7NC4

Crystal structure of human carbonic anhydrase VII (hCA VII) in complex with a 4-(4-aroylpiperazine-1-carbonyl)benzenesulfonamide derivative.

7NC4 の概要

• エントリーDOI: 10.2210/pdb7nc4/pdb
• 分子名称: Carbonic anhydrase 7, ZINC ION, 4-[4-(2-chlorophenyl)carbonylpiperazin-1-yl]carbonylbenzenesulfonamide, ... (5 entities in total)
• 機能のキーワード: protein-inhibitor adduct, 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: 31583.16

構造登録者

Di Fiore, A.,De Simone, G. (登録日: 2021-01-28, 公開日: 2021-07-14, 最終更新日: 2024-11-13)

主引用文献

Mancuso, F.,Di Fiore, A.,De Luca, L.,Angeli, A.,De Simone, G.,Supuran, C.T.,Gitto, R.
Design, synthesis and biochemical evaluation of novel carbonic anhydrase inhibitors triggered by structural knowledge on hCA VII.
Bioorg.Med.Chem., 44:116279-116279, 2021

PubMed Abstract: To tackle the challenge of isoform selectivity, we explored the entrance of the cavity for selected druggable human Carbonic Anhydrases (hCAs). Based on X-ray crystallographic studies on the 4-(4-(2-chlorobenzoyl)piperazine-1-carbonyl)benzenesulfonamide in complex with the brain expressed hCA VII (PDB code: 7NC4), a series of 4-(4(hetero)aroylpiperazine-1-carbonyl)benzene-1-sulfonamides has been developed. To evaluate their capability to fit the hCA VII catalytic cavity, the newer benzenesulfonamides were preliminary investigated by means of docking simulations. Then, this series of thirteen benzenesulfonamides was synthesized and tested against selected druggable hCAs. Among them, the 4-(4-(furan-2-carbonyl)piperazine-1-carbonyl)benzenesulfonamide showed remarkable affinity towards hCA VII (K: 4.3 nM) and good selectivity over the physiologically widespread hCA I when compared to Topiramate (TPM).

PubMed: 34216985
DOI: 10.1016/j.bmc.2021.116279

実験手法

X-RAY DIFFRACTION (1.6 Å)