5E28

Crystal structure of human carbonic anhydrase II in complex with the 4-(4-aminophenyl)benzenesulfonamide inhibitor

5E28 の概要

• エントリーDOI: 10.2210/pdb5e28/pdb
• 分子名称: Carbonic anhydrase 2, ZINC ION, 4'-aminobiphenyl-4-sulfonamide, ... (5 entities in total)
• 機能のキーワード: 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: 29338.44

構造登録者

Ferraroni, M.,Supuran, C.T. (登録日: 2015-09-30, 公開日: 2016-01-20, 最終更新日: 2024-01-10)

主引用文献

Cornelio, B.,Laronze-Cochard, M.,Ceruso, M.,Ferraroni, M.,Rance, G.A.,Carta, F.,Khlobystov, A.N.,Fontana, A.,Supuran, C.T.,Sapi, J.
4-Arylbenzenesulfonamides as Human Carbonic Anhydrase Inhibitors (hCAIs): Synthesis by Pd Nanocatalyst-Mediated Suzuki-Miyaura Reaction, Enzyme Inhibition, and X-ray Crystallographic Studies.
J.Med.Chem., 59:721-732, 2016

PubMed Abstract: Benzenesulfonamides bearing various substituted (hetero)aryl rings in the para-position were prepared by palladium nanoparticle-catalyzed Suzuki-Miyaura cross-coupling reactions and evaluated as human carbonic anhydrase (hCA, EC 4.2.1.1) inhibitors against isoforms hCA I, II, IX, and XII. Most of the prepared sulfonamides showed low inhibition against hCA I isoform, whereas the other cytosolic isoenzyme, hCA II, was strongly affected. The major part of these new derivatives acted as potent inhibitors of the tumor-associated isoform hCA XII. An opposite trend was observed for phenyl, naphthyl, and various heteroaryl substituted benzenesulfonamides which displayed subnanomolar hCA IX inhibition while poorly inhibiting the other tumor-associated isoform hCA XII. The inhibition potency and influence of the partially restricted aryl-aryl bond rotation on the activity/selectivity were rationalized by means of X-ray crystallography of the adducts of hCA II with several 4-arylbenzenesulfonamides.

PubMed: 26741028
DOI: 10.1021/acs.jmedchem.5b01771

実験手法

X-RAY DIFFRACTION (1.3 Å)