5NEE

Crystal structure of human carbonic anhydrase II in complex with the inhibitor 5-[2-(morpholine-4-carbonyl)1,3-oxazol-5-yl)]thiophene-2-sulfonammide

5NEE の概要

• エントリーDOI: 10.2210/pdb5nee/pdb
• 分子名称: Carbonic anhydrase 2, ZINC ION, 5-(2-morpholin-4-ylcarbonyl-1,3-oxazol-5-yl)thiophene-2-sulfonamide, ... (5 entities in total)
• 機能のキーワード: 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: 29789.94

構造登録者

Ferraroni, M.,Supuran, C.T.,Krasavin, M. (登録日: 2017-03-10, 公開日: 2017-12-06, 最終更新日: 2024-01-17)

主引用文献

Ferraroni, M.,Lucarini, L.,Masini, E.,Korsakov, M.,Scozzafava, A.,Supuran, C.T.,Krasavin, M.
1,3-Oxazole-based selective picomolar inhibitors of cytosolic human carbonic anhydrase II alleviate ocular hypertension in rabbits: Potency is supported by X-ray crystallography of two leads.
Bioorg. Med. Chem., 25:4560-4565, 2017

PubMed Abstract: Two lead 1,3-oxazole-based carbonic anhydrase inhibitors (CAIs) earlier identified as selective, picomolar inhibitors of hCA II (a cytosolic target for treatment of glaucoma) have been investigated further. Firstly, they were found to be conveniently synthesized on multigram scale, which enables further development. These compounds were found to be comparable in efficacy to dorzolamide eye drops when applied in the eye drop form as well. Finally, the reasons for unusually high potency of these compounds became understood from their high-resolution X-ray crystallography structures. These data significantly expand our understanding of heterocycle-based primary sulfonamides, many of which have recently emerged from our labs - particularly, from the corneal permeability standpoint.

PubMed: 28728897
DOI: 10.1016/j.bmc.2017.06.054

実験手法

X-RAY DIFFRACTION (1.7 Å)