5BYI

Human carbonic anhydrase II with an azobenzene inhibitor (1d)

5BYI の概要

• エントリーDOI: 10.2210/pdb5byi/pdb
• 関連するPDBエントリー: 2VVA
• 分子名称: Carbonic anhydrase 2, ZINC ION, 4-(HYDROXYMERCURY)BENZOIC ACID, ... (6 entities in total)
• 機能のキーワード: carbonic anhydrase, sulfonamide, photopharmacology, inhibitor, 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: 30047.69

構造登録者

Groll, M.,Broichhagen, J. (登録日: 2015-06-10, 公開日: 2015-08-05, 最終更新日: 2024-05-08)

主引用文献

Runtsch, L.S.,Barber, D.M.,Mayer, P.,Groll, M.,Trauner, D.,Broichhagen, J.
Azobenzene-based inhibitors of human carbonic anhydrase II.
Beilstein J Org Chem, 11:1129-1135, 2015

PubMed Abstract: Aryl sulfonamides are a widely used drug class for the inhibition of carbonic anhydrases. In the context of our program of photochromic pharmacophores we were interested in the exploration of azobenzene-containing sulfonamides to block the catalytic activity of human carbonic anhydrase II (hCAII). Herein, we report the synthesis and in vitro evaluation of a small library of nine photochromic sulfonamides towards hCAII. All molecules are azobenzene-4-sulfonamides, which are substituted by different functional groups in the 4´-position and were characterized by X-ray crystallography. We aimed to investigate the influence of electron-donating or electron-withdrawing substituents on the inhibitory constant K i. With the aid of an hCAII crystal structure bound to one of the synthesized azobenzenes, we found that the electronic structure does not strongly affect inhibition. Taken together, all compounds are strong blockers of hCAII with K i = 25-65 nM that are potentially photochromic and thus combine studies from chemical synthesis, crystallography and enzyme kinetics.

PubMed: 26199669
DOI: 10.3762/bjoc.11.127

実験手法

X-RAY DIFFRACTION (1.15 Å)