3B4F

Carbonic anhydrase inhibitors. Interaction of 2-(hydrazinocarbonyl)-3-phenyl-1H-indole-5-sulfonamide with twelve mammalian isoforms: kinetic and X-Ray crystallographic studies

3B4F の概要

• エントリーDOI: 10.2210/pdb3b4f/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, sulfonamide, acetylation, cytoplasm, disease mutation, lyase, metal-binding, polymorphism, zinc, lyase(oxo-acid)
• 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: 29885.42

構造登録者

Guzel, o.,Temperini, c.,Innocenti, a.,Scozzafava, A.,Salman, a.,Supuran, c.t. (登録日: 2007-10-24, 公開日: 2008-01-22, 最終更新日: 2023-08-30)

主引用文献

Guzel, O.,Temperini, C.,Innocenti, A.,Scozzafava, A.,Salman, A.,Supuran, C.T.
Carbonic anhydrase inhibitors. Interaction of 2-(hydrazinocarbonyl)-3-phenyl-1H-indole-5-sulfonamide with 12 mammalian isoforms: kinetic and X-ray crystallographic studies.
Bioorg.Med.Chem.Lett., 18:152-158, 2008

PubMed Abstract: 2-(Hydrazinocarbonyl)-3-phenyl-1H-indole-5-sulfonamide was tested for its interaction with 12 carbonic anhydrase (CA, EC 4.2.1.1) isoforms in the search of compounds with good inhibitory activity against isozymes with medicinal chemistry applications, such as CA I, II, VA, VB, VII, IX, and XII among others. This sulfonamide is a potent inhibitor of CA I and II (K(I)s of 7.2-7.5 nM), a medium potency inhibitor of CA VII, IX, XII, and XIV, and a weak inhibitor against the other ubiquitous isoforms, making it thus a very interesting clinical candidate for situations in which a strong inhibition of CA I and II is needed. The crystal structure of the hCA II adduct of this sulfonamide revealed many favorable interactions between the inhibitor and the enzyme which explain its strong low nanomolar affinity for this isoform but may also be exploited for the design of effective inhibitors incorporating bicyclic moieties.

PubMed: 18024029
DOI: 10.1016/j.bmcl.2007.10.110

実験手法

X-RAY DIFFRACTION (1.89 Å)