6H33

The crystal structure of human carbonic anhydrase II in complex with 4-(4-phenyl)-4-hydroxy-1-piperidine-1-carbonyl)benzenesulfonamide.

6H33 の概要

• エントリーDOI: 10.2210/pdb6h33/pdb
• 関連するPDBエントリー: 6H2Z
• 分子名称: Carbonic anhydrase 2, ZINC ION, 4-(4-oxidanyl-4-phenyl-piperidin-1-yl)carbonylbenzenesulfonamide, ... (5 entities in total)
• 機能のキーワード: protein-inhibitor binding, benzenesulfonamide, 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: 29995.24

構造登録者

Buemi, M.R.,Di Fiore, A.,De Luca, L.,Ferro, S.,Mancuso, F.,Monti, S.M.,Buonanno, M.,Angeli, A.,Russo, E.,De Sarro, G.,Supuran, C.T.,De Simone, G.,Gitto, R. (登録日: 2018-07-17, 公開日: 2018-12-19, 最終更新日: 2024-01-17)

主引用文献

Buemi, M.R.,Di Fiore, A.,De Luca, L.,Angeli, A.,Mancuso, F.,Ferro, S.,Monti, S.M.,Buonanno, M.,Russo, E.,De Sarro, G.,De Simone, G.,Supuran, C.T.,Gitto, R.
Exploring structural properties of potent human carbonic anhydrase inhibitors bearing a 4-(cycloalkylamino-1-carbonyl)benzenesulfonamide moiety.
Eur J Med Chem, 163:443-452, 2018

PubMed Abstract: Guided by the crystal structure of 4-(3,4-dihydroquinolin-1(2H)-ylcarbonyl)benzenesulfonamide 3 in complex with hCA II (PDB code 4Z0Q), a novel series of cycloalkylamino-1-carbonylbenzenesulfonamides was designed and synthesized. Thus, we replaced the quinoline ring with an azepine/piperidine/piperazine nucleus and introduced further modifications on cycloalkylamine nucleus by means the installation of hydrophobic/hydrophilic functionalities able to establish additional contacts in the middle area of the enzyme cavity. Among the synthesized compounds, the derivatives 7a, 7b, 8b exhibited a remarkable inhibition for hCA II and the brain-expressed hCA VII in subnanomolar range. The binding of these molecules to the target enzymes was characterized by means of a crystallographic analysis, providing a clear snapshot of the most important interactions established by this class of inhibitors into the hCA II and hCA VII catalytic site. Notably, our results showed that the benzylpiperazine tail of compound 8b is oriented both in hCA II and in hCA VII toward a poorly explored region of the active site. These features should be further investigated for the design of new isoform selective CA inhibitors.

PubMed: 30530195
DOI: 10.1016/j.ejmech.2018.11.073

実験手法

X-RAY DIFFRACTION (1.58 Å)