FIGURE 6.
APA-inhibiting mechanisms of peptidomimetic inhibitors. A, interactions between the inhibitor amastatin and APA. B, interactions between the inhibitor bestatin and APA. Detailed interactions between the inhibitors and APA residues are shown by arrows. Electron density maps of inhibitors correspond to Fo − Fc omit maps (contoured at 2.5σ) that were calculated in the absence of inhibitors. Models of APA-bound inhibitors were built based on these maps. C, detailed interactions between the P1 side chain of amastatin and the S1 pocket of APA. D, detailed interactions between the P1 side chain of bestatin and the S1 pocket of APA. E, detailed interactions between the P3′ side chain of amastatin and the S3′ subsite of APA. F, inhibition of APA catalytic activity by amastatin and bestatin. The catalytic activity of APA on Glu-pNA in the absence of inhibitor was taken as 100%. All values are mean ± S.E. (n = 3).