Fig. 6: Deep transmembrane domain-binding pocket (TMD-BP) and a model for allosteric drug binding and transport.
From: Allosteric drug transport mechanism of multidrug transporter AcrB
a Conformational changes of TM11/TM12 in the transmembrane domain of the T protomer induced by drug binding (yellow, unliganded T; cyan, partially induced T in presence of β-lactams; green, partially induced T of 3-FOR bound Gly619Pro; magenta, fully induced T in presence of fusidic acid (FUA) bound to the TMD-BP. b FUA (carbon, black; oxygen, red) binding to TMD-BP of the T protomer (yellow). Inset: Polder electron density map assigned to FUA is contoured at 4.5 σ. c Substrate protection experiment of AcrB-cl_Cys981 and AcrB-cl_Cys875 (negative control) by in-gel fluorescence of MTS-rhodamine modified proteins in dependence of the drug concentration (from left to right increasing concentration of drugs). Data are presented as mean ± s.e.m. of N ≥ 4 independent experiments. The calculated apparent Kiapp for fusidic acid, oxacillin, or novobiocin is 38, 446, or 95 μM, respectively (Source Data Fig. 6c).
