3HKT

Human carbonic anhydrase II in complex with alpha-D-Glucopyranosyl-(1->4)-1-thio-beta-D-glucopyranosylsulfonamide

3HKT の概要

• エントリーDOI: 10.2210/pdb3hkt/pdb
• 関連するPDBエントリー: 3HKQ 3HKU
• 分子名称: Carbonic anhydrase 2, alpha-D-galactopyranose-(1-4)-(1S)-1,5-anhydro-1-sulfamoyl-D-galactitol, ZINC ION, ... (4 entities in total)
• 機能のキーワード: carbonic anhydrase drug design, acetylation, cytoplasm, disease mutation, lyase, metal-binding, polymorphism, zinc
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 29759.85

構造登録者

Paul, B.,Poulsen, S.-A.,Hofmann, A. (登録日: 2009-05-25, 公開日: 2009-10-13, 最終更新日: 2024-03-20)

主引用文献

Lopez, M.,Paul, B.,Hofmann, A.,Morizzi, J.,Wu, Q.K.,Charman, S.A.,Innocenti, A.,Vullo, D.,Supuran, C.T.,Poulsen, S.A.
S-glycosyl primary sulfonamides--a new structural class for selective inhibition of cancer-associated carbonic anhydrases.
J.Med.Chem., 52:6421-6432, 2009

PubMed Abstract: In this paper, we present a new class of carbonic anhydrase (CA) inhibitor that was designed to selectively target the extracellular domains of the cancer-relevant CA isozymes. The aromatic moiety of the classical zinc binding sulfonamide CA inhibitors is absent from these compounds and instead they incorporate a hydrophilic mono- or disaccharide fragment directly attached to the sulfonamide group to give S-glycosyl primary sulfonamides (1-10). The inhibition properties of these compounds at the physiologically abundant human CA isozymes I and II and cancer-associated IX and XII were determined, and all compounds had moderate potency with K(i)s in the micromolar range. We present the crystal structures of anomeric sulfonamides 4, 7, and 10 and the sugar sulfamate drug topiramate in complex with human recombinant CA II. From these structures, we have obtained valuable insights into ligand-protein interactions of these novel carbohydrate-based sulfonamides with CA.

PubMed: 19827837
DOI: 10.1021/jm900914e

実験手法

X-RAY DIFFRACTION (2.36 Å)