3BL0

Carbonic anhydrase inhibitors. Interaction of 2-N,N-Dimethylamino-1,3,4-thiadiazole-5-methanesulfonamide with twelve mammalian isoforms: kinetic and X-Ray crystallographic studies

3BL0 の概要

• エントリーDOI: 10.2210/pdb3bl0/pdb
• 関連するPDBエントリー: 2EU2 2EU3 3BL1
• 分子名称: Carbonic anhydrase 2, ZINC ION, 1-[5-(dimethylamino)-1,3,4-thiadiazol-2-yl]methanesulfonamide, ... (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: 29898.46

構造登録者

Temperini, C.,Supuran, C.T.,Blackburn, G.M. (登録日: 2007-12-10, 公開日: 2008-01-22, 最終更新日: 2024-02-21)

主引用文献

Temperini, C.,Cecchi, A.,Boyle, N.A.,Scozzafava, A.,Cabeza, J.E.,Wentworth, P.,Blackburn, G.M.,Supuran, C.T.
Carbonic anhydrase inhibitors. Interaction of 2-N,N-dimethylamino-1,3,4-thiadiazole-5-methanesulfonamide with 12 mammalian isoforms: kinetic and X-ray crystallographic studies.
Bioorg.Med.Chem.Lett., 18:999-1005, 2008

PubMed Abstract: 2-N,N-Dimethylamino-1,3,4-thiadiazole-5-methanesulfonamide was tested for its interaction with the 12 catalytically active mammalian carbonic anhydrase (CA, EC 4.2.1.1) isozymes, CA I-XIV. The compound is a potent inhibitor of CA IV, VII, IX, XII, and XIII (K(I)s of 0.61-39 nM), a medium potency inhibitor of CA II and VA (K(I)s of 121-438 nM), and a weak inhibitor against the other isoforms (CA III, VB, VI, and XIV), making it a very interesting candidate for situations in which a strong/selective inhibition of certain isozymes is needed. The crystal structure of the hCA II adduct of this sulfonamide revealed interesting interactions between the inhibitor and the enzyme which are quite different from those observed in the adducts of CA II with the structurally related aliphatic derivatives zonisamide, 2-amino-1,3,4-thiadiazolyl-5-difluoromethanesulfonamide, and 2-dimethylamino-5-[sulfonamido-(aminomethyl)]-1,3,4-thiadiazole reported earlier.

PubMed: 18162396
DOI: 10.1016/j.bmcl.2007.12.022

実験手法

X-RAY DIFFRACTION (1.9 Å)