3vvs: Difference between revisions
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<StructureSection load='3vvs' size='340' side='right'caption='[[3vvs]], [[Resolution|resolution]] 2.60Å' scene=''> | <StructureSection load='3vvs' size='340' side='right'caption='[[3vvs]], [[Resolution|resolution]] 2.60Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[3vvs]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/ | <table><tr><td colspan='2'>[[3vvs]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Pyrococcus_furiosus Pyrococcus furiosus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3VVS OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3VVS FirstGlance]. <br> | ||
</td></tr><tr id=' | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.6Å</td></tr> | ||
<tr id=' | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACE:ACETYL+GROUP'>ACE</scene>, <scene name='pdbligand=DPN:D-PHENYLALANINE'>DPN</scene>, <scene name='pdbligand=OLC:(2R)-2,3-DIHYDROXYPROPYL+(9Z)-OCTADEC-9-ENOATE'>OLC</scene></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=3vvs FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3vvs OCA], [https://pdbe.org/3vvs PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3vvs RCSB], [https://www.ebi.ac.uk/pdbsum/3vvs PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3vvs ProSAT]</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=3vvs FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3vvs OCA], [https://pdbe.org/3vvs PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3vvs RCSB], [https://www.ebi.ac.uk/pdbsum/3vvs PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3vvs ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Function == | |||
[https://www.uniprot.org/uniprot/Q8U2X0_PYRFU Q8U2X0_PYRFU] | |||
<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
== Publication Abstract from PubMed == | == Publication Abstract from PubMed == | ||
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__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: | [[Category: Pyrococcus furiosus]] | ||
[[Category: | [[Category: Ishitani R]] | ||
[[Category: | [[Category: Nureki O]] | ||
[[Category: | [[Category: Tanaka Y]] | ||
Latest revision as of 15:39, 8 November 2023
Crystal structure of MATE in complex with MaD3SCrystal structure of MATE in complex with MaD3S
Structural highlights
FunctionPublication Abstract from PubMedMultidrug and toxic compound extrusion (MATE) family transporters are conserved in the three primary domains of life (Archaea, Bacteria and Eukarya), and export xenobiotics using an electrochemical gradient of H(+) or Na(+) across the membrane. MATE transporters confer multidrug resistance to bacterial pathogens and cancer cells, thus causing critical reductions in the therapeutic efficacies of antibiotics and anti-cancer drugs, respectively. Therefore, the development of MATE inhibitors has long been awaited in the field of clinical medicine. Here we present the crystal structures of the H(+)-driven MATE transporter from Pyrococcus furiosus in two distinct apo-form conformations, and in complexes with a derivative of the antibacterial drug norfloxacin and three in vitro selected thioether-macrocyclic peptides, at 2.1-3.0 A resolutions. The structures, combined with functional analyses, show that the protonation of Asp 41 on the amino (N)-terminal lobe induces the bending of TM1, which in turn collapses the N-lobe cavity, thereby extruding the substrate drug to the extracellular space. Moreover, the macrocyclic peptides bind the central cleft in distinct manners, which correlate with their inhibitory activities. The strongest inhibitory peptide that occupies the N-lobe cavity may pave the way towards the development of efficient inhibitors against MATE transporters. Structural basis for the drug extrusion mechanism by a MATE multidrug transporter.,Tanaka Y, Hipolito CJ, Maturana AD, Ito K, Kuroda T, Higuchi T, Katoh T, Kato HE, Hattori M, Kumazaki K, Tsukazaki T, Ishitani R, Suga H, Nureki O Nature. 2013 Apr 11;496(7444):247-51. doi: 10.1038/nature12014. Epub 2013 Mar 27. PMID:23535598[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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