6XXT

The crystal structure of hCA II in complex with a 4-(4-aroylpiperazine-1-carbonyl)benzenesulfonamide derivative.

6XXT の概要

• エントリーDOI: 10.2210/pdb6xxt/pdb
• 分子名称: Carbonic anhydrase 2, ZINC ION, 4-[4-(phenylcarbonyl)piperazin-1-yl]carbonylbenzenesulfonamide, ... (5 entities in total)
• 機能のキーワード: protein-inhibitor adduct, lyase
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 30008.24

構造登録者

Di Fiore, A.,De Simone, G. (登録日: 2020-01-28, 公開日: 2020-06-03, 最終更新日: 2024-01-24)

主引用文献

Mancuso, F.,Di Fiore, A.,De Luca, L.,Angeli, A.,Monti, S.M.,De Simone, G.,Supuran, C.T.,Gitto, R.
Looking toward the Rim of the Active Site Cavity of Druggable Human Carbonic Anhydrase Isoforms.
Acs Med.Chem.Lett., 11:1000-1005, 2020

PubMed Abstract: We report the synthesis and biochemical evaluation of a series of substituted 4-(4-aroylpiperazine-1-carbonyl)benzenesulfonamides (-) developed as inhibitors of druggable carbonic anhydrase (CA) isoforms, as tools for the identification of new therapeutics. X-ray crystallography confirmed that this class of benzenesulfonamides binds CAs through the canonical anchoring of the benzenesulfonamide moiety to the metal ion and a recognition of the middle/top area of the active site cavity. Compound (R = 2-Cl) demonstrated relevant selectivity toward brain-expressed hCA VII. The best balancing in binding affinity and selectivity toward tumor-expressed hCA IX/hCA XII over ubiquitous hCA I/hCA II was found for inhibitor (R = 3-NO). Notably (R = 2-F) proved to be the most efficacious inhibitor of hCA XII for which computational studies elucidated the CA recognition process.

PubMed: 32435417
DOI: 10.1021/acsmedchemlett.0c00062

実験手法

X-RAY DIFFRACTION (1.05 Å)