Prothrombin, conformational

Fondaparinux sodium is the first of a new class of direct-acting antithrombin agents. The anticoagulant activity of heparin depends on the binding of ATIII to a critical pentasaccharide sequence within the heparin molecule. This results in a change in the conformation of AITII. This leads to the inhibitory effect of ATIII on factor Xa, which activates the conversion of prothrombin to thrombin. Fondaparinux is a synthetic pentasaccharide identical to the ATIII-binding site of heparin. 

The conformational change produced in prothrombin on binding of Ca2+ may expose a site that is required for binding to membrane. This may involve the bridging by Ca2+ of gla residues in prothrombin to phosphate groups of the phospholipids.398... 

At the pure air-water interface (Figure 1), the initial rate of adsorption of prothrombin is proportional to the square root of the time, as can be calculated from the curves, indicating that the process, at this interface, is diffusion-controlled, as was observed for native DNA ( ). In the presence of phospholipid monolayers the adsorption process is slower a more complex process must take place at the surface of the membrane, in addition to the conformational change of prothrombin which occurs in the presence of Ca as was found by Nelsestuen (9). It can be the penetration of prothrombin into the lipid layer, as will be described below. 

It was shown in the case of polymers, below surface saturation, that the decrease of capacitance is proportional to their surface concentration (over the whole potential region) (10, 15). It implies that the surface conformation of molecules being adsorbed is established instantaneously and then remains constant. Let us assume that this is also the case for prothrombin. The two maximum surface concentrations F f 2, equivalent to 1.5x10 2 mol.cm , ... 

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