1owh

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Template:STRUCTURE 1owh

Substituted 2-Naphthamidine Inhibitors of UrokinaseSubstituted 2-Naphthamidine Inhibitors of Urokinase

Template:ABSTRACT PUBMED 14711304

DiseaseDisease

[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]

FunctionFunction

[UROK_HUMAN] Specifically cleaves the zymogen plasminogen to form the active enzyme plasmin.

About this StructureAbout this Structure

1owh is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA.

See AlsoSee Also

ReferenceReference

[xtra 1]

  1. Wendt MD, Rockway TW, Geyer A, McClellan W, Weitzberg M, Zhao X, Mantei R, Nienaber VL, Stewart K, Klinghofer V, Giranda VL. Identification of novel binding interactions in the development of potent, selective 2-naphthamidine inhibitors of urokinase. Synthesis, structural analysis, and SAR of N-phenyl amide 6-substitution. J Med Chem. 2004 Jan 15;47(2):303-24. PMID:14711304 doi:10.1021/jm0300072
  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

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