View source for 7nri


==Structure of the darobactin-bound E. coli BAM complex (BamABCDE)==
<StructureSection load='7nri' size='340' side='right'caption='[[7nri]], [[Resolution|resolution]] 3.03&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7nri]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli_K-12 Escherichia coli K-12] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7NRI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7NRI FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 3.03&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=UX8:(2~{S},3~{R})-2-azanyl-3-(1~{H}-indol-3-yl)-3-oxidanyl-propanoic+acid'>UX8</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=7nri FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7nri OCA], [https://pdbe.org/7nri PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7nri RCSB], [https://www.ebi.ac.uk/pdbsum/7nri PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7nri ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/BAMA_ECOLI BAMA_ECOLI] Part of the outer membrane protein assembly complex, which is involved in assembly and insertion of beta-barrel proteins into the outer membrane. Constitutes, with BamD, the core component of the assembly machinery.<ref>PMID:15951436</ref> <ref>PMID:16102012</ref> <ref>PMID:16824102</ref> <ref>PMID:20378773</ref> <ref>PMID:21823654</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Antibiotics that target Gram-negative bacteria in new ways are needed to resolve the antimicrobial resistance crisis(1-3). Gram-negative bacteria are protected by an additional outer membrane, rendering proteins on the cell surface attractive drug targets(4,5). The natural compound darobactin targets the bacterial insertase BamA(6)-the central unit of the essential BAM complex, which facilitates the folding and insertion of outer membrane proteins(7-13). BamA lacks a typical catalytic centre, and it is not obvious how a small molecule such as darobactin might inhibit its function. Here we resolve the mode of action of darobactin at the atomic level using a combination of cryo-electron microscopy, X-ray crystallography, native mass spectrometry, in vivo experiments and molecular dynamics simulations. Two cyclizations pre-organize the darobactin peptide in a rigid beta-strand conformation. This creates a mimic of the recognition signal of native substrates with a superior ability to bind to the lateral gate of BamA. Upon binding, darobactin replaces a lipid molecule from the lateral gate to use the membrane environment as an extended binding pocket. Because the interaction between darobactin and BamA is largely mediated by backbone contacts, it is particularly robust against potential resistance mutations. Our results identify the lateral gate as a functional hotspot in BamA and will allow the rational design of antibiotics that target this bacterial Achilles heel.

The antibiotic darobactin mimics a beta-strand to inhibit outer membrane insertase.,Kaur H, Jakob RP, Marzinek JK, Green R, Imai Y, Bolla JR, Agustoni E, Robinson CV, Bond PJ, Lewis K, Maier T, Hiller S Nature. 2021 May;593(7857):125-129. doi: 10.1038/s41586-021-03455-w. Epub 2021 , Apr 14. PMID:33854236<ref>PMID:33854236</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 7nri" style="background-color:#fffaf0;"></div>

==See Also==
*[[Bam complex 3D structures|Bam complex 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Escherichia coli K-12]]
[[Category: Large Structures]]
[[Category: Synthetic construct]]
[[Category: Bolla J]]
[[Category: Bond PJ]]
[[Category: Green R]]
[[Category: Hiller S]]
[[Category: Imai Y]]
[[Category: Jakob RP]]
[[Category: Kaur H]]
[[Category: Lewis K]]
[[Category: Maier T]]
[[Category: Marzinek JK]]
[[Category: Robinson C]]