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1w10

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Revision as of 16:46, 10 September 2015

UROKINASE TYPE PLASMINOGEN ACTIVATOR

Structural highlights

1w10 is a 1 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	,
Related:	1c5w, 1c5x, 1c5y, 1c5z, 1ejn, 1f5k, 1f5l, 1f92, 1fv9, 1gi7, 1gi8, 1gi9, 1gj7, 1gj8, 1gj9, 1gja, 1gjb, 1gjc, 1gjd, 1kdu, 1lmw, 1o3p, 1owd, 1owe, 1owh, 1owi, 1owj, 1owk, 1sqa, 1sqo, 1sqt, 1urk, 1w0z, 1w11, 1w12, 1w13, 1w14
Activity:	U-plasminogen activator, with EC number 3.4.21.73
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum

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.

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

Urokinase type plasminogen activator (uPA), a trypsin-like serine proteinase, plays an important role in normal tissue re-modelling, cell adhesion, and cell motility. In addition, studies utilizing normal animals and potent, selective uPA inhibitors or genetically modified mice that lack functional uPA genes have demonstrated that uPA can significantly enhance tumor initiation, growth, progression and metastasis, strongly suggesting that this enzyme may be a promising anti-cancer target. We have investigated the structure-activity relationship (SAR) of peptidomimetic inhibitors of uPA and solved high resolution X-ray structures of key, lead small molecule inhibitors (e.g. phenethylsulfonamidino(P4)-D-seryl(P3)-L-alanyl(P2)-L-argininal(P1) and derivatives thereof) in complex with the uPA proteinase domain. These potent inhibitors are highly selective for uPA. The non-natural D-seryl residue present at the P3 position in these inhibitors contributes substantially to both potency and selectivity because, due to its D-configuration, its side-chain binds in the S4 pocket to interact with the uPA unique residues Leu97b and His99. Additional potency and selectivity can be achieved by optimizing the inhibitor P4 residue to bind a pocket, known as S1sub or S1beta, that is adjacent to the primary specificity pocket of uPA.

Crystals of urokinase type plasminogen activator complexes reveal the binding mode of peptidomimetic inhibitors.,Zeslawska E, Jacob U, Schweinitz A, Coombs G, Bode W, Madison E J Mol Biol. 2003 Apr 18;328(1):109-18. PMID:12684001^[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
↑ Zeslawska E, Jacob U, Schweinitz A, Coombs G, Bode W, Madison E. Crystals of urokinase type plasminogen activator complexes reveal the binding mode of peptidomimetic inhibitors. J Mol Biol. 2003 Apr 18;328(1):109-18. PMID:12684001

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/1w10"

@@ Line 2: / Line 2: @@
 <StructureSection load='1w10' size='340' side='right' caption='[[1w10]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[1w10]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1W10 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1W10 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[1w10]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1W10 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1W10 FirstGlance]. <br>
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=SJ1:N-(ISOBUTOXYCARBONYL)-D-SERYL-N-((1S)-4-{[AMINO(IMINO)METHYL]AMINO}-1-FORMYLBUTYL)-L-ALANINAMIDE'>SJ1</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1c5w|1c5w]], [[1c5x|1c5x]], [[1c5y|1c5y]], [[1c5z|1c5z]], [[1ejn|1ejn]], [[1f5k|1f5k]], [[1f5l|1f5l]], [[1f92|1f92]], [[1fv9|1fv9]], [[1gi7|1gi7]], [[1gi8|1gi8]], [[1gi9|1gi9]], [[1gj7|1gj7]], [[1gj8|1gj8]], [[1gj9|1gj9]], [[1gja|1gja]], [[1gjb|1gjb]], [[1gjc|1gjc]], [[1gjd|1gjd]], [[1kdu|1kdu]], [[1lmw|1lmw]], [[1o3p|1o3p]], [[1owd|1owd]], [[1owe|1owe]], [[1owh|1owh]], [[1owi|1owi]], [[1owj|1owj]], [[1owk|1owk]], [[1sqa|1sqa]], [[1sqo|1sqo]], [[1sqt|1sqt]], [[1urk|1urk]], [[1w0z|1w0z]], [[1w11|1w11]], [[1w12|1w12]], [[1w13|1w13]], [[1w14|1w14]]</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=1w10 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1w10 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1w10 RCSB], [http://www.ebi.ac.uk/pdbsum/1w10 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=1w10 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1w10 OCA], [http://pdbe.org/1w10 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1w10 RCSB], [http://www.ebi.ac.uk/pdbsum/1w10 PDBsum]</span></td></tr>
 </table>
 == Disease ==
@@ Line 30: / Line 30: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 1w10" style="background-color:#fffaf0;"></div>
 ==See Also==
@@ Line 37: / Line 38: @@
 __TOC__
 </StructureSection>
-[[Category: Homo sapiens]]
+[[Category: Human]]
 [[Category: U-plasminogen activator]]
 [[Category: Jacob, U]]

1w10

From Proteopedia

Revision as of 16:46, 10 September 2015

UROKINASE TYPE PLASMINOGEN ACTIVATOR

Structural highlights

Disease

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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