6gv1: Difference between revisions

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<StructureSection load='6gv1' size='340' side='right' caption='[[6gv1]], [[Resolution|resolution]] 3.40&Aring;' scene=''>
<StructureSection load='6gv1' size='340' side='right' caption='[[6gv1]], [[Resolution|resolution]] 3.40&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[6gv1]] is a 3 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6GV1 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6GV1 FirstGlance]. <br>
<table><tr><td colspan='2'>[[6gv1]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Ecoli Ecoli] and [http://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6GV1 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6GV1 FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=6gv1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6gv1 OCA], [http://pdbe.org/6gv1 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6gv1 RCSB], [http://www.ebi.ac.uk/pdbsum/6gv1 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6gv1 ProSAT]</span></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=6gv1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6gv1 OCA], [http://pdbe.org/6gv1 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6gv1 RCSB], [http://www.ebi.ac.uk/pdbsum/6gv1 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6gv1 ProSAT]</span></td></tr>
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<div style="background-color:#fffaf0;">
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
== Publication Abstract from PubMed ==
The active efflux of antibiotics by multidrug-resistance (MDR) transporters is a major pathway of drug resistance and complicates the clinical treatment of bacterial infections. MdfA is a member of the major facilitator superfamily (MFS) from Escherichia coli and provides resistance to a wide variety of dissimilar toxic compounds, including neutral, cationic and zwitterionic substances. The 12-transmembrane-helix MdfA was expressed as a GFP-octahistidine fusion protein with a TEV protease cleavage site. Following tag removal, MdfA was purified using two chromatographic steps, complexed with a Fab fragment and further purified using size-exclusion chromatography. MdfA and MdfA-Fab complexes were subjected to both vapour-diffusion and lipidic cubic phase (LCP) crystallization techniques. Vapour-diffusion-grown crystals were of type II, with poor diffraction behaviour and weak crystal contacts. LCP lipid screening resulted in type I crystals that diffracted to 3.4 A resolution and belonged to the hexagonal space group P6122.
Multidrug resistance (MDR) poses a major challenge to medicine. A principle cause of MDR is through active efflux by MDR transporters situated in the bacterial membrane. Here we present the crystal structure of the major facilitator superfamily (MFS) drug/H(+) antiporter MdfA from Escherichia coli in an outward open conformation. Comparison with the inward facing (drug binding) state shows that, in addition to the expected change in relative orientations of the N- and C-terminal lobes of the antiporter, the conformation of TM5 is kinked and twisted. In vitro reconstitution experiments demonstrate the importance of selected residues for transport and molecular dynamics simulations are used to gain insights into antiporter switching. With the availability of structures of alternative conformational states, we anticipate that MdfA will serve as a model system for understanding drug efflux in MFS MDR antiporters.


The multidrug-resistance transporter MdfA from Escherichia coli: crystallization and X-ray diffraction analysis.,Nagarathinam K, Jaenecke F, Nakada-Nakura Y, Hotta Y, Liu K, Iwata S, Stubbs MT, Nomura N, Tanabe M Acta Crystallogr F Struct Biol Commun. 2017 Jul 1;73(Pt 7):423-430. doi:, 10.1107/S2053230X17008500. Epub 2017 Jun 20. PMID:28695852<ref>PMID:28695852</ref>
Outward open conformation of a Major Facilitator Superfamily multidrug/H(+) antiporter provides insights into switching mechanism.,Nagarathinam K, Nakada-Nakura Y, Parthier C, Terada T, Juge N, Jaenecke F, Liu K, Hotta Y, Miyaji T, Omote H, Iwata S, Nomura N, Stubbs MT, Tanabe M Nat Commun. 2018 Oct 1;9(1):4005. doi: 10.1038/s41467-018-06306-x. PMID:30275448<ref>PMID:30275448</ref>


From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Ecoli]]
[[Category: Lk3 transgenic mice]]
[[Category: Nagarathinam, K]]
[[Category: Nagarathinam, K]]
[[Category: Parthier, C]]
[[Category: Parthier, C]]
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