6RHK

The crystal structure of human carbonic anhydrase II in complex with 4-(3-benzylimidazolidine-1-carbonyl)benzenesulfonamide

6RHK の概要

• エントリーDOI: 10.2210/pdb6rhk/pdb
• 分子名称: Carbonic anhydrase 2, ZINC ION, 4-[3-(phenylmethyl)imidazolidin-1-yl]carbonylbenzenesulfonamide, ... (5 entities in total)
• 機能のキーワード: 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: 29884.08

構造登録者

Ferraroni, M.,Angeli, A.,Supuran, C.T. (登録日: 2019-04-22, 公開日: 2020-05-13, 最終更新日: 2024-01-24)

主引用文献

Chiaramonte, N.,Bua, S.,Angeli, A.,Ferraroni, M.,Picchioni, I.,Bartolucci, G.,Braconi, L.,Dei, S.,Teodori, E.,Supuran, C.T.,Romanelli, M.N.
Sulfonamides incorporating piperazine bioisosteres as potent human carbonic anhydrase I, II, IV and IX inhibitors.
Bioorg.Chem., 91:103130-103130, 2019

PubMed Abstract: Starting from the molecular simplification of (R) 4-(3,4-dibenzylpiperazine-1-carbonyl)benzenesulfonamide 9a, a compound endowed with selectivity for human Carbonic Anhydrase (hCA) IV, a series of piperazines and 4-aminopiperidines carrying a 4-sulfamoylbenzamide moiety as Zn-binding group have been designed and tested on human isoforms hCA I, II, IV and IX, using a stopped flow CO hydrase assay. The aim of the work was to derive structure-activity relationships useful for designing isoform selective compounds. These structural modifications changed the selectivity profile of the analogues from hCA IV to hCA I and II, and improved potency. Several of the new compounds showed subnanomolar activity on hCA II. X-ray crystallography of ligand-hCAII complexes was used to compare the binding modes of the new piperazines and the previously synthesized 2-benzyl-piperazine analogues, explaining the inhibition profiles.

PubMed: 31374520
DOI: 10.1016/j.bioorg.2019.103130

実験手法

X-RAY DIFFRACTION (1.44 Å)