4x0w: Difference between revisions
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==The crystal structure of mupain-1-17 in complex with murinised human uPA== | ==The crystal structure of mupain-1-17 in complex with murinised human uPA== | ||
<StructureSection load='4x0w' size='340' side='right' caption='[[4x0w]], [[Resolution|resolution]] 2.10Å' scene=''> | <StructureSection load='4x0w' size='340' side='right'caption='[[4x0w]], [[Resolution|resolution]] 2.10Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[4x0w]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4X0W OCA]. For a <b>guided tour on the structure components</b> use [ | <table><tr><td colspan='2'>[[4x0w]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4X0W OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4X0W FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand= | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=DAL:D-ALANINE'>DAL</scene>, <scene name='pdbligand=MRZ:PIPERIDINE-1-CARBOXIMIDAMIDE'>MRZ</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=4x0w FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4x0w OCA], [https://pdbe.org/4x0w PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4x0w RCSB], [https://www.ebi.ac.uk/pdbsum/4x0w PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4x0w ProSAT]</span></td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | |||
</table> | </table> | ||
== Disease == | == Disease == | ||
[ | [https://www.uniprot.org/uniprot/UROK_HUMAN UROK_HUMAN] Defects in PLAU are the cause of Quebec platelet disorder (QPD) [MIM:[https://omim.org/entry/601709 601709]. QPD is an autosomal dominant bleeding disorder due to a gain-of-function defect in fibrinolysis. Although affected individuals do not exhibit systemic fibrinolysis, they show delayed onset bleeding after challenge, such as surgery. The hallmark of the disorder is markedly increased PLAU levels within platelets, which causes intraplatelet plasmin generation and secondary degradation of alpha-granule proteins.<ref>PMID:20007542</ref> | ||
== Function == | == Function == | ||
[ | [https://www.uniprot.org/uniprot/UROK_HUMAN UROK_HUMAN] Specifically cleaves the zymogen plasminogen to form the active enzyme plasmin. | ||
<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
== Publication Abstract from PubMed == | == Publication Abstract from PubMed == | ||
| Line 23: | Line 20: | ||
</div> | </div> | ||
<div class="pdbe-citations 4x0w" style="background-color:#fffaf0;"></div> | <div class="pdbe-citations 4x0w" style="background-color:#fffaf0;"></div> | ||
==See Also== | |||
*[[Plasminogen activator|Plasminogen activator]] | |||
*[[Urokinase 3D Structures|Urokinase 3D Structures]] | |||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: | [[Category: Homo sapiens]] | ||
[[Category: | [[Category: Large Structures]] | ||
[[Category: | [[Category: Synthetic construct]] | ||
[[Category: | [[Category: Andreasen P]] | ||
[[Category: Huang M]] | |||
[[Category: | [[Category: Jiang L]] | ||
[[Category: | [[Category: Xu P]] | ||
[[Category: | [[Category: Zhao B]] | ||
[[Category: | |||
Latest revision as of 00:06, 13 April 2023
The crystal structure of mupain-1-17 in complex with murinised human uPAThe crystal structure of mupain-1-17 in complex with murinised human uPA
Structural highlights
DiseaseUROK_HUMAN Defects in PLAU are the cause of Quebec platelet disorder (QPD) [MIM:601709. QPD is an autosomal dominant bleeding disorder due to a gain-of-function defect in fibrinolysis. Although affected individuals do not exhibit systemic fibrinolysis, they show delayed onset bleeding after challenge, such as surgery. The hallmark of the disorder is markedly increased PLAU levels within platelets, which causes intraplatelet plasmin generation and secondary degradation of alpha-granule proteins.[1] FunctionUROK_HUMAN Specifically cleaves the zymogen plasminogen to form the active enzyme plasmin. Publication Abstract from PubMedTwo isomeric piperidine derivatives (meta and para isomers) were used as arginine mimics in the P1 position of a cyclic peptidic inhibitor (CPAYSRYLDC) of urokinase-type plasminogen activator. The two resulting cyclic peptides showed vastly different affinities ( approximately 70 fold) to the target enzyme. X-ray crystal structure analysis showed that the two P1 residues were inserted into the S1 specificity pocket in indistinguishable manners. However, the rest of the peptides bound in entirely different ways on the surface of the enzyme, and the two peptides have different conformations, despite the highly similar sequence. These results demonstrate how the subtle difference in P1 residue can dictate the exosite interactions and the potencies of peptidic inhibitors, and highlight the importance of the P1 residue for protease inhibition. This study provides important information for the development of peptidic agents for pharmacological intervention. Distinctive binding modes and inhibitory mechanisms of two peptidic inhibitors of urokinase-type plasminogen activator with isomeric P1 residues.,Jiang L, Zhao B, Xu P, Sorensen HP, Jensen JK, Christensen A, Hosseini M, Nielsen NC, Jensen KJ, Andreasen PA, Huang M Int J Biochem Cell Biol. 2015 May;62:88-92. doi: 10.1016/j.biocel.2015.02.016., Epub 2015 Mar 2. PMID:25744057[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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