of complexes of two active inhibitors (I and 2a) with hCA II allowed us to elucidate the main interactions between the inhibitor and specific amino acid residues within the catalytic site.

PubMed: 22443141
DOI: 10.1021/jm300112w

実験手法

X-RAY DIFFRACTION (1.05 Å)