EC Number   |
Inhibitors |
Structure |
|---|
   7.5.2.6 | (2E)-3-[1-cyclopropyl-7-[(1S)-1-(2,6-dichloro-3-fluorophenyl)ethoxy]naphthalen-2-yl]prop-2-enoic acid |
- |
   |
| 7.5.2.6 | (2E)-3-[6-[(1R)-1-(2,6-dichloro-3-fluorophenyl)ethoxy]quinolin-3-yl]prop-2-enoic acid |
- |
|
| 7.5.2.6 | (2E)-3-[6-[(1S)-1-(2,6-dichloro-3-fluorophenyl)ethoxy]quinolin-3-yl]prop-2-enoic acid |
a quinoline compound with potent activity on purified Escherichia coli MsbA |
|
| 7.5.2.6 | (2E)-3-[6-[(1S)-1-(2,6-dichloro-3-fluorophenyl)ethoxy]quinolin-3-yl]prop-2-enoic acid |
- |
|
| 7.5.2.6 | (2E)-3-[6-[1-(2-chloro-6-cyclopropylphenyl)ethoxy]-4-cyclopropylquinolin-3-yl]prop-2-enoic acid |
selective small-molecule antagonist with bactericidal activity and a dual-mode inhibitory mechanism. (2E)-3-[6-[1-(2-chloro-6-cyclopropylphenyl)ethoxy]-4-cyclopropylquinolin-3-yl]prop-2-enoic acid traps MsbA in an inward-facing, lipopolysaccharide-bound conformation by wedging into an architecturally conserved transmembrane pocket. (2E)-3-[6-[1-(2-chloro-6-cyclopropylphenyl)ethoxy]-4-cyclopropylquinolin-3-yl]prop-2-enoic acid gains access to MsbA through the bulk membrane. The 2-chloro-6 cyclopropylphenyl substituent of (2E)-3-[6-[1-(2-chloro-6-cyclopropylphenyl)ethoxy]-4-cyclopropylquinolin-3-yl]prop-2-enoic acid (A-ring) exhibits strong electron density and makes van der Waals interactions with side chains from transmembrane domains TM4 (L171, A175 and V178), TM5 (A259 and L263) and TM6 (M291 and L294). The quinoline core of (2E)-3-[6-[1-(2-chloro-6-cyclopropylphenyl)ethoxy]-4-cyclopropylquinolin-3-yl]prop-2-enoic acid (B-ring) is orthogonal to the plane of the phenyl substituent, where it is partially enclosed by residues from transmembrane domains TM4 (V178, S179 and I182), TM5 (A259) and TM6 (M295 and L298). A259 and M295 side chains contact the 4-cyclopropyl substitution of the quinoline core and delineate the inhibitor binding-pocket from the inner vestibule of MsbA. (2E)-3-[6-[1-(2-chloro-6-cyclopropylphenyl)ethoxy]-4-cyclopropylquinolin-3-yl]prop-2-enoic acid stabilizes a catalytically incompetent state of the transporter. The inhibitor may have broad relevance across the ABC transporter superfamily |
|
| 7.5.2.6 | (2E)-3-[6-[1-(2-chloro-6-cyclopropylphenyl)ethoxy]-4-cyclopropylquinolin-3-yl]prop-2-enoic acid |
i.e. G907, selective small-molecule antagonist with bactericidal activity and a dual-mode inhibitory mechanism. G907-MsbA binding structure, overview. In the outward-facing StMsbA structure, the G907 pocket is markedly deformed and expected to perturb inhibitor binding. This substantial perturbation of the binding site during the transport cycle defines G907 as an inward-facing state-dependent inhibitor. The inhibitor may have broad relevance across the ABC transporter superfamily |
|
| 7.5.2.6 | AMP-PCP |
- |
|
| 7.5.2.6 | D-20133 |
lipid-based drug, high affinity binding to MsbA |
|
| 7.5.2.6 | ethidium |
antimitotic drug, vinblastine, directly competes with ethidium for binding to MsbA |
|
| 7.5.2.6 | Hoechst 33342 |
complete inhibition of MsbA-mediated Hoechst33342 transport by 0.025 mM taxol, noncompetitive kinetics with Ki of 0.0066 mM, overview |
|
