8Q1A

The Crystal Structure of Human Carbonic Anhydrase IX in Complex with inhibitor

8Q1A の概要

• エントリーDOI: 10.2210/pdb8q1a/pdb
• 分子名称: Carbonic anhydrase 9, ZINC ION, 1,1,3-tris(oxidanylidene)-2-pentyl-1,2-benzothiazole-6-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: 114706.44

構造登録者

Leitans, J.,Tars, K. (登録日: 2023-07-31, 公開日: 2023-11-08, 最終更新日: 2024-11-06)

主引用文献

Leitans, J.,Kazaks, A.,Bogans, J.,Supuran, C.T.,Akopjana, I.,Ivanova, J.,Zalubovskis, R.,Tars, K.
Structural Basis of Saccharin Derivative Inhibition of Carbonic Anhydrase IX.
Chemmedchem, 18:e202300454-e202300454, 2023

PubMed Abstract: This study explores the binding mechanisms of saccharin derivatives with human carbonic anhydrase IX (hCA IX), an antitumor drug target, with the aim of facilitating the design of potent and selective inhibitors. Through the use of crystallographic analysis, we investigate the structures of hCA IX-saccharin derivative complexes, unveiling their unique binding modes that exhibit both similarities to sulfonamides and distinct orientations of the ligand tail. Our comprehensive structural insights provide information regarding the crucial interactions between the ligands and the protein, shedding light on interactions that dictate inhibitor binding and selectivity. Through a comparative analysis of the binding modes observed in hCA II and hCA IX, isoform-specific interactions are identified, offering promising strategies for the development of isoform-selective inhibitors that specifically target tumor-associated hCA IX. The findings of this study significantly deepen our understanding of the binding mechanisms of hCA inhibitors, laying a solid foundation for the rational design of more effective inhibitors.

PubMed: 37837260
DOI: 10.1002/cmdc.202300454

実験手法

X-RAY DIFFRACTION (2.35 Å)