Crystal structure of urokinase-type plasminogen activator (uPA) complexed with bicyclic peptide UK603 (bicyclic 2)Crystal structure of urokinase-type plasminogen activator (uPA) complexed with bicyclic peptide UK603 (bicyclic 2)

Structural highlights

4os5 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, 4os6, 4os7
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.

References

  1. 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

4os5, resolution 2.26Å

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