C H A P T E R 3 6 , F IG U R E 15
Anticoagulant subsystem. Activation of protein C occurs adjacent to the injury site;
inactivation occurs on the exposed surface at the injury site. Protein C is activated through cleavage by thrombin at
Arg169-Ile170. Protein S is a 635-residue vitamin K-dependent protein that functions as a cofactor. There is a Gla
domain and four EGF-like domains in the molecule, but no proteinase domain. Thrombomodulin is a 554-residue
integral membrane protein. The extracellular region comprises residues 1-494, the transmembrane region residues
495-518, and the intracellular region residues 519-554. EGF-like structures are found from residue 224 to 459.
Motifs and domains are color coded as follows: Gla domain (blue), EGF-like domain (magenta), activation peptide
(yellow), and proteinase domain (green). Light chains are indicated in dark gray, heavy chains in light gray. Regions
connecting the motifs are black.
A T m ( C le a v e d )
I n a c tiv e
S e r p in
C H A P T E R 3 6 , F IG U R E 16
Proteinase inactivation by SERPINS. Proteinase inactivation occurs by reaction
between proteinase and inhibitor, e.g., antithrombin. The proteinase is a stoichiometric reactant in this instance but is
not a catalyst. This reaction results in the formation of a covalent bond between the reactive site residue of the
inhibitor (Arg393 in antithrombin) and the active site residue (Ser195 in the proteinase). This complex formation pre-
vents the proteinase from hydrolyzing any other peptide bond. Proteinases, thrombin, factor Xa, factor IXa, and, less
effectively, factor Vila and factor XIa are all inactivated by the plasma protein inhibitor antithrombin (previously des-
ignated antithrombin III). The product ATm is the cleaved form of antithrombin. It is formed in both the absence and
presence of heparin, but more so in the presence. The proteinase is indicated is indicated by green, the inhibitor by
red, and the inactivated proteinase by gray. Stripes on the inhibitor represent the helices (Figure 36-7).
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