Fig 9. Crystal Structure of the Protease Domains of FXI and FXIa.

The protease domain of FXIa is shown here superimposed onto the protease domain of the zymogen, FXI. Ile³⁷⁰ (chymotrypsin Ile¹⁶) is shown in magenta for both molecules. For FXI, Arg³⁶⁹ is also shown in gray. Upon activation, the scissile bond between Arg³⁶⁹-Ile³⁷⁰ is cleaved and a new N-terminal sequence (Ile-Val-Gly-Gly) is formed. The new N-terminal Ile³⁷⁰ folds inward toward the catalytic triad and forms a salt bridge with Asp¹⁹⁴. In the FXIa structure, the major conformational change is the positioning of Ile³⁷⁰, a movement of ~20Å from its placement in the zymogen structure. (PDB:2F83 for zymogen and PDB:1ZJD for enzyme were used to create this model using Pymol software (DeLano Scientific LLC, Palo Alto, CA)).