6A8G

The crystal structure of muPAin-1-IG in complex with muPA-SPD at pH8.5

6A8G の概要

• エントリーDOI: 10.2210/pdb6a8g/pdb
• 分子名称: muPAin-1-IG, Urokinase-type plasminogen activator chain B, PHOSPHATE ION, ... (4 entities in total)
• 機能のキーワード: peptides inhibitor, mupa, serine protease, hydrolase, hydrolase inhibitor-hydrolase complex, hydrolase inhibitor/hydrolase
• 由来する生物種: Mus musculus (Mouse); 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 57897.91

構造登録者

Wang, D.,Yang, Y.S.,Jiang, L.G.,Huang, M.D.,Li, J.Y.,Andreasen, P.A.,Xu, P.,Chen, Z. (登録日: 2018-07-08, 公開日: 2019-02-20, 最終更新日: 2024-10-16)

主引用文献

Wang, D.,Yang, Y.,Jiang, L.,Wang, Y.,Li, J.,Andreasen, P.A.,Chen, Z.,Huang, M.,Xu, P.
Suppression of Tumor Growth and Metastases by Targeted Intervention in Urokinase Activity with Cyclic Peptides.
J.Med.Chem., 62:2172-2183, 2019

PubMed Abstract: Urokinase-type plasminogen activator (uPA) is a diagnostic marker for breast and prostate cancers recommended by American Society for Clinical Oncology and German Breast Cancer Society. Inhibition of uPA was proposed as an efficient strategy for cancer treatments. In this study, we report peptide-based uPA inhibitors with high potency and specificity comparable to monoclonal antibodies. We revealed the binding and inhibitory mechanisms by combining crystallography, molecular dynamic simulation, and other biophysical and biochemical approaches. Besides, we showed that our peptides efficiently inhibited the invasion of cancer cells via intervening with the processes of the degradation of extracellular matrices. Furthermore, our peptides significantly suppressed the tumor growth and the cancer metastases in tumor-bearing mice. This study demonstrates that these uPA peptides are highly potent anticancer agents and reveals the mechanistic insights of these uPA inhibitors, which can be useful for developing other serine protease inhibitors.

PubMed: 30707839
DOI: 10.1021/acs.jmedchem.8b01908

実験手法

X-RAY DIFFRACTION (2.53 Å)