1I90

CARBONIC ANHYDRASE II COMPLEXED WITH AL-8520 2H-THIENO[3,2-E]-1,2-THIAZINE-6-SULFONAMIDE, 4-AMINO-3,4-DIHYDRO-2-(3-METHOXYPROPYL)-, 1,1-DIOXIDE, (R)

1I90 の概要

• エントリーDOI: 10.2210/pdb1i90/pdb
• 関連するPDBエントリー: 1I8z 1I91
• 分子名称: CARBONIC ANHYDRASE II, ZINC ION, MERCURY (II) ION, ... (5 entities in total)
• 機能のキーワード: carbonic anhydrase ii, al-8520, 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: 29777.30

構造登録者

Kim, C.-Y.,Chang, J.S.,Liao, J.,May, J.A.,Christianson, D.W. (登録日: 2001-03-16, 公開日: 2001-03-28, 最終更新日: 2024-02-07)

主引用文献

Kim, C.Y.,Whittington, D.A.,Chang, J.S.,Liao, J.,May, J.A.,Christianson, D.W.
Structural aspects of isozyme selectivity in the binding of inhibitors to carbonic anhydrases II and IV.
J.Med.Chem., 45:888-893, 2002

PubMed Abstract: Carbonic anhydrase inhibitors are effective in lowering intraocular pressure, the primary indication of glaucoma. Human carbonic anhydrase II, and possibly carbonic anhydrase IV (CAII and CAIV, respectively), help regulate fluid secretion into the anterior chamber of the eye. Because inhibitors currently formulated as drugs to treat glaucoma were designed to target CAII, an understanding of the structural basis of CAII-CAIV discrimination by inhibitors would be useful for probing the role of each isozyme in the etiology of the disease. Here, we report the X-ray crystal structures of three novel thieno[3,2-e]-1,2-thiazine-6-sulfonamides complexed with CAII and the computationally predicted structures of the same compounds complexed with CAIV. All three compounds bind with similar affinity to CAII, but they bind with up to 100-fold lower affinities to CAIV. Comparisons of experimentally determined structures of CAII-inhibitor complexes and computationally predicted structures of CAIV-inhibitor complexes allow us to rationalize these affinity trends and outline molecular features that may contribute to high-affinity inhibitor binding to CAIV. This study demonstrates how experimental structure determination methods and computational structure prediction methods can be used together to answer questions that cannot be answered by either method alone.

PubMed: 11831900
DOI: 10.1021/jm010163d

実験手法

X-RAY DIFFRACTION (2 Å)