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1f5l

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Revision as of 15:09, 3 November 2021

UROKINASE PLASMINOGEN ACTIVATOR B-CHAIN-AMILORIDE COMPLEX

Structural highlights

1f5l 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:	1ejn, 1f5k, 1f92
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.

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 is a serine protease involved in cancer growth and metastasis. Here we present the first urokinase crystal structure in complex with reversible inhibitors at 2.1 and 2.6 A resolution. These inhibitor complex structures have been obtained from crystals of engineered urokinase type plasminogen activator designed to obtain a crystal form open for inhibitor soaking. The mutant C122S loses its flexible A-chain upon activation cleavage and crystallizes in the presence of benzamidine, which was later displaced by the desired inhibitor. This new soakable crystal form turned out to be of great value in the process of structure-based drug design. The evaluated binding mode of amiloride, and UKI-1D revealed a new subsite of the primary specificity pocket of urokinase that will be employed in the future ligand optimisation process.

Crystals of the urokinase type plasminogen activator variant beta(c)-uPAin complex with small molecule inhibitors open the way towards structure-based drug design.,Zeslawska E, Schweinitz A, Karcher A, Sondermann P, Sperl S, Sturzebecher J, Jacob U J Mol Biol. 2000 Aug 11;301(2):465-75. PMID:10926521^[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, Schweinitz A, Karcher A, Sondermann P, Sperl S, Sturzebecher J, Jacob U. Crystals of the urokinase type plasminogen activator variant beta(c)-uPAin complex with small molecule inhibitors open the way towards structure-based drug design. J Mol Biol. 2000 Aug 11;301(2):465-75. PMID:10926521 doi:http://dx.doi.org/10.1006/jmbi.2000.3966

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/1f5l"

@@ Line 3: / Line 3: @@
 <StructureSection load='1f5l' size='340' side='right'caption='[[1f5l]], [[Resolution|resolution]] 2.10&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[1f5l]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1F5L OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1F5L FirstGlance]. <br>
+<table><tr><td colspan='2'>[[1f5l]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1F5L OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1F5L FirstGlance]. <br>
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=AMR:3,5-DIAMINO-N-(AMINOIMINOMETHYL)-6-CHLOROPYRAZINECARBOXAMIDE'>AMR</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"><div style='overflow: auto; max-height: 3em;'>[[1ejn|1ejn]], [[1f5k|1f5k]], [[1f92|1f92]]</div></td></tr>
@@ Line 39: / Line 39: @@
 __TOC__
 </StructureSection>
+[[Category: Human]]
 [[Category: Large Structures]]
 [[Category: U-plasminogen activator]]
@@ Line 48: / Line 49: @@
 [[Category: Sturzebecher, J]]
 [[Category: Zeslawska, E]]
-[[Category: Human]]
 [[Category: Hydrolase]]
 [[Category: Inhibitor]]
 [[Category: Serine protease]]
 [[Category: Urokinase]]

1f5l

From Proteopedia

Revision as of 15:09, 3 November 2021

UROKINASE PLASMINOGEN ACTIVATOR B-CHAIN-AMILORIDE COMPLEX

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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