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==The crystal structure of muPAin-1-IG in complex with muPA-SPD at pH8.5== | ==The crystal structure of muPAin-1-IG in complex with muPA-SPD at pH8.5== | ||
<StructureSection load='6a8g' size='340' side='right' caption='[[6a8g]], [[Resolution|resolution]] 2.53Å' scene=''> | <StructureSection load='6a8g' size='340' side='right'caption='[[6a8g]], [[Resolution|resolution]] 2.53Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[6a8g]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6A8G OCA]. For a <b>guided tour on the structure components</b> use [ | <table><tr><td colspan='2'>[[6a8g]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus] and [https://en.wikipedia.org/wiki/Phage_display_vector_pTDisp Phage display vector pTDisp]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6A8G OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6A8G FirstGlance]. <br> | ||
</td></tr><tr id=' | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.53Å</td></tr> | ||
<tr id=' | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACE:ACETYL+GROUP'>ACE</scene>, <scene name='pdbligand=NH2:AMINO+GROUP'>NH2</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene></td></tr> | ||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=6a8g FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6a8g OCA], [https://pdbe.org/6a8g PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6a8g RCSB], [https://www.ebi.ac.uk/pdbsum/6a8g PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6a8g ProSAT]</span></td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | |||
</table> | </table> | ||
== Function == | == Function == | ||
[ | [https://www.uniprot.org/uniprot/UROK_MOUSE UROK_MOUSE] Specifically cleaves the zymogen plasminogen to form the active enzyme plasmin. | ||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
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. | |||
Suppression of Tumor Growth and Metastases by Targeted Intervention in Urokinase Activity with Cyclic Peptides.,Wang D, Yang Y, Jiang L, Wang Y, Li J, Andreasen PA, Chen Z, Huang M, Xu P J Med Chem. 2019 Feb 28;62(4):2172-2183. doi: 10.1021/acs.jmedchem.8b01908. Epub , 2019 Feb 15. PMID:30707839<ref>PMID:30707839</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 6a8g" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Urokinase 3D Structures|Urokinase 3D Structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: | [[Category: Large Structures]] | ||
[[Category: | [[Category: Mus musculus]] | ||
[[Category: | [[Category: Phage display vector pTDisp]] | ||
[[Category: | [[Category: Andreasen PA]] | ||
[[Category: | [[Category: Chen Z]] | ||
[[Category: | [[Category: Huang MD]] | ||
[[Category: | [[Category: Jiang LG]] | ||
[[Category: | [[Category: Li JY]] | ||
[[Category: | [[Category: Wang D]] | ||
[[Category: | [[Category: Xu P]] | ||
[[Category: | [[Category: Yang YS]] | ||
Latest revision as of 12:21, 22 November 2023
The crystal structure of muPAin-1-IG in complex with muPA-SPD at pH8.5The crystal structure of muPAin-1-IG in complex with muPA-SPD at pH8.5
Structural highlights
FunctionUROK_MOUSE Specifically cleaves the zymogen plasminogen to form the active enzyme plasmin. Publication Abstract from PubMedUrokinase-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. Suppression of Tumor Growth and Metastases by Targeted Intervention in Urokinase Activity with Cyclic Peptides.,Wang D, Yang Y, Jiang L, Wang Y, Li J, Andreasen PA, Chen Z, Huang M, Xu P J Med Chem. 2019 Feb 28;62(4):2172-2183. doi: 10.1021/acs.jmedchem.8b01908. Epub , 2019 Feb 15. PMID:30707839[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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