8CO0

Three dimensional structure of human carbonic anhydrase IX in complex with sulfonamide

8CO0 の概要

• エントリーDOI: 10.2210/pdb8co0/pdb
• 分子名称: Carbonic anhydrase 9, ZINC ION, 5-(5-methyl-6-quinolin-5-yl-pyridin-3-yl)thiophene-2-sulfonamide, ... (5 entities in total)
• 機能のキーワード: ca ix, ca 9, carbonic anhydrase ix, carbonic anhydrase 9, lyase
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 114902.74

構造登録者

Leitans, J.,Tars, K. (登録日: 2023-02-25, 公開日: 2023-12-13, 最終更新日: 2024-11-20)

主引用文献

Ivanova, J.N.,Nocentini, A.,Tars, K.,Leita Ns, J.N.,Dvinskis, E.,Kazaks, A.,Domraceva, I.,Supuran, C.T.,Zalubovskis, R.
Atropo/Tropo Flexibility: A Tool for Design and Synthesis of Self-Adaptable Inhibitors of Carbonic Anhydrases and Their Antiproliferative Effect.
J.Med.Chem., 66:5703-5718, 2023

PubMed Abstract: Here, we report for the first time a series of sulfonamide derivatives with scaffolds bearing flexible moieties, namely, rotamers or tropoisomers capable of adapting their geometry in the active center of enzymes thus being effective and selective carbonic anhydrase (CAs, EC 4.2.1.1) enzyme inhibitors. All compounds exhibited effective in vitro inhibition activity toward the main hCA isoforms related to cancer (i.e., hCA II, hCA IX, and hCA XII with values in the low nanomolar range). Three selected compounds showed a great cytotoxic effect on cancer cell lines ex vivo. X-ray crystallographic experiments assessed the binding modes of compound with active centers of hCA IX and hCA XII.

PubMed: 37022308
DOI: 10.1021/acs.jmedchem.3c00007

実験手法

X-RAY DIFFRACTION (2.3 Å)