8HID

HUMAN ERYTHROCYTE CATALSE COMPLEXED WITH BT-Br

8HID の概要

• エントリーDOI: 10.2210/pdb8hid/pdb
• 分子名称: Catalase, (~{S})-azanyl-[2-[[3-bromanyl-4-(diethylamino)phenyl]methyl]hydrazinyl]methanethiol, PROTOPORPHYRIN IX CONTAINING FE, ... (4 entities in total)
• 機能のキーワード: cytosolic protein-inhibitor complex, cytosolic protein/inhibitor
• 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: 243147.10

構造登録者

Lin, H.-Y.,Yang, G.-F. (登録日: 2022-11-19, 公開日: 2023-10-04)

主引用文献

Cao, Y.Y.,Chen, Y.Y.,Wang, M.S.,Tong, J.J.,Xu, M.,Zhao, C.,Lin, H.Y.,Mei, L.C.,Dong, J.,Zhang, W.L.,Qin, Y.X.,Huang, W.,Zhang, D.,Yang, G.F.
A catalase inhibitor: Targeting the NADPH-binding site for castration-resistant prostate cancer therapy.
Redox Biol, 63:102751-102751, 2023

PubMed Abstract: Catalase (CAT) is an important antioxidant enzyme that breaks down HO into water and oxygen. Inhibitor-modulating CAT activity in cancer cells is emerging as a potential anticancer strategy. However, the discovery of CAT inhibitors towards the heme active center located at the bottom of long and narrow channel has made little progress. Therefore, targeting new binding site is of great importance for the development of efficient CAT inhibitors. Here, the first NADPH-binding site inhibitor of CAT, BT-Br, was designed and synthesized successfully. The cocrystal structure of BT-Br-bound CAT complex was determined with a resolution of 2.2 Å (PDB ID:8HID), which showed clearly that BT-Br bound at the NADPH-binding site. Furthermore, BT-Br was demonstrated to induce ferroptosis in castration-resistant prostate cancer (CRPC) DU145 cells and eventually reduce CRPC tumors in vivo effectively. The work indicates that CAT has potential as a novel target for CRPC therapy based on ferroptosis inducing.

PubMed: 37216701
DOI: 10.1016/j.redox.2023.102751

実験手法

X-RAY DIFFRACTION (2.2 Å)