| Structural highlights
3ig6 is a 4 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: | 1sqa, 1w14, 1vja, 1owj, 1f92 |
| Gene: | PLAU (HUMAN) |
| 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
In this Letter we report the synthesis and evaluation of a series of non-amidine inhibitors of Urokinase Plasminogen Activator (uPA). Starting from compound 1, a significant change provided compounds in which the amidine, binding in the S1 pocket, was replaced with a primary amine. Further modifications led to the identification of potent, selective, and orally bioavailable uPA inhibitors.
Identification of orally bioavailable, non-amidine inhibitors of Urokinase Plasminogen Activator (uPA).,West CW, Adler M, Arnaiz D, Chen D, Chu K, Gualtieri G, Ho E, Huwe C, Light D, Phillips G, Pulk R, Sukovich D, Whitlow M, Yuan S, Bryant J Bioorg Med Chem Lett. 2009 Oct 1;19(19):5712-5. Epub 2009 Aug 7. PMID:19703768[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
- ↑ West CW, Adler M, Arnaiz D, Chen D, Chu K, Gualtieri G, Ho E, Huwe C, Light D, Phillips G, Pulk R, Sukovich D, Whitlow M, Yuan S, Bryant J. Identification of orally bioavailable, non-amidine inhibitors of Urokinase Plasminogen Activator (uPA). Bioorg Med Chem Lett. 2009 Oct 1;19(19):5712-5. Epub 2009 Aug 7. PMID:19703768 doi:10.1016/j.bmcl.2009.08.008
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