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. 2022 Dec 19;66(1):149–169. doi: 10.1021/acs.jmedchem.2c01658

Figure 4.

Figure 4

Rapamycin analogs 11 (PDB 8ER6) and 12 (PDB 8ER7) bind at FKBP12’s canonical rapamycin binding site. (A) Hydroxy analog 11 (darker orange) binds in the FKBP12 (red) pocket partially defined by residue F47. C32 hydroxyl residue donates an intramolecular hydrogen bond with the adjacent ester oxygen (dashed line). (B) Methyl ether 12 (lighter orange) is not able to form this intramolecular hydrogen bond, and the methyl group is oriented toward FKBP12 residue F47. As a result, F47 must shift upward to accommodate this additional steric bulk.