1EOU

CRYSTAL STRUCTURE OF HUMAN CARBONIC ANHYDRASE II COMPLEXED WITH AN ANTICONVULSANT SUGAR SULFAMATE

1EOU の概要

• エントリーDOI: 10.2210/pdb1eou/pdb
• 関連するPDBエントリー: 1AM6
• 分子名称: CARBONIC ANHYDRASE II (CA II), ZINC ION, SULFAMIC ACID 2,3-O-(1-METHYLETHYLIDENE)-4,5-O-SULFONYL-BETA-FRUCTOPYRANOSE ESTER, ... (4 entities in total)
• 機能のキーワード: hydrolase, co2 hydration, protein-inhibitor complex, 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: 29715.82

構造登録者

Recacha, R.,Costanzo, M.J.,Maryanoff, B.E.,Chattopadhyay, D. (登録日: 2000-03-24, 公開日: 2002-02-13, 最終更新日: 2024-03-13)

主引用文献

Recacha, R.,Costanzo, M.J.,Maryanoff, B.E.,Chattopadhyay, D.
Crystal structure of human carbonic anhydrase II complexed with an anti-convulsant sugar sulphamate.
Biochem.J., 361:437-441, 2002

PubMed Abstract: The fructose-based sugar sulphamate RWJ-37497, a potent analogue of the widely used anti-epileptic drug topiramate, possesses anti-convulsant and carbonic anhydrase-inhibitory activities. We have studied the binding interactions of RWJ-37497 in the active site of human carbonic anhydrase II by X-ray crystallography. The atomic positions of the enzyme inhibitor complex were refined at a resolution of 2.1 A (1 A=0.1 nm) to the final crystallographic R and R(free) values of 0.18 and 0.23, respectively. The inhibitor co-ordinates to the active-site zinc ion through its oxygen atom and the ionized nitrogen atom of the sulphamate group by replacing the metal-bound water molecules, although the sulphamoyl oxygen atom provides a rather lengthy co-ordination. The 4,5-cyclic sulphate group is positioned in a hydrophobic pocket of the active site, making contacts with the residues Phe-131, Leu-198, Pro-201 and Pro-202. Since the ligand was found to be intact, concerns about RWJ-37947 irreversibly alkylating the enzyme through its 4,5-cyclic sulphate group were dispelled.

PubMed: 11802772
DOI: 10.1042/0264-6021:3610437

実験手法

X-RAY DIFFRACTION (2.1 Å)