Importance of factor VIIa Gla-domain residue Arg-36 for recognition of the macromolecular substrate factor X Gla-domain

Macromolecular substrate docking that involves coagulation enzyme-cofactor complexes typically requires multiple contacts distant from an enzyme's catalytic cleft. To illustrate the role of the VIIa Gla-domain in macromolecular substrate docking, a group of site-directed mutants of this domain were generated and characterized. Analysis reveals that specific residues of the VIIa Gla-domain have a critical role in the activation of the macromolecular substrate factor X, one that is dependent on the Gla domain of the substrate being properly folded.