PubMed:10346902 JSONTXT

{"project":"FSU-PRGE","denotations":[{"id":"T1","span":{"begin":24,"end":43},"obj":"protein"},{"id":"T2","span":{"begin":111,"end":130},"obj":"protein"},{"id":"T3","span":{"begin":229,"end":231},"obj":"protein"},{"id":"T4","span":{"begin":236,"end":238},"obj":"protein"},{"id":"T5","span":{"begin":733,"end":735},"obj":"protein"},{"id":"T6","span":{"begin":741,"end":743},"obj":"protein"},{"id":"T7","span":{"begin":752,"end":754},"obj":"protein"},{"id":"T8","span":{"begin":786,"end":788},"obj":"protein"},{"id":"T9","span":{"begin":996,"end":998},"obj":"protein"},{"id":"T10","span":{"begin":1051,"end":1053},"obj":"protein"},{"id":"T11","span":{"begin":1328,"end":1330},"obj":"protein"},{"id":"T12","span":{"begin":1349,"end":1351},"obj":"protein"}],"text":"Association of terminal complement proteins in solution and modulation by suramin.\nThe association of terminal complement proteins was investigated by analytical ultracentrifugation and multi-angle laser light scattering. Native C8 and C9 formed a heterodimer in solution of physiological ionic strength with a free-energy change DeltaG degrees of -8.3 kcal/mol and a dissociation constant Kd of 0.6 microM (at 20 degrees C) that was ionic strength- and temperature-dependent. A van't Hoff plot of the change in Kd was linear between 10 and 37 degrees C and yielded values of DeltaH degrees = -12.9 kcal/mol and DeltaS degrees = -15.9 cal mol-1 deg-1, suggesting that electrostatic forces play a prominent role in the interaction of C8 with C9. Native C8 also formed a heterodimer with C5, and low concentrations of polyionic ligands such as protamine and suramin inhibited the interaction. Suramin induced high-affinity trimerization of C8 (Kd = 0.10 microM at 20 degrees C) and dimerization of C9 (Kd = 0.86 microM at 20 degrees C). Suramin-induced C8 oligomerization may be the primary reason for the drug's ability to prevent complement-mediated hemolysis. Analysis of sedimentation equilibria and also of the fluorescence enhancement of suramin when bound to protein provided evidence for two suramin-binding sites on each C9 and three on each C8 in the oligomers. Oligomerization could be reversed by high suramin concentrations, but 8-aminonaphthalene-1,3,6- trisulfonate (ANTS2- ), which mimics half a suramin molecule, could not compete with suramin binding and oligomerization suggesting that the drug also binds nonionically to the proteins."}

{"project":"AIMed","denotations":[{"id":"T1","span":{"begin":229,"end":231},"obj":"protein"},{"id":"T2","span":{"begin":236,"end":238},"obj":"protein"},{"id":"T3","span":{"begin":733,"end":735},"obj":"protein"},{"id":"T4","span":{"begin":741,"end":743},"obj":"protein"},{"id":"T5","span":{"begin":752,"end":754},"obj":"protein"},{"id":"T6","span":{"begin":786,"end":788},"obj":"protein"},{"id":"T7","span":{"begin":938,"end":940},"obj":"protein"},{"id":"T8","span":{"begin":996,"end":998},"obj":"protein"},{"id":"T9","span":{"begin":1051,"end":1053},"obj":"protein"},{"id":"T10","span":{"begin":1328,"end":1330},"obj":"protein"},{"id":"T11","span":{"begin":1349,"end":1351},"obj":"protein"}],"text":"Association of terminal complement proteins in solution and modulation by suramin.\nThe association of terminal complement proteins was investigated by analytical ultracentrifugation and multi-angle laser light scattering. Native C8 and C9 formed a heterodimer in solution of physiological ionic strength with a free-energy change DeltaG degrees of -8.3 kcal/mol and a dissociation constant Kd of 0.6 microM (at 20 degrees C) that was ionic strength- and temperature-dependent. A van't Hoff plot of the change in Kd was linear between 10 and 37 degrees C and yielded values of DeltaH degrees = -12.9 kcal/mol and DeltaS degrees = -15.9 cal mol-1 deg-1, suggesting that electrostatic forces play a prominent role in the interaction of C8 with C9. Native C8 also formed a heterodimer with C5, and low concentrations of polyionic ligands such as protamine and suramin inhibited the interaction. Suramin induced high-affinity trimerization of C8 (Kd = 0.10 microM at 20 degrees C) and dimerization of C9 (Kd = 0.86 microM at 20 degrees C). Suramin-induced C8 oligomerization may be the primary reason for the drug's ability to prevent complement-mediated hemolysis. Analysis of sedimentation equilibria and also of the fluorescence enhancement of suramin when bound to protein provided evidence for two suramin-binding sites on each C9 and three on each C8 in the oligomers. Oligomerization could be reversed by high suramin concentrations, but 8-aminonaphthalene-1,3,6- trisulfonate (ANTS2- ), which mimics half a suramin molecule, could not compete with suramin binding and oligomerization suggesting that the drug also binds nonionically to the proteins."}