6bpl
From Proteopedia
(Difference between revisions)
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<StructureSection load='6bpl' size='340' side='right' caption='[[6bpl]], [[Resolution|resolution]] 2.91Å' scene=''> | <StructureSection load='6bpl' size='340' side='right' caption='[[6bpl]], [[Resolution|resolution]] 2.91Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>[[6bpl]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6BPL OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6BPL FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6bpl]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Eco57 Eco57]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6BPL OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6BPL FirstGlance]. <br> |
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=3PE:1,2-DIACYL-SN-GLYCERO-3-PHOSPHOETHANOLAMINE'>3PE</scene>, <scene name='pdbligand=AU7:(2E)-3-{6-[(1S)-1-(2-chloro-6-cyclopropylphenyl)ethoxy]-4-cyclopropylquinolin-3-yl}prop-2-enoic+acid'>AU7</scene>, <scene name='pdbligand=DAO:LAURIC+ACID'>DAO</scene>, <scene name='pdbligand=DPO:DIPHOSPHATE'>DPO</scene>, <scene name='pdbligand=FTT:3-HYDROXY-TETRADECANOIC+ACID'>FTT</scene>, <scene name='pdbligand=GCS:D-GLUCOSAMINE'>GCS</scene>, <scene name='pdbligand=GLC:ALPHA-D-GLUCOSE'>GLC</scene>, <scene name='pdbligand=GMH:L-GLYCERO-D-MANNO-HEPTOPYRANOSE'>GMH</scene>, <scene name='pdbligand=KDO:3-DEOXY-D-MANNO-OCT-2-ULOSONIC+ACID'>KDO</scene>, <scene name='pdbligand=MYR:MYRISTIC+ACID'>MYR</scene>, <scene name='pdbligand=PA1:2-AMINO-2-DEOXY-ALPHA-D-GLUCOPYRANOSE'>PA1</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene></td></tr> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=3PE:1,2-DIACYL-SN-GLYCERO-3-PHOSPHOETHANOLAMINE'>3PE</scene>, <scene name='pdbligand=AU7:(2E)-3-{6-[(1S)-1-(2-chloro-6-cyclopropylphenyl)ethoxy]-4-cyclopropylquinolin-3-yl}prop-2-enoic+acid'>AU7</scene>, <scene name='pdbligand=DAO:LAURIC+ACID'>DAO</scene>, <scene name='pdbligand=DPO:DIPHOSPHATE'>DPO</scene>, <scene name='pdbligand=FTT:3-HYDROXY-TETRADECANOIC+ACID'>FTT</scene>, <scene name='pdbligand=GCS:D-GLUCOSAMINE'>GCS</scene>, <scene name='pdbligand=GLC:ALPHA-D-GLUCOSE'>GLC</scene>, <scene name='pdbligand=GMH:L-GLYCERO-D-MANNO-HEPTOPYRANOSE'>GMH</scene>, <scene name='pdbligand=KDO:3-DEOXY-D-MANNO-OCT-2-ULOSONIC+ACID'>KDO</scene>, <scene name='pdbligand=MYR:MYRISTIC+ACID'>MYR</scene>, <scene name='pdbligand=PA1:2-AMINO-2-DEOXY-ALPHA-D-GLUCOPYRANOSE'>PA1</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene></td></tr> | ||
| + | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">msbA, Z1260, ECs0997 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=83334 ECO57])</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=6bpl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6bpl OCA], [http://pdbe.org/6bpl PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6bpl RCSB], [http://www.ebi.ac.uk/pdbsum/6bpl PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6bpl 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=6bpl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6bpl OCA], [http://pdbe.org/6bpl PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6bpl RCSB], [http://www.ebi.ac.uk/pdbsum/6bpl PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6bpl ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Function == | == Function == | ||
[[http://www.uniprot.org/uniprot/MSBA_ECO57 MSBA_ECO57]] Involved in lipid A export and possibly also in glycerophospholipid export and for biogenesis of the outer membrane. Transmembrane domains (TMD) form a pore in the inner membrane and the ATP-binding domain (NBD) is responsible for energy generation. | [[http://www.uniprot.org/uniprot/MSBA_ECO57 MSBA_ECO57]] Involved in lipid A export and possibly also in glycerophospholipid export and for biogenesis of the outer membrane. Transmembrane domains (TMD) form a pore in the inner membrane and the ATP-binding domain (NBD) is responsible for energy generation. | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | The movement of core-lipopolysaccharide across the inner membrane of Gram-negative bacteria is catalysed by an essential ATP-binding cassette transporter, MsbA. Recent structures of MsbA and related transporters have provided insights into the molecular basis of active lipid transport; however, structural information about their pharmacological modulation remains limited. Here we report the 2.9 A resolution structure of MsbA in complex with G907, a selective small-molecule antagonist with bactericidal activity, revealing an unprecedented mechanism of ABC transporter inhibition. G907 traps MsbA in an inward-facing, lipopolysaccharide-bound conformation by wedging into an architecturally conserved transmembrane pocket. A second allosteric mechanism of antagonism occurs through structural and functional uncoupling of the nucleotide-binding domains. This study establishes a framework for the selective modulation of ABC transporters and provides rational avenues for the design of new antibiotics and other therapeutics targeting this protein family. | ||
| + | |||
| + | Structural basis for dual-mode inhibition of the ABC transporter MsbA.,Ho H, Miu A, Alexander MK, Garcia NK, Oh A, Zilberleyb I, Reichelt M, Austin CD, Tam C, Shriver S, Hu H, Labadie SS, Liang J, Wang L, Wang J, Lu Y, Purkey HE, Quinn J, Franke Y, Clark K, Beresini MH, Tan MW, Sellers BD, Maurer T, Koehler MFT, Wecksler AT, Kiefer JR, Verma V, Xu Y, Nishiyama M, Payandeh J, Koth CM Nature. 2018 May 2. pii: 10.1038/s41586-018-0083-5. doi:, 10.1038/s41586-018-0083-5. PMID:29720648<ref>PMID:29720648</ref> | ||
| + | |||
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 6bpl" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
| + | [[Category: Eco57]] | ||
[[Category: Ho, H]] | [[Category: Ho, H]] | ||
[[Category: Koth, C M]] | [[Category: Koth, C M]] | ||
Revision as of 05:57, 16 May 2018
E. coli MsbA in complex with LPS and inhibitor G907
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Categories: Eco57 | Ho, H | Koth, C M | Payandeh, J | Abc transporter | Inhibitor | Lipid transport | Lp | Msba
