4RIV

A Carbonic Anhydrase IX Mimic in Complex with Saccharin

4RIV の概要

• エントリーDOI: 10.2210/pdb4riv/pdb
• 関連するPDBエントリー: 4RIU
• 分子名称: Carbonic anhydrase 2, ZINC ION, 1,2-BENZISOTHIAZOL-3(2H)-ONE 1,1-DIOXIDE, ... (5 entities in total)
• 機能のキーワード: carbonic anhydrase fold, reversible hydration of co2, active site point mutations, cytosolic, 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: 29724.76

構造登録者

Mahon, B.P.,McKenna, R. (登録日: 2014-10-07, 公開日: 2015-02-04, 最終更新日: 2023-09-20)

主引用文献

Mahon, B.P.,Hendon, A.M.,Driscoll, J.M.,Rankin, G.M.,Poulsen, S.A.,Supuran, C.T.,McKenna, R.
Saccharin: A lead compound for structure-based drug design of carbonic anhydrase IX inhibitors.
Bioorg.Med.Chem., 23:849-854, 2015

PubMed Abstract: Carbonic anhydrase IX (CA IX) is a key modulator of aggressive tumor behavior and a prognostic marker and target for several cancers. Saccharin (SAC) based compounds may provide an avenue to overcome CA isoform specificity, as they display both nanomolar affinity and preferential binding, for CA IX compared to CA II (>50-fold for SAC and >1000-fold when SAC is conjugated to a carbohydrate moiety). The X-ray crystal structures of SAC and a SAC-carbohydrate conjugate bound to a CA IX-mimic are presented and compared to CA II. The structures provide substantial new insight into the mechanism of SAC selective CA isoform inhibition.

PubMed: 25614109
DOI: 10.1016/j.bmc.2014.12.030

実験手法

X-RAY DIFFRACTION (1.631 Å)