Proteinase inhibitors molecular differences

Like the serpins, AMG is a proteinase inhibitor. It is unlike the serpins in many aspects, however. First, it is a very large molecule, with a molecular mass of -725 kDa. As a result, only very small amounts diffuse out of the plasma space. Second, it acts as a substrate for proteases but does not block their active sites instead, it enfolds the still-active proteases to block access of proteins but not small substrates. Third, it inhibits many different classes of proteinases, mcluding those with serine, cysteine, and metal ions in their proteolytic sites. Fourth, it is structurally related to pregnancy zone protein and to the complement components C3, C4, and C5 rather than to the serpins. Like these proteins, it contains an intrachain thiol ester bond that is necessary for activity and the breaking of which results in a conformational change of the peptide chain. 

Another inhibitor is present in plasma that can inactivate thrombin, plasmin, and, to a much lesser extent, the other proteinases as well. This inhibitor, a2-macroglobulin, inhibits by a completely different mechanism from that of the SERPINS. It entraps the proteinases in a cavity that is created by the four subunits of the ai-macroglobulin molecule. The active sites of the entrapped proteinases are sterically hindered from protein substrates but are accessible to low-molecular-weight chromogenic substrates that are used in some laboratory coagulation tests for heparin and antithrombin. 

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