6r72

From Proteopedia

(Difference between revisions)

Current revision

Crystal structure of BmrA-E504A in an outward-facing conformation

Structural highlights

6r72 is a 4 chain structure with sequence from Bacillus subtilis. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 3.95Å
Ligands:	,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

BMRA_BACSU An efflux transporter able to transport Hoechst 33342, ethidium bromide, doxorubicin and a number of other drugs in vitro into inside out vesicles. The endogenous substrate is unknown. It has been suggested that NBD dimerization induced by ATP-binding causes a large conformational change responsible for substrate translocation (PubMed:18215075). Transmembrane domains (TMD) form a pore in the inner membrane and the ATP-binding domain (NBD) is responsible for energy generation (Probable).^[1]

Publication Abstract from PubMed

Multidrug ABC transporters translocate drugs across membranes by a mechanism for which the molecular features of drug release are so far unknown. Here, we resolved three ATP-Mg(2+)-bound outward-facing conformations of the Bacillus subtilis (homodimeric) BmrA by x-ray crystallography and single-particle cryo-electron microscopy (EM) in detergent solution, one of them with rhodamine 6G (R6G), a substrate exported by BmrA when overexpressed in B. subtilis. Two R6G molecules bind to the drug-binding cavity at the level of the outer leaflet, between transmembrane (TM) helices 1-2 of one monomer and TM5'-6' of the other. They induce a rearrangement of TM1-2, highlighting a local flexibility that we confirmed by hydrogen/deuterium exchange and molecular dynamics simulations. In the absence of R6G, simulations show a fast postrelease occlusion of the cavity driven by hydrophobicity, while when present, R6G can move within the cavity, maintaining it open.

Substrate-bound and substrate-free outward-facing structures of a multidrug ABC exporter.,Chaptal V, Zampieri V, Wiseman B, Orelle C, Martin J, Nguyen KA, Gobet A, Di Cesare M, Magnard S, Javed W, Eid J, Kilburg A, Peuchmaur M, Marcoux J, Monticelli L, Hogbom M, Schoehn G, Jault JM, Boumendjel A, Falson P Sci Adv. 2022 Jan 28;8(4):eabg9215. doi: 10.1126/sciadv.abg9215. Epub 2022 Jan, 26. PMID:35080979^[2]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Orelle C, Gubellini F, Durand A, Marco S, Levy D, Gros P, Di Pietro A, Jault JM. Conformational change induced by ATP binding in the multidrug ATP-binding cassette transporter BmrA. Biochemistry. 2008 Feb 26;47(8):2404-12. doi: 10.1021/bi702303s. Epub 2008 Jan, 24. PMID:18215075 doi:http://dx.doi.org/10.1021/bi702303s
↑ Chaptal V, Zampieri V, Wiseman B, Orelle C, Martin J, Nguyen KA, Gobet A, Di Cesare M, Magnard S, Javed W, Eid J, Kilburg A, Peuchmaur M, Marcoux J, Monticelli L, Hogbom M, Schoehn G, Jault JM, Boumendjel A, Falson P. Substrate-bound and substrate-free outward-facing structures of a multidrug ABC exporter. Sci Adv. 2022 Jan 28;8(4):eabg9215. doi: 10.1126/sciadv.abg9215. Epub 2022 Jan, 26. PMID:35080979 doi:http://dx.doi.org/10.1126/sciadv.abg9215

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/6r72"

@@ Line 3: / Line 3: @@
 <StructureSection load='6r72' size='340' side='right'caption='[[6r72]], [[Resolution|resolution]] 3.95&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[6r72]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/"vibrio_subtilis"_ehrenberg_1835 "vibrio subtilis" ehrenberg 1835]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6R72 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6R72 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[6r72]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Bacillus_subtilis Bacillus subtilis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6R72 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6R72 FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ATP:ADENOSINE-5-TRIPHOSPHATE'>ATP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</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]] 3.95&#8491;</td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">B4417_3307 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1423 "Vibrio subtilis" Ehrenberg 1835])</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ATP:ADENOSINE-5-TRIPHOSPHATE'>ATP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</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=6r72 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6r72 OCA], [https://pdbe.org/6r72 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6r72 RCSB], [https://www.ebi.ac.uk/pdbsum/6r72 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6r72 ProSAT]</span></td></tr>
 </table>
+== Function ==
+[https://www.uniprot.org/uniprot/BMRA_BACSU BMRA_BACSU] An efflux transporter able to transport Hoechst 33342, ethidium bromide, doxorubicin and a number of other drugs in vitro into inside out vesicles. The endogenous substrate is unknown. It has been suggested that NBD dimerization induced by ATP-binding causes a large conformational change responsible for substrate translocation (PubMed:18215075). Transmembrane domains (TMD) form a pore in the inner membrane and the ATP-binding domain (NBD) is responsible for energy generation (Probable).<ref>PMID:18215075</ref>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 21: / Line 23: @@
 __TOC__
 </StructureSection>
-[[Category: Vibrio subtilis ehrenberg 1835]]
+[[Category: Bacillus subtilis]]
 [[Category: Large Structures]]
-[[Category: Chaptal, V]]
+[[Category: Chaptal V]]
-[[Category: Falson, P]]
+[[Category: Falson P]]
-[[Category: Kilburg, A]]
+[[Category: Kilburg A]]
-[[Category: Magnard, S]]
+[[Category: Magnard S]]
-[[Category: Zampieri, V]]
+[[Category: Zampieri V]]
-[[Category: Abc transporter bmra multi-drug transporter]]
-[[Category: Transport protein]]

6r72

From Proteopedia

Current revision

Crystal structure of BmrA-E504A in an outward-facing conformation

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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