Article
Effects of replacement of factor VIII amino acids Asp519 and Glu665 with Val on plasma survival and efficacy in vivo.
The AAPS journal - 1 Sept 2014
Kosloski Matthew P, Shetty Krithika A, Wakabayashi Hironao, Fay Philip J, Balu-Iyer Sathy V
Abstract excerpt
Proteolytic cleavage of factor VIII (FVIII) to activated FVIIIa is required for participation in the coagulation cascade. The A2 domain is no longer covalently bound in the resulting activated heterotrimer and is highly unstable. Aspartic acid (D) 519 and glutamic acid (E) 665 at the A1-A2 and A2-A3 domain interfaces were identified as acidic residues in local hydrophobic pockets. Replacement with hydrophobic...
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