Overall structure of TAFI and comparison with pancreatic carboxypeptidases. (A) Ribbon drawing of TAFI with the activation peptide shown in blue, the catalytic domain in green, and dynamic flap residues 296-350 in orange. The catalytic zinc ion is shown as a magenta sphere and 4 N-linked glycans are shown in yellow stick representation. The cryptic thrombin cleavage site at Arg302 is indicated by an orange sphere. (B,C) TAFI molecule A superimposed on (B) human CPA2 (PDB entry 1AYE; yellow) and (C) human CPB (PDB entry 1KWM; yellow). Superimposition was done using catalytic domain residues only. The rmsd on Cα atoms between TAFI and CPA2 and CPB are 1.1 Å and 0.8 Å, respectively. (D) Radii of the access tunnels to the catalytic site zinc ion were calculated for TAFI (blue), CPA2 (red), and CPB (green).