Fig. 9
Model for FK506-binding protein (FKBP)-mediated rotation around the peptidyl-prolyl bond. a S2-W23A peptide bound to full-length TtSlyD (TtSlyDFL) molecule D (β-turn type VIb-like binding mode). The color scheme is the same as for Fig. 5, except that the colors are more subdued. The hypothesized rotations of the P29S2 proline residue are indicated. We suggest that the residue found immediately N-terminal to the peptidyl-prolyl bond are kept anchored during catalysis through β-strand type hydrogen bonds and side chain interactions with the hydrophobic pocket (see also Fig. 5c, d and Fig. 6a). The C-terminal part, including the side chain of the proline, then rotates from the trans to the cis form via the twisted transition state (syn form) or vice versa, as indicated. Notably, the model predicts that the proline side chain penetrates deepest into the pocket in the twisted transition state, which may confer preferential stabilization of this form over the ground states. b Binding of FK506 to TtSlyDFL. The orientation and color scheme are the same as in panel a. The pipecolinyl ring is in the same position as expected for the proline side chain when in the syn form, which supports the notion that FK506 can be viewed as a mimic of the twisted transition state