5LJT

Crystal structure of human carbonic anhydrase II in complex with the 4-((1-phenyl-1H-1,2,3-triazol-4-yl)methoxy)benzenesulfonamide inhibitor

5LJT の概要

• エントリーDOI: 10.2210/pdb5ljt/pdb
• 分子名称: Carbonic anhydrase 2, ZINC ION, 4-[[4-[azanyl-bis(oxidanyl)-$l^{4}-sulfanyl]phenoxy]methyl]-1-phenyl-1,2,3-triazole, ... (5 entities in total)
• 機能のキーワード: 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: 29560.67

構造登録者

Ferraroni, M.,Supuran, C. (登録日: 2016-07-19, 公開日: 2017-06-21, 最終更新日: 2024-01-10)

主引用文献

Nocentini, A.,Ferraroni, M.,Carta, F.,Ceruso, M.,Gratteri, P.,Lanzi, C.,Masini, E.,Supuran, C.T.
Benzenesulfonamides Incorporating Flexible Triazole Moieties Are Highly Effective Carbonic Anhydrase Inhibitors: Synthesis and Kinetic, Crystallographic, Computational, and Intraocular Pressure Lowering Investigations.
J. Med. Chem., 59:10692-10704, 2016

PubMed Abstract: Herein we report the synthesis of two series of benzenesulfonamide containing compounds that incorporate the phenyl-1,2,3-triazole moieties. We explored the insertion of appropriate linkers, such as ether, thioether, and amino type, into the inner section of the molecules with the intent to confer additional flexibility. All obtained compounds were screened in vitro as inhibitors of the physiologically relevant human (h) isoforms of the metalloenzyme carbonic anhydrase (CA, EC 4.2.1.1). Many of them were low nanomolar or subnanomolar hCA II, IX, and XII inhibitors, whereas they did not potently inhibit hCA I. Computational and X-ray crystallographic studies of the enzyme-inhibitor adducts helped us to rationalize the obtained results. Some of the sulfonamides reported here showed significant intraocular pressure lowering activity in an animal model of glaucoma.

PubMed: 27933963
DOI: 10.1021/acs.jmedchem.6b01389

実験手法

X-RAY DIFFRACTION (1 Å)