Analysis of highly conserved residue Glu149 in Protein C. (A) Conservation of the C-terminal light chain residues among various protein C species. Forward slash indicates the furin-like cleavage site for posttranslational processing of single-chain protein C into 2 chain; backward slash indicates the activation cleavage site to generate APC. Numbering is for human protein C. (B) The residue corresponding to Glu149 in protein C is conserved in all vitamin K-dependent coagulation factors, with the exception of factor IX. Numbering is for human protein C. (C) Molecular model of APC based on the crystal structure of the protease domain. The C terminus of the protein C light chain was not defined in the x-ray crystallographic structure beyond residue Lys146; hence, the green circle indicates the approximate location of Glu149. Other key residues indicated are the active site catalytic triad in red, 5A-APC substituted residues (Arg229 and Arg230 in the Ca²⁺ binding loop and Lys191, Lys192, and Lys193 in loop 37) in blue, and Glu330 and Glu333, which are apparently required for PAR-1 cleavage by APC, in orange.²⁹  (D) Location of factor Xa residue Glu138 (green), corresponding to protein C Glu149, in a factor Xa model based on its crystallographic structure. The catalytic triad is indicated in red.