4RUZ

Crystal structure of human Carbonic Anhydrase II in complex with 4-ethoxybenzenesulfonamide

4RUZ の概要

• エントリーDOI: 10.2210/pdb4ruz/pdb
• 関連するPDBエントリー: 4RUX 4RUY
• 分子名称: Carbonic anhydrase 2, ZINC ION, 4-ethoxybenzenesulfonamide, ... (5 entities in total)
• 機能のキーワード: metalloenzyme, analgesic, 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: 29849.05

構造登録者

Pinard, M.A.,Mckenna, R. (登録日: 2014-11-23, 公開日: 2015-04-22, 最終更新日: 2024-02-28)

主引用文献

Carta, F.,Di Cesare Mannelli, L.,Pinard, M.,Ghelardini, C.,Scozzafava, A.,McKenna, R.,Supuran, C.T.
A class of sulfonamide carbonic anhydrase inhibitors with neuropathic pain modulating effects.
Bioorg.Med.Chem., 23:1828-1840, 2015

PubMed Abstract: A series of benzene sulfonamide carbonic anhydrase (CA, EC 4.2.1.1) inhibitors which incorporate lipophilic 4-alkoxy- and 4-aryloxy moieties, together with several derivatives of ethoxzolamide and sulfanilamide are reported. These derivatives were investigated as inhibitors of the metalloenzyme carbonic anhydrase (CA, EC 4.2.1.1) of which multiple isoforms are known, and some appear to be involved in pain. These sulfonamides showed modest inhibition against the cytosolic isoform CA I, but were generally effective, low nanomolar CA II, VII, IX and XII inhibitors. X-ray crystallographic data for the adduct of several such sulfonamides with CA II allowed us to rationalize the good inhibition data. In a mice model of neuropathic pain induced by oxaliplatin, one of the strong CA II/VII inhibitors reported here induced a long lasting pain relieving effect, a fact never observed earlier. This is the first report of rationally designed sulfonamide CA inhibitors with pain effective modulating effects.

PubMed: 25766630
DOI: 10.1016/j.bmc.2015.02.027

実験手法

X-RAY DIFFRACTION (1.63 Å)