3V5G

Crystal structure of human carbonic anhydrase II in complex with the 4-sulfamido-benzenesulfonamide inhibitor

3V5G の概要

• エントリーDOI: 10.2210/pdb3v5g/pdb
• 関連するPDBエントリー: 1CA2
• 分子名称: Carbonic anhydrase 2, ZINC ION, MERCURIBENZOIC ACID, ... (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: 30768.73

構造登録者

D'Ambrosio, K.,De Simone, G. (登録日: 2011-12-16, 公開日: 2012-07-25, 最終更新日: 2023-09-13)

主引用文献

D'Ambrosio, K.,Smaine, F.Z.,Carta, F.,De Simone, G.,Winum, J.Y.,Supuran, C.T.
Development of potent carbonic anhydrase inhibitors incorporating both sulfonamide and sulfamide groups.
J.Med.Chem., 55:6776-6783, 2012

PubMed Abstract: A series of compounds incorporating both sulfonamide and sulfamide as zinc-binding groups (ZBGs) are reported as inhibitors of the metalloenzyme carbonic anhydrase (CA, EC 4.2.1.1). Crystallographic studies on the complex of hCA II with the lead compound of this series, namely, 4-sulfamido-benzenesulfonamide, revealed the binding of two molecules in the enzyme active site cavity, the first one canonically coordinated to the zinc ion by means of the sulfonamide group and the second one located at the entrance of the cavity. This observation led to the design of elongated molecules incorporating these two ZBGs, separated by a linker of proper length, to allow the simultaneous binding to these different sites. The "long" inhibitors indeed showed around 10 times better enzyme inhibitory properties as compared to the shorter molecules against four physiologically relevant human (h) isoforms, hCA I, II, IX, and XII.

PubMed: 22775345
DOI: 10.1021/jm300818k

実験手法

X-RAY DIFFRACTION (1.5 Å)