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- W2591560795 abstract "Abstract Abstract 4421 Factor VIIa (fVIIa) is one of the key proteins in the blood coagulation cascade. It activates factors IX and × on a negatively charged phospholipid surface in either a TF-dependent or TF-independent fashion (Silverberg et al, 1977; Bom et al, 1990). Monroe et al (1997) demonstrated that fVIIa binds to activated platelets independent of TF and partially restores thrombin generation in an in vitro model of hemophilia. Thus, it appears that interaction of fVIIa with platelet phospholipids plays an important role. We report that binding of 1,2-dihexanoyl-sn-glycero-3-phospholipids -L-serine (C6PS) and 1,2-dihexanoyl-sn-glycero-3-phosphoethanolamine (C6PE) to fVIIa causes changes in its activity as well as structure. Titration with C6PS led to changes in intrinsic fluorescence indicative of two or more binding sites for this lipid. Similar titrations with C6PE indicated that it probably binds to a single site on the protein. Experiments are underway to test this initial conclusion. Both lipids bind with comparable affinity (kd ~ 165 and 160 μ M) when data were analyzed using a single site model. We also examined the effect of the soluble lipids on the activity of fVIIa. Both C6PS and C6PE binding increased fVIIa proteolytic and amidolytic activity, with the effect of C6PS being more pronounced. Based on current data, it appears that both lipids bind to a single weak site, but that binding of either to this site promotes binding of C6PS to a second, tighter, and C6PS-specific site, which seems to be crucial in regulating activity. Further experiments are underway to test this hypothesis. Disclosures: No relevant conflicts of interest to declare." @default.
- W2591560795 created "2017-03-03" @default.
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- W2591560795 date "2010-11-19" @default.
- W2591560795 modified "2023-09-28" @default.
- W2591560795 title "The Interaction of Soluble Phospholipids with Coagulation Factor VIIa" @default.
- W2591560795 doi "https://doi.org/10.1182/blood.v116.21.4421.4421" @default.
- W2591560795 hasPublicationYear "2010" @default.
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