4XE1

Human carbonic anhydrase II in complex with 6-SULFAMOYL-SACCHARIN

4XE1 の概要

• エントリーDOI: 10.2210/pdb4xe1/pdb
• 分子名称: Carbonic anhydrase 2, ZINC ION, GLYCEROL, ... (6 entities in total)
• 機能のキーワード: cytoplasm, 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: 30327.88

構造登録者

Alterio, V.,De Simone, G. (登録日: 2014-12-21, 公開日: 2015-03-18, 最終更新日: 2024-01-10)

主引用文献

Alterio, V.,Tanc, M.,Ivanova, J.,Zalubovskis, R.,Vozny, I.,Monti, S.M.,Di Fiore, A.,De Simone, G.,Supuran, C.T.
X-ray crystallographic and kinetic investigations of 6-sulfamoyl-saccharin as a carbonic anhydrase inhibitor.
Org.Biomol.Chem., 13:4064-4069, 2015

PubMed Abstract: 6-Sulfamoyl-saccharin was investigated as an inhibitor of 11 α-carbonic anhydrase (CA, EC 4.2.1.1) isoforms of human (h) origin, hCA I-XIV, and X-ray crystallographic data were obtained for its adduct with hCA II, the physiologically dominant isoform. This compound possesses two potential zinc-binding groups, the primary sulfamoyl one and the secondary, acylatedsulfonamide. Saccharin itself binds to the Zn(II) ion from the CA active site coordinating with this last group, in deprotonated (SO2N(-)CO) form. Here we explain why 6-sulfamoyl-saccharin, unlike saccharin, binds to the metal ion from the hCA II active site by its primary sulfonamide moiety and not the secondary one as saccharin itself. Our study is useful for shedding new light to the structure-based drug design of isoform-selective CA inhibitors of the sulfonamide type.

PubMed: 25733161
DOI: 10.1039/c4ob02648a

実験手法

X-RAY DIFFRACTION (1.8 Å)