1ycp
THE CRYSTAL STRUCTURE OF FIBRINOGEN-AA PEPTIDE 1-23 (F8Y) BOUND TO BOVINE THROMBIN EXPLAINS WHY THE MUTATION OF PHE-8 TO TYROSINE STRONGLY INHIBITS NORMAL CLEAVAGE AT ARGININE-16THE CRYSTAL STRUCTURE OF FIBRINOGEN-AA PEPTIDE 1-23 (F8Y) BOUND TO BOVINE THROMBIN EXPLAINS WHY THE MUTATION OF PHE-8 TO TYROSINE STRONGLY INHIBITS NORMAL CLEAVAGE AT ARGININE-16
DiseaseDisease
[FIBA_HUMAN] Defects in FGA are a cause of congenital afibrinogenemia (CAFBN) [MIM:202400]. This is a rare autosomal recessive disorder characterized by bleeding that varies from mild to severe and by complete absence or extremely low levels of plasma and platelet fibrinogen. Note=The majority of cases of afibrinogenemia are due to truncating mutations. Variations in position Arg-35 (the site of cleavage of fibrinopeptide a by thrombin) leads to alpha-dysfibrinogenemias. Defects in FGA are a cause of amyloidosis type 8 (AMYL8) [MIM:105200]; also known as systemic non-neuropathic amyloidosis or Ostertag-type amyloidosis. AMYL8 is a hereditary generalized amyloidosis due to deposition of apolipoprotein A1, fibrinogen and lysozyme amyloids. Viscera are particularly affected. There is no involvement of the nervous system. Clinical features include renal amyloidosis resulting in nephrotic syndrome, arterial hypertension, hepatosplenomegaly, cholestasis, petechial skin rash.[1]
FunctionFunction
[THRB_BOVIN] Thrombin, which cleaves bonds after Arg and Lys, converts fibrinogen to fibrin and activates factors V, VII, VIII, XIII, and, in complex with thrombomodulin, protein C. Functions in blood homeostasis, inflammation and wound healing (By similarity). [FIBA_HUMAN] Fibrinogen has a double function: yielding monomers that polymerize into fibrin and acting as a cofactor in platelet aggregation.
About this StructureAbout this Structure
1ycp is a 7 chain structure with sequence from Bos taurus. Full crystallographic information is available from OCA.
See AlsoSee Also
ReferenceReference
- ↑ Malkowski MG, Martin PD, Lord ST, Edwards BF. Crystal structure of fibrinogen-Aalpha peptide 1-23 (F8Y) bound to bovine thrombin explains why the mutation of Phe-8 to tyrosine strongly inhibits normal cleavage at Arg-16. Biochem J. 1997 Sep 15;326 ( Pt 3):815-22. PMID:9307032
- ↑ Bode W. The structure of thrombin: a janus-headed proteinase. Semin Thromb Hemost. 2006 Apr;32 Suppl 1:16-31. PMID:16673263 doi:10.1055/s-2006-939551
- ↑ Benson MD, Liepnieks J, Uemichi T, Wheeler G, Correa R. Hereditary renal amyloidosis associated with a mutant fibrinogen alpha-chain. Nat Genet. 1993 Mar;3(3):252-5. PMID:8097946 doi:http://dx.doi.org/10.1038/ng0393-252