6A8N
The crystal structure of muPAin-1-IG-2 in complex with muPA-SPD at pH8.5
Summary for 6A8N
| Entry DOI | 10.2210/pdb6a8n/pdb |
| Descriptor | Urokinase-type plasminogen activator B, CYS-PRO-ALA-TYR-SER-ARG-TYR-ILE-GLY-CYS (2 entities in total) |
| Functional Keywords | peptides inhibitor, mupa, serine protease, hydrolase, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor |
| Biological source | Mus musculus (Mouse) More |
| Total number of polymer chains | 4 |
| Total formula weight | 57374.96 |
| Authors | Wang, D.,Yang, Y.S.,Jiang, L.G.,Huang, M.D.,Li, J.Y.,Andreasen, P.A.,Xu, P.,Chen, Z. (deposition date: 2018-07-09, release date: 2019-02-20, Last modification date: 2024-10-23) |
| Primary citation | 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 Cited by 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: 30707839DOI: 10.1021/acs.jmedchem.8b01908 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.489 Å) |
Structure validation
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