6FE2

Three dimensional structure of human carbonic anhydrase IX

6FE2 の概要

• エントリーDOI: 10.2210/pdb6fe2/pdb
• 分子名称: Carbonic anhydrase 9, ZINC ION (3 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: 4
• 化学式量合計: 112952.37

構造登録者

Leitans, J.,Tars, K. (登録日: 2017-12-28, 公開日: 2018-07-04, 最終更新日: 2024-11-06)

主引用文献

Kazokaite, J.,Niemans, R.,Dudutiene, V.,Becker, H.M.,Leitans, J.,Zubriene, A.,Baranauskiene, L.,Gondi, G.,Zeidler, R.,Matuliene, J.,Tars, K.,Yaromina, A.,Lambin, P.,Dubois, L.J.,Matulis, D.
Novel fluorinated carbonic anhydrase IX inhibitors reduce hypoxia-induced acidification and clonogenic survival of cancer cells.
Oncotarget, 9:26800-26816, 2018

PubMed Abstract: Human carbonic anhydrase (CA) IX has emerged as a promising anticancer target and a diagnostic biomarker for solid hypoxic tumors. Novel fluorinated CA IX inhibitors exhibited up to 50 pM affinity towards the recombinant human CA IX, selectivity over other CAs, and direct binding to Zn(II) in the active site of CA IX inducing novel conformational changes as determined by X-ray crystallography. Mass spectrometric gas-analysis confirmed the CA IX-based mechanism of the inhibitors in a CRISPR/Cas9-mediated CA IX knockout in HeLa cells. Hypoxia-induced extracellular acidification was significantly reduced in HeLa, H460, MDA-MB-231, and A549 cells exposed to the compounds, with the values up to 1.29 nM. A decreased clonogenic survival was observed when hypoxic H460 3D spheroids were incubated with our lead compound. These novel compounds are therefore promising agents for CA IX-specific therapy.

PubMed: 29928486
DOI: 10.18632/oncotarget.25508

実験手法

X-RAY DIFFRACTION (1.87 Å)