2O4Z

Crystal structure of the Carbonic Anhydrase II complexed with hydroxysulfamide inhibitor

2O4Z の概要

• エントリーDOI: 10.2210/pdb2o4z/pdb
• 分子名称: Carbonic anhydrase 2, ZINC ION, MERCURY (II) ION, ... (5 entities in total)
• 機能のキーワード: carbonic anhydrase, inhibitors, 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: 29667.17

構造登録者

Temperini, C.,Winum, J.Y.,Montero, J.L.,Scozzafava, a.,Supuran, c.t. (登録日: 2006-12-05, 公開日: 2007-05-15, 最終更新日: 2023-08-30)

主引用文献

Temperini, C.,Winum, J.Y.,Montero, J.L.,Scozzafava, A.,Supuran, C.T.
Carbonic anhydrase inhibitors: The X-ray crystal structure of the adduct of N-hydroxysulfamide with isozyme II explains why this new zinc binding function is effective in the design of potent inhibitors.
Bioorg.Med.Chem.Lett., 17:2795-2801, 2007

PubMed Abstract: N-Hydroxysulfamide is a 2000-fold more potent inhibitor of the zinc enzyme carbonic anhydrase (CA, EC 4.2.1.1) as compared to sulfamide. It also inhibits other physiologically relevant isoforms, such as the tumor-associated CA IX and XII (K(I)s in the range of 0.865-1.34microM). In order to understand the binding of this inhibitor to the enzyme active site, the X-ray crystal structure of the human hCA II-N-hydroxysulfamide adduct was resolved. The inhibitor coordinates to the active site zinc ion by the ionized primary amino group, participating in an extended network of hydrogen bonds with amino acid residues Thr199, Thr200 and two water molecules. The additional two hydrogen bonds in which N-hydroxysulfamide bound to hCA II is involved as compared to the corresponding adduct of sulfamide may explain its higher affinity for the enzyme, also providing hints for the design of tight-binding CA inhibitors possessing an organic moiety substituting the NH group in the N-hydroxysulfamide structure.

PubMed: 17346964
DOI: 10.1016/j.bmcl.2007.02.068

実験手法

X-RAY DIFFRACTION (2.1 Å)