4os5: Difference between revisions
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==Crystal structure of urokinase-type plasminogen activator (uPA) complexed with bicyclic peptide UK603 (bicyclic 2)== | ==Crystal structure of urokinase-type plasminogen activator (uPA) complexed with bicyclic peptide UK603 (bicyclic 2)== | ||
<StructureSection load='4os5' size='340' side='right' caption='[[4os5]], [[Resolution|resolution]] 2.26Å' scene=''> | <StructureSection load='4os5' size='340' side='right'caption='[[4os5]], [[Resolution|resolution]] 2.26Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[4os5]] is a 2 chain structure with sequence from [ | <table><tr><td colspan='2'>[[4os5]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4OS5 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4OS5 FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=81R:(4R)-4,5-DISULFANYL-L-NORVALINE'>81R</scene>, <scene name='pdbligand=NH2:AMINO+GROUP'>NH2</scene>, <scene name='pdbligand=PRD_001227:bicyclic+peptide+UK603+(bicyclic+2)'>PRD_001227</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=4os5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4os5 OCA], [https://pdbe.org/4os5 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4os5 RCSB], [https://www.ebi.ac.uk/pdbsum/4os5 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4os5 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 24: | Line 20: | ||
</div> | </div> | ||
<div class="pdbe-citations 4os5" style="background-color:#fffaf0;"></div> | <div class="pdbe-citations 4os5" 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: Chen | [[Category: Chen S]] | ||
[[Category: Heinis | [[Category: Heinis C]] | ||
[[Category: Pojer | [[Category: Pojer F]] | ||
Latest revision as of 11:19, 8 March 2023
Crystal structure of urokinase-type plasminogen activator (uPA) complexed with bicyclic peptide UK603 (bicyclic 2)Crystal structure of urokinase-type plasminogen activator (uPA) complexed with bicyclic peptide UK603 (bicyclic 2)
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 PubMedThe disulfide bonds that form between two cysteine residues are important in defining and rigidifying the structures of proteins and peptides. In polypeptides containing multiple cysteine residues, disulfide isomerization can lead to multiple products with different biological activities. Here, we describe the development of a dithiol amino acid (Dtaa) that can form two disulfide bridges at a single amino acid site. Application of Dtaas to a serine protease inhibitor and a nicotinic acetylcholine receptor inhibitor that contain disulfide constraints enhanced their inhibitory activities 40- and 7.6-fold, respectively. X-ray crystallographic and NMR structure analysis show that the peptide ligands containing Dtaas have retained their native tertiary structures. We furthermore show that replacement of two cysteines by Dtaas can avoid the formation of disulfide bond isomers. With these properties, Dtaas are likely to have broad application in the rational design or directed evolution of peptides and proteins with high activity and stability. Dithiol amino acids can structurally shape and enhance the ligand-binding properties of polypeptides.,Chen S, Gopalakrishnan R, Schaer T, Marger F, Hovius R, Bertrand D, Pojer F, Heinis C Nat Chem. 2014 Nov;6(11):1009-16. doi: 10.1038/nchem.2043. Epub 2014 Aug 31. PMID:25343607[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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