7QGZ

Human carbonic anhydrase II in complex with Methyl 3-((4-methylthiazol-2-yl)(4-sulfamoylphenyl)amino)propanoate

7QGZ の概要

• エントリーDOI: 10.2210/pdb7qgz/pdb
• 分子名称: Carbonic anhydrase 2, ZINC ION, methyl 3-[(4-methyl-1,3-thiazol-2-yl)-(4-sulfamoylphenyl)amino]propanoate, ... (4 entities in total)
• 機能のキーワード: drug design, carbonic anhydrase, benzenesulfonamide, metal-binding, lyase-lyase inhibitor complex, lyase
• 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: 29709.90

構造登録者

Paketuryte-Latve, V.,Smirnov, A.,Manakova, E.,Grazulis, S. (登録日: 2021-12-10, 公開日: 2022-05-04, 最終更新日: 2024-01-31)

主引用文献

Balandis, B.,Simkunas, T.,Paketuryte-Latve, V.,Michailoviene, V.,Mickeviciute, A.,Manakova, E.,Grazulis, S.,Belyakov, S.,Kairys, V.,Mickevicius, V.,Zubriene, A.,Matulis, D.
Beta and Gamma Amino Acid-Substituted Benzenesulfonamides as Inhibitors of Human Carbonic Anhydrases.
Pharmaceuticals, 15:-, 2022

PubMed Abstract: A series of novel benzenesulfonamide derivatives were synthesized bearing - β,γ-amino acid or - β-amino acid and thiazole moieties and their binding to the human carbonic anhydrase (CA) isozymes determined. These enzymes are involved in various illnesses, such as glaucoma, altitude sickness, epilepsy, obesity, and even cancer. There are numerous compounds that are inhibitors of CA and used as pharmaceuticals. However, most of them bind to most CA isozymes with little selectivity. The design of high affinity and selectivity towards one CA isozyme remains a significant challenge. The beta and gamma amino acid-substituted compound affinities were determined by the fluorescent thermal shift assay and isothermal titration calorimetry for all 12 catalytically active human carbonic anhydrase isozymes, showing the full affinity and selectivity profile. The structures of several compounds were determined by X-ray crystallography, and the binding mode in the active site of CA enzyme was shown.

PubMed: 35455474
DOI: 10.3390/ph15040477

実験手法

X-RAY DIFFRACTION (1.13 Å)