FIGURE 8.

CDR-H3 of Nb4 adopts a substrate-like binding mode. a, crystal structure of uPA in complex with PAI-1 (PDB code 3PB1) was superimposed to uPA-Nb4. Shown is the reactive loop of the serpin PAI-1 (yellow) and the CDR-H3 of Nb4 (orange). b, crystal structure of trypsin in complex with the standard mechanism inhibitor BPTI (PDB code 4Y0Y) was superimposed to uPA-Nb4. Shown is the reactive loop of BPTI (white) and the CDR-H3 of Nb4 (orange). c, comparison between the CDR-H3's of the anti-matriptase antibody E2 (magenta) (PDB code 3BN9) and Nb4 (orange). The crystal structure of E2 in complex with matriptase was superimposed to uPA-Nb4. In all panels the catalytic Ser-195 colored red, and the residues in uPA (green) that interact with Nb4 are highlighted in light blue. The N and C termini of the peptide segments are indicated in yellow for Nb4, PAI-1, and BPTI and in green for E2.