| Structural highlights
1sqa is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Ligands: | ,
| | Related: | 1owd, 1owe, 1owh, 1owi, 1owj, 1owk, 1sqo, 1sqt |
| Gene: | PLAU (Homo sapiens) |
| Activity: | U-plasminogen activator, with EC number 3.4.21.73 |
| Resources: | FirstGlance, OCA, 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
Several 8-substituted 2-naphthamidine-based inhibitors of the serine protease urokinase plasminogen activator (uPA) are described. Direct attachment of five-membered saturated or unsaturated rings improved inhibitor performance; substitution with sulfones further improved binding profiles. Combination of these substituents or of previously described NH-linked heteroaromatic rings with 6-phenyl amide substituents provided further enhancements to potency and selectivity.
Interaction with the S1 beta-pocket of urokinase: 8-heterocycle substituted and 6,8-disubstituted 2-naphthamidine urokinase inhibitors.,Wendt MD, Geyer A, McClellan WJ, Rockway TW, Weitzberg M, Zhao X, Mantei R, Stewart K, Nienaber V, Klinghofer V, Giranda VL Bioorg Med Chem Lett. 2004 Jun 21;14(12):3063-8. PMID:15149645[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
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
- ↑ Wendt MD, Geyer A, McClellan WJ, Rockway TW, Weitzberg M, Zhao X, Mantei R, Stewart K, Nienaber V, Klinghofer V, Giranda VL. Interaction with the S1 beta-pocket of urokinase: 8-heterocycle substituted and 6,8-disubstituted 2-naphthamidine urokinase inhibitors. Bioorg Med Chem Lett. 2004 Jun 21;14(12):3063-8. PMID:15149645 doi:10.1016/j.bmcl.2004.04.030
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