Interaction with thrombin

Bourdon P, Jablonski J, Chao BH, Maraganore JM. Structure-function relationships of hirulog peptide interactions with thrombin. FEBS 1991 294 163-166. 

The anticoagulant activity of heparin is endowed by its ability to form strong complexes with a variety of blood clotting factors and thus neutralize their action. For instance, heparin interacts with thrombin, fibrinogen, prothrombin, factors IX-XII... 

Active clotting factors (lla, IXa, Xa, Xla, Xlla, Xllla) a-globulin that inhibits serine proteases, including several of the clotting factors, for example, thrombin (Factor II, Figure 20.5). In the absence of heparin, antithrombin III interacts with thrombin... 

OkumuraT, HasitzM, Jamieson GA. Platdet glyoocalidit Interaction with thrombin and role as thrombin receptor of the platdd surface. J Biol Chem 1978 253 3435-43. 

The cellular interaction of agonists depends on the physico-chemical nature and on the topographical distribution of the membrane receptors (62). Thus thrombin and PGE, mediated responses would depend on the number and the type (high affinity/low affinity) of receptors available for interaction with thrombin or PGE, respectively. The possibility diat platelets fiwrn SHR exhibit greater sensitivity to thrombin and PGE, because of differences in munber or affinity of their respective receptors has been examined by us (23,24). Hirombin as well as PGE, binding sites/platelets and dissociation constants have been found to be similar in WKY and SHR platelets (Fig.7, ref 23,24). Therefore, increased platelet reactivity to thrombin or PGE, is not attributable to changes in the number or the affinity of their respective receptors. 

Antithrombin III is a very slowly hydrolyzed substrate of thrombin. Hence, its interaction with thrombin requires a fully formed active site on the enzyme. 

Wallace A, Dennis S, Hofsteenge J, et al. (1989). Contribution of the N-terminal region of hirudin to its interaction with thrombin. Biochem. 28 10079-10084. 

Based on their specific and reversible interactions with thrombin, PAOM resins have been used as stationary phases for affinity chromatography of the protease (12). Thus, in a simple one-step chromatographic procedure, human thrombin was isolated from activated prothrombin complex concentrate in high purity and yield Because of their excellent mechanical properties the... 

In the present paper, we report high-performance affinity chromatography of thrombin in presence of AT III and Hep, using two types of resins as stationary phases either heparin-like PSSO or AT Ill-like PAOM. In order to differentiate their mechanisms of interaction with thrombin, we examined the chromatographic behavior of thrombin in the presence, or in the absence of AT III and/or heparin. Finally, thrombin was injected on the columns at low ionic strength. The desorption of bound thrombin from the two solid surfaces was then carried out using AT III, heparin and the AT Ill-Hep complex, to elucidate the specificity of the interactions involved. 

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