4RFC

Human carbonic anhydrase II in complex with tert-butyl 4-(4-sulfamoylphenoxy)butylcarbamate

4RFC の概要

• エントリーDOI: 10.2210/pdb4rfc/pdb
• 関連するPDBエントリー: 4RFD
• 分子名称: Carbonic anhydrase 2, ZINC ION, tert-butyl 4-(4-sulfamoylphenoxy)butylcarbamate, ... (4 entities in total)
• 機能のキーワード: sulfonamide, carbonic anhydrase, antiglaucoma, o-(-aminoalkyl)-benzenesulfonamides, 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: 29698.90

構造登録者

Bozdag, M.,Pinard, M.A.,Carta, F.,Masini, E.,Scozzafava, A.,Mckenna, R.,Supuran, C.T. (登録日: 2014-09-25, 公開日: 2015-04-15, 最終更新日: 2024-02-28)

主引用文献

Bozdag, M.,Pinard, M.,Carta, F.,Masini, E.,Scozzafava, A.,McKenna, R.,Supuran, C.T.
A class of 4-sulfamoylphenyl-omega-aminoalkyl ethers with effective carbonic anhydrase inhibitory action and antiglaucoma effects.
J.Med.Chem., 57:9673-9686, 2014

PubMed Abstract: We report a series of 4-sulfamoylphenyl-ω-aminoalkyl ethers as carbonic anhydrase (CA, EC 4.2.1.1) inhibitors. The structure-activity relationship was drawn for the inhibition of four physiologically relevant isoforms: hCA I, II, IX, and XII. Many of these compounds were highly effective, low nanomolar inhibitors of all CA isoforms, whereas several isoform-selective were also identified. X-ray crystal structures of two new sulfonamides bound to the physiologically dominant CA II isoform showed the tails of these derivatives bound within the hydrophobic half of the enzyme active site through van der Waals contacts with Val135, Leu198, Leu204, Trp209, Pro201, and Pro202 amino acids. One of the highly water-soluble compound (as trifluoroacetate salt) showed effective IOP lowering properties in an animal model of glaucoma. Several fluorescent sulfonamides incorporating either the fluorescein-thiourea (7a-c) or tetramethylrhodamine-thiourea (9a,b) moieties were also obtained and showed interesting CA inhibitory properties for the tumor-associated isoforms CA IX and XII.

PubMed: 25358036
DOI: 10.1021/jm501497m

実験手法

X-RAY DIFFRACTION (1.645 Å)