6EVR

Crystal structure of human carbonic anhydrase I in complex with the 4-(4 acetyl-3-benzylpiperazine-1 carbonyl)benzene-1-sulfonamide inhibitor

6EVR の概要

• エントリーDOI: 10.2210/pdb6evr/pdb
• 分子名称: Carbonic anhydrase 1, ZINC ION, 4-[(3~{S})-4-ethanoyl-3-(phenylmethyl)piperazin-1-yl]carbonylbenzenesulfonamide, ... (6 entities in total)
• 機能のキーワード: inhibitor, complex, lyase
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 58989.38

構造登録者

Ferraroni, M.,Supuran, C.T.,Chiapponi, D.,Chiaramonte, N. (登録日: 2017-11-02, 公開日: 2018-06-06, 最終更新日: 2024-01-17)

主引用文献

Chiaramonte, N.,Bua, S.,Ferraroni, M.,Nocentini, A.,Bonardi, A.,Bartolucci, G.,Durante, M.,Lucarini, L.,Chiapponi, D.,Dei, S.,Manetti, D.,Teodori, E.,Gratteri, P.,Masini, E.,Supuran, C.T.,Romanelli, M.N.
2-Benzylpiperazine: A new scaffold for potent human carbonic anhydrase inhibitors. Synthesis, enzyme inhibition, enantioselectivity, computational and crystallographic studies and in vivo activity for a new class of intraocular pressure lowering agents.
Eur J Med Chem, 151:363-375, 2018

PubMed Abstract: Two series of 2-benzylpiperazines have been prepared and tested for the inhibition of physiologically relevant isoforms of human carbonic anhydrases (hCA, EC 4.2.1.1). The new compounds carry on one nitrogen atom of the piperazine ring a sulfamoylbenzamide group as zinc-binding moiety, and different alkyl/acyl/sulfonyl groups on the other nitrogen. Regio- and stero-isomers are described. The majority of these compounds showed Ki values in the low-medium nanomolar range against hCA I, II and IV, but not IX. In many instances interaction with the enzyme was enantioselective. The binding mode has been studied by means of X-ray crystallography and molecular modelling. Two compounds, evaluated in rabbit models of glaucoma, were able to significantly reduce intraocular pressure, making them interesting candidates for further studies.

PubMed: 29635168
DOI: 10.1016/j.ejmech.2018.04.002

実験手法

X-RAY DIFFRACTION (1.5 Å)