1.B.17.1.1
TolC outer membrane exporter of hemolysin, drugs, siderophores such as enterobactin, etc. (Bleuel et al., 2005). The 3-d structure is available (PDB#1EK9). The three monomers form a continuous channel, and each monomer contributes 4 β-strands to the 12 stranded β-barrel (Koronakis et al. 2000). The Salmonella enterica subspecies Typhi homologue is the ST50 antigen (G4C2H4) used in tests for typhoid fever, and a 2.98 Å resolution structure revealed a trimer that forms an alpha-helical tunnel and a beta-barrel transmembrane channel traversing the periplasmic space and outer membrane, respectively (Guan et al. 2015). K. pneumoniae TolC plays a role in resistance towards most antibiotics, suggesting that it can interact with the AcrB efflux pump (Iyer et al. 2019).  β-lactam drug efflux is mediated by TolC (Kantarcioglu et al. 2024). Molecular dynamics simulations of drug-free TolC reveal essential movements and key residues involved in TolC opening. A whole-gene-saturation mutagenesis assay, mutating each TolC residue and measuring fitness effects under β-lactam selection, was performed, and it was shown the TolC-mediated efflux of three antibiotics: oxacillin, piperacillin, and carbenicillin. Steered molecular dynamics simulations identify general and drug-specific efflux mechanisms, revealing key positions at TolC's periplasmic entry affecting efflux motions (Kantarcioglu et al. 2024).