3P5A

Human Carbonic Anhydrase complexed with Sodium morpholinocarbodithioate

3P5A の概要

• エントリーDOI: 10.2210/pdb3p5a/pdb
• 関連するPDBエントリー: 3P58 3P5L
• 分子名称: Carbonic anhydrase 2, ZINC ION, morpholine-4-carbodithioic acid, ... (5 entities in total)
• 機能のキーワード: carbothioates, hcaii inhibitors, lyase-inhibitor complex, lyase/inhibitor
• 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: 29595.87

構造登録者

Aggarwal, M.,McKenna, R. (登録日: 2010-10-08, 公開日: 2011-10-19, 最終更新日: 2024-02-21)

主引用文献

Carta, F.,Aggarwal, M.,Maresca, A.,Scozzafava, A.,McKenna, R.,Masini, E.,Supuran, C.T.
Dithiocarbamates strongly inhibit carbonic anhydrases and show antiglaucoma action in vivo
J.Med.Chem., 55:1721-1730, 2012

PubMed Abstract: A series of dithiocarbamates were prepared by reaction of primary/secondary amines with carbon disulfide in the presence of bases. These compounds were tested for the inhibition of four human (h) isoforms of the zinc enzyme carbonic anhydrase, CA (EC 4.2.1.1), hCA I, II, IX, and XII, involved in pathologies such as glaucoma (CA II and XII) or cancer (CA IX). Several low nanomolar inhibitors targeting these CAs were detected. The X-ray crystal structure of the hCA II adduct with morpholine dithiocarbamate evidenced the inhibition mechanism of these compounds, which coordinate to the metal ion through a sulfur atom from the dithiocarbamate zinc-binding function. Some dithiocarbamates showed an effective intraocular pressure lowering activity in an animal model of glucoma.

PubMed: 22276570
DOI: 10.1021/jm300031j

実験手法

X-RAY DIFFRACTION (1.49 Å)