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4os7

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Revision as of 14:11, 11 August 2016

Crystal structure of urokinase-type plasminogen activator (uPA) complexed with bicyclic peptide UK607 (bicyclic)

Structural highlights

4os7 is a 2 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	, ,
NonStd Res:	,
Related:	4gly, 4os1, 4os2, 4os4, 4os5, 4os6
Activity:	U-plasminogen activator, with EC number 3.4.21.73
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

[UROK_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]

Function

[UROK_HUMAN] Specifically cleaves the zymogen plasminogen to form the active enzyme plasmin.

Publication Abstract from PubMed

The 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.

References

↑ Paterson AD, Rommens JM, Bharaj B, Blavignac J, Wong I, Diamandis M, Waye JS, Rivard GE, Hayward CP. Persons with Quebec platelet disorder have a tandem duplication of PLAU, the urokinase plasminogen activator gene. Blood. 2010 Feb 11;115(6):1264-6. doi: 10.1182/blood-2009-07-233965. Epub 2009, Dec 9. PMID:20007542 doi:10.1182/blood-2009-07-233965
↑ Chen S, Gopalakrishnan R, Schaer T, Marger F, Hovius R, Bertrand D, Pojer F, Heinis C. Dithiol amino acids can structurally shape and enhance the ligand-binding properties of polypeptides. Nat Chem. 2014 Nov;6(11):1009-16. doi: 10.1038/nchem.2043. Epub 2014 Aug 31. PMID:25343607 doi:http://dx.doi.org/10.1038/nchem.2043

1 Structural highlights
2 Disease
3 Function
4 Publication Abstract from PubMed
5 See Also
6 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4os7"

@@ Line 1: / Line 1: @@
 ==Crystal structure of urokinase-type plasminogen activator (uPA) complexed with bicyclic peptide UK607 (bicyclic)==
 <StructureSection load='4os7' size='340' side='right' caption='[[4os7]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
@@ Line 7: / Line 8: @@
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4gly|4gly]], [[4os1|4os1]], [[4os2|4os2]], [[4os4|4os4]], [[4os5|4os5]], [[4os6|4os6]]</td></tr>
 <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/U-plasminogen_activator U-plasminogen activator], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.21.73 3.4.21.73] </span></td></tr>
-<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4os7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4os7 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4os7 RCSB], [http://www.ebi.ac.uk/pdbsum/4os7 PDBsum]</span></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4os7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4os7 OCA], [http://pdbe.org/4os7 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4os7 RCSB], [http://www.ebi.ac.uk/pdbsum/4os7 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4os7 ProSAT]</span></td></tr>
 </table>
 == Disease ==
@@ Line 21: / Line 22: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 4os7" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Urokinase|Urokinase]]
 == References ==
 <references/>

4os7

From Proteopedia

Revision as of 14:11, 11 August 2016

Crystal structure of urokinase-type plasminogen activator (uPA) complexed with bicyclic peptide UK607 (bicyclic)

Structural highlights

Disease

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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