Sandbox Reserved 689
From Proteopedia
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The AcrB pump is a homotrimer with monomers of 1049 amino acids. The protein has three domains: a transmembrane domain that spans the inner membrane of the bacterium and is responsible for energy transduction, a porter domain which is responsible for selectivity and transport of substrate, and a TolC docking domain that funnels exported substrate into the TolC channel protein. These domains are made up of <scene name='Sandbox_Reserved_689/Secondary_structure/2'>secondary structures</scene>: alpha helices in the TM region and a mixture of alpha helices and beta sheets in the other two domains. There is a lot of "random coil" (shown in blue) inside the porter domain of each monomer. Many of the residues responsible for binding and moving substrate are found in these primary structures. | The AcrB pump is a homotrimer with monomers of 1049 amino acids. The protein has three domains: a transmembrane domain that spans the inner membrane of the bacterium and is responsible for energy transduction, a porter domain which is responsible for selectivity and transport of substrate, and a TolC docking domain that funnels exported substrate into the TolC channel protein. These domains are made up of <scene name='Sandbox_Reserved_689/Secondary_structure/2'>secondary structures</scene>: alpha helices in the TM region and a mixture of alpha helices and beta sheets in the other two domains. There is a lot of "random coil" (shown in blue) inside the porter domain of each monomer. Many of the residues responsible for binding and moving substrate are found in these primary structures. | ||
| - | <scene name='Sandbox_Reserved_689/Monomer_rainbow/1'>N | + | A monomer colored red to blue from <scene name='Sandbox_Reserved_689/Monomer_rainbow/1'>N to C terminus</scene> shows that the three domains are not assembled according to the order of their primary structure. |
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== Substrates == | == Substrates == | ||
Revision as of 13:42, 2 May 2013
| This Sandbox is Reserved from 30/01/2013, through 30/12/2013 for use in the course "Biochemistry II" taught by Hannah Tims at the Messiah College. This reservation includes Sandbox Reserved 686 through Sandbox Reserved 700. |
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Contents |
The E. coli AcrB Efflux Pump
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The is part of a tripartite system used by E. Coli to remove antibiotic and other toxic molecules from the bacterial cell. It works in tandem with , an outer membrane pore can be recruited for many purposes. The beta barrel at the top of the TolC protein spans the outer membrane, allowing the drug to exit the bacterium.
Structural Elements
The AcrB pump is a homotrimer with monomers of 1049 amino acids. The protein has three domains: a transmembrane domain that spans the inner membrane of the bacterium and is responsible for energy transduction, a porter domain which is responsible for selectivity and transport of substrate, and a TolC docking domain that funnels exported substrate into the TolC channel protein. These domains are made up of : alpha helices in the TM region and a mixture of alpha helices and beta sheets in the other two domains. There is a lot of "random coil" (shown in blue) inside the porter domain of each monomer. Many of the residues responsible for binding and moving substrate are found in these primary structures.
A monomer colored red to blue from shows that the three domains are not assembled according to the order of their primary structure.
Substrates
Because of the large binding pockets in AcrB, it is able to bind and export a wide variety of antibiotic drugs and other toxins.
Rifampicin is a high molecular weight drug (~800 g/mol) that has been crystallized in the proximal binding pocket
, interacting residues (all residues within 4 Angstroms) highlighted and shown in ball-and-stick representation.
interacting residues are shown here (Polar in blue, nonpolar in orange).
(switch loop is shown in orange).
(Rifampicin crystal structure from Nakashima, et al. 2011)
Minocycline is a lower molecular weight drug (~400 g/mol) that has been crystallized in the .
(switch loop shown in green)
(blue=polar, green=aliphatic, orange=hydrophobic).
Energy Transduction
There are (Asp408, Asp407, Lys940, and Arg 971) whose protonation and deprotonation are suggested to play a large role in the conformational change between the L, T, and O states (Eicher, et al. 2009). PDB: 3D9B
