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| {{STRUCTURE_2hqg| PDB=2hqg | SCENE= }} | | {{STRUCTURE_2hqg| PDB=2hqg | SCENE= }} |
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| '''Conformation of the AcrB Multidrug Efflux Pump in Mutants of the Putative Proton Relay Pathway'''
| | ===Conformation of the AcrB Multidrug Efflux Pump in Mutants of the Putative Proton Relay Pathway=== |
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| ==Overview==
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| We previously reported the X-ray structures of wild-type Escherichia coli AcrB, a proton motive force-dependent multidrug efflux pump, and its N109A mutant. These structures presumably reflect the resting state of AcrB, which can bind drugs. After ligand binding, a proton may bind to an acidic residue(s) in the transmembrane domain, i.e., Asp407 or Asp408, within the putative network of electrostatically interacting residues, which also include Lys940 and Thr978, and this may initiate a series of conformational changes that result in drug expulsion. Herein we report the X-ray structures of four AcrB mutants, the D407A, D408A, K940A, and T978A mutants, in which the structure of this tight electrostatic network is expected to become disrupted. These mutant proteins revealed remarkably similar conformations, which show striking differences from the previously known conformations of the wild-type protein. For example, the loop containing Phe386 and Phe388, which play a major role in the initial binding of substrates in the central cavity, becomes prominently extended into the center of the cavity, such that binding of large substrate molecules may become difficult. We believe that this new conformation may mimic, at least partially, one of the transient conformations of the transporter during the transport cycle.
| | The line below this paragraph, {{ABSTRACT_PUBMED_17015668}}, adds the Publication Abstract to the page |
| | (as it appears on PubMed at http://www.pubmed.gov), where 17015668 is the PubMed ID number. |
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| | {{ABSTRACT_PUBMED_17015668}} |
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| ==About this Structure== | | ==About this Structure== |
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| [[Category: Membrane protein]] | | [[Category: Membrane protein]] |
| [[Category: Multidrug efflux pump]] | | [[Category: Multidrug efflux pump]] |
| ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May 4 06:35:03 2008'' | | |
| | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jul 29 03:50:45 2008'' |