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| | ==Crystal structure of E. coli multidrug transporter MdfA in complex with chloramphenicol== | | ==Crystal structure of E. coli multidrug transporter MdfA in complex with chloramphenicol== |
| - | <StructureSection load='4zow' size='340' side='right' caption='[[4zow]], [[Resolution|resolution]] 2.45Å' scene=''> | + | <StructureSection load='4zow' size='340' side='right'caption='[[4zow]], [[Resolution|resolution]] 2.45Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4zow]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4ZOW OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4ZOW FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4zow]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli_K-12 Escherichia coli K-12]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4ZOW OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4ZOW FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CLM:CHLORAMPHENICOL'>CLM</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.45Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4zp0|4zp0]], [[4zp2|4zp2]]</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CLM:CHLORAMPHENICOL'>CLM</scene></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4zow FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4zow OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4zow RCSB], [http://www.ebi.ac.uk/pdbsum/4zow PDBsum]</span></td></tr> | + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4zow FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4zow OCA], [https://pdbe.org/4zow PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4zow RCSB], [https://www.ebi.ac.uk/pdbsum/4zow PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4zow ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/MDFA_ECOLI MDFA_ECOLI]] Efflux pump driven by the proton motive force. Confers resistance to a broad spectrum of chemically unrelated drugs. Confers resistance to a diverse group of cationic or zwitterionic lipophilic compounds such as ethidium bromide, tetraphenylphosphonium, rhodamine, daunomycin, benzalkonium, rifampicin, tetracycline, puromycin, and to chemically unrelated, clinically important antibiotics such as chloramphenicol, erythromycin, and certain aminoglycosides and fluoroquinolones. Overexpression results in isopropyl-beta-D-thiogalactopyranoside (IPTG) exclusion and spectinomycin sensitivity. Transport of neutral substrates is electrogenic, whereas transport of cationic substrates is electroneutral. In addition to its role in multidrug resistance, confers extreme alkaline pH resistance, allowing the growth under conditions that are close to those used normally by alkaliphiles. This activity requires Na(+) or K(+).<ref>PMID:12578981</ref> <ref>PMID:15371593</ref> <ref>PMID:9079913</ref> <ref>PMID:9644262</ref> <ref>PMID:9811673</ref> | + | [https://www.uniprot.org/uniprot/MDFA_ECOLI MDFA_ECOLI] Efflux pump driven by the proton motive force. Confers resistance to a broad spectrum of chemically unrelated drugs. Confers resistance to a diverse group of cationic or zwitterionic lipophilic compounds such as ethidium bromide, tetraphenylphosphonium, rhodamine, daunomycin, benzalkonium, rifampicin, tetracycline, puromycin, and to chemically unrelated, clinically important antibiotics such as chloramphenicol, erythromycin, and certain aminoglycosides and fluoroquinolones. Overexpression results in isopropyl-beta-D-thiogalactopyranoside (IPTG) exclusion and spectinomycin sensitivity. Transport of neutral substrates is electrogenic, whereas transport of cationic substrates is electroneutral. In addition to its role in multidrug resistance, confers extreme alkaline pH resistance, allowing the growth under conditions that are close to those used normally by alkaliphiles. This activity requires Na(+) or K(+).<ref>PMID:12578981</ref> <ref>PMID:15371593</ref> <ref>PMID:9079913</ref> <ref>PMID:9644262</ref> <ref>PMID:9811673</ref> |
| - | <div style="background-color:#fffaf0;">
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| - | == Publication Abstract from PubMed ==
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| - | Multidrug resistance is a serious threat to public health. Proton motive force-driven antiporters from the major facilitator superfamily (MFS) constitute a major group of multidrug-resistance transporters. Currently, no reports on crystal structures of MFS antiporters in complex with their substrates exist. The E. coli MdfA transporter is a well-studied model system for biochemical analyses of multidrug-resistance MFS antiporters. Here, we report three crystal structures of MdfA-ligand complexes at resolutions up to 2.0 A, all in the inward-facing conformation. The substrate-binding site sits proximal to the conserved acidic residue, D34. Our mutagenesis studies support the structural observations of the substrate-binding mode and the notion that D34 responds to substrate binding by adjusting its protonation status. Taken together, our data unveil the substrate-binding mode of MFS antiporters and suggest a mechanism of transport via this group of transporters.Cell Research advance online publication 4 August 2015; doi:10.1038/cr.2015.94.
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| - | Substrate-bound structure of the E. coli multidrug resistance transporter MdfA.,Heng J, Zhao Y, Liu M, Liu Y, Fan J, Wang X, Zhao Y, Zhang XC Cell Res. 2015 Aug 4. doi: 10.1038/cr.2015.94. PMID:26238402<ref>PMID:26238402</ref>
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| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
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| - | </div>
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| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Heng, J]] | + | [[Category: Escherichia coli K-12]] |
| - | [[Category: Wang, X]] | + | [[Category: Large Structures]] |
| - | [[Category: Zhang, X C]] | + | [[Category: Heng J]] |
| - | [[Category: Zhao, Y]] | + | [[Category: Wang X]] |
| - | [[Category: Cm]] | + | [[Category: Zhang XC]] |
| - | [[Category: Mdfa]] | + | [[Category: Zhao Y]] |
| - | [[Category: Mfs family]]
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| - | [[Category: Multi-drug antiporter]]
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| - | [[Category: Transport protein]]
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| Structural highlights
Function
MDFA_ECOLI Efflux pump driven by the proton motive force. Confers resistance to a broad spectrum of chemically unrelated drugs. Confers resistance to a diverse group of cationic or zwitterionic lipophilic compounds such as ethidium bromide, tetraphenylphosphonium, rhodamine, daunomycin, benzalkonium, rifampicin, tetracycline, puromycin, and to chemically unrelated, clinically important antibiotics such as chloramphenicol, erythromycin, and certain aminoglycosides and fluoroquinolones. Overexpression results in isopropyl-beta-D-thiogalactopyranoside (IPTG) exclusion and spectinomycin sensitivity. Transport of neutral substrates is electrogenic, whereas transport of cationic substrates is electroneutral. In addition to its role in multidrug resistance, confers extreme alkaline pH resistance, allowing the growth under conditions that are close to those used normally by alkaliphiles. This activity requires Na(+) or K(+).[1] [2] [3] [4] [5]
References
- ↑ Lewinson O, Adler J, Poelarends GJ, Mazurkiewicz P, Driessen AJ, Bibi E. The Escherichia coli multidrug transporter MdfA catalyzes both electrogenic and electroneutral transport reactions. Proc Natl Acad Sci U S A. 2003 Feb 18;100(4):1667-72. Epub 2003 Feb 10. PMID:12578981 doi:http://dx.doi.org/10.1073/pnas.0435544100
- ↑ Lewinson O, Padan E, Bibi E. Alkalitolerance: a biological function for a multidrug transporter in pH homeostasis. Proc Natl Acad Sci U S A. 2004 Sep 28;101(39):14073-8. Epub 2004 Sep 15. PMID:15371593 doi:http://dx.doi.org/10.1073/pnas.0405375101
- ↑ Edgar R, Bibi E. MdfA, an Escherichia coli multidrug resistance protein with an extraordinarily broad spectrum of drug recognition. J Bacteriol. 1997 Apr;179(7):2274-80. PMID:9079913
- ↑ Mine T, Morita Y, Kataoka A, Mizushima T, Tsuchiya T. Evidence for chloramphenicol/H+ antiport in Cmr (MdfA) system of Escherichia coli and properties of the antiporter. J Biochem. 1998 Jul;124(1):187-93. PMID:9644262
- ↑ Bohn C, Bouloc P. The Escherichia coli cmlA gene encodes the multidrug efflux pump Cmr/MdfA and is responsible for isopropyl-beta-D-thiogalactopyranoside exclusion and spectinomycin sensitivity. J Bacteriol. 1998 Nov;180(22):6072-5. PMID:9811673
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