Hyperactivity of factor IX Padua (R338L) depends on factor VIIIa cofactor activity. [PDF]
JCI Insight, 2019 Adeno-associated-viral (AAV) vector liver-directed gene therapy (GT) for hemophilia B (HB) is limited by a vector-dose-dependent hepatotoxicity. Recently, this obstacle has been partially circumvented by the use of a hyperactive factor IX (FIX) variant ...
Samelson-Jones BJ +4 more
europepmc +6 more sources
Factor VIIIa A2 subunit shows a high affinity interaction with factor IXa: contribution of A2 subunit residues 707-714 to the interaction with factor IXa. [PDF]
J Biol Chem, 2013 Background: FVIIIa binds FIXa through interactions involving A2 and A3C1C2 subunits. Results: A2 subunit shows a high affinity interaction for FIXa with contribution of residues 707-714 to this interaction.
Griffiths AE, Rydkin I, Fay PJ.
europepmc +6 more sources
Membrane Interaction of the Factor VIIIa Discoidin Domains in Atomistic Detail. [PDF]
Biochemistry, 2015 A recently developed membrane-mimetic model was applied to study membrane interaction and binding of the two anchoring C2-like discoidin domains of human coagulation factor VIIIa (FVIIIa), the C1 and C2 domains. Both individual domains, FVIII C1 and FVIII C2, were observed to bind the phospholipid membrane by partial or full insertion of their ...
Madsen JJ +5 more
europepmc +6 more sources
Identification of residues contributing to A2 domain-dependent structural stability in factor VIII and factor VIIIa. [PDF]
J Biol Chem, 2008 Factor VIII circulates as a heterodimer composed of heavy (A1A2B domains) and light (A3C1C2 domains) chains, whereas the contiguous A1A2 domains are separate subunits in the active cofactor, factor VIIIa.
Wakabayashi H, Fay PJ.
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Cofactor activity in factor VIIIa of the blood clotting pathway is stabilized by an interdomain bond between His281 and Ser524 formed in factor VIII. [PDF]
J Biol Chem, 2014 Background: Intermediate resolution FVIII x-ray structures show His281 (A1) and Ser524 (A2) in close proximity. Ala mutations at these residues show functional defects.
Wakabayashi H, Monaghan M, Fay PJ.
europepmc +3 more sources
Stabilizing interactions between D666-S1787 and T657-Y1792 at the A2-A3 interface support factor VIIIa stability in the blood clotting pathway. [PDF]
J Thromb Haemost, 2016 Monaghan M +3 more
europepmc +4 more sources
Mim8, a novel factor VIIIa mimetic bispecific antibody, shows favorable safety and pharmacokinetics in healthy adults. [PDF]
Res Pract Thromb Haemost, 2023 Persson P +4 more
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Enhanced factor VIIIa stability of A2 domain interface variants results from an increased apparent affinity for the A2 subunit. Results from an increased apparent affinity for the A2 subunit. [PDF]
Thromb Haemost, 2014 Monaghan M +4 more
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Role of hydrophobic mutations on the binding affinity and stability of blood coagulation factor VIIIa: a computational molecular dynamics and free-energy analysis. [PDF]
Biochem Biophys Res Commun, 2014 Venkateswarlu D.
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Blood, 2021 Østergaard and colleagues report the development of a potent bispecific antibody, Mim8, which binds both activated factor IX and factor X, mimicking the propagation of coagulation by activated factor VIII.
Østergaard H +31 more
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