Sites in fibrin involved in the acceleration of plasminogen activation by t-PA. Possible role of fibrin polymerisation.
Polymeric fibrin is a strong enhancer of the activation of plasminogen by t-PA. At least two types of sites are involved in this enhancement i.e. a site within A alpha-(148-160), and a site within gamma-(311-379). These sites are not accessible in fibrinogen, but are exposed upon conversion of fibrinogen to fibrin. This explains why fibrinogen has no rate-enhancing properties, and helps to explain the effects of fibrin. Fibrin with its ordered structure appears to exert its rate-enhancing effect by presenting the above sites for interaction with t-PA and plasminogen; thus concentrating and correctly orienting these two reactants on its surface and inducing conformational changes which lead to higher catalytic efficiencies.
Nieuwenhuizen
W
W
Gaubius Laboratory, TNO-PG, Leiden, The Netherlands.
D000595:Amino Acid Sequence; D001665:Binding Sites; D004789:Enzyme Activation; D005337:Fibrin / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D008969:Molecular Sequence Data; D010958:Plasminogen / Q000378:metabolism*; D011108:Polymers; D013268:Stimulation, Chemical; D010959:Tissue Plasminogen Activator / Q000378:metabolism*
D011108:Polymers; D005337:Fibrin; D010958:Plasminogen; D010959:Tissue Plasminogen Activator