View source for 8adi


==Cryo-EM structure of Darobactin 9 bound BAM complex==
<StructureSection load='8adi' size='340' side='right'caption='[[8adi]], [[Resolution|resolution]] 3.40&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[8adi]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli], [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=8ADI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8ADI 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]] 3.4&#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=8adi FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8adi OCA], [https://pdbe.org/8adi PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8adi RCSB], [https://www.ebi.ac.uk/pdbsum/8adi PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8adi ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/BAMD_ECOLI BAMD_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 BamA, the core component of the assembly machinery. Probably involved in transient protein interactions.[HAMAP-Rule:MF_00922]<ref>PMID:16824102</ref> <ref>PMID:20378773</ref> <ref>PMID:21586578</ref> <ref>PMID:21823654</ref> <ref>PMID:22281737</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Over recent decades, the pipeline of antibiotics acting against Gram-negative bacteria is running dry, as most discovered candidate antibiotics suffer from insufficient potency, pharmacokinetic properties, or toxicity. The darobactins, a promising new small peptide class of drug candidates, bind to novel antibiotic target BamA, an outer membrane protein. Previously, we reported that biosynthetic engineering in a heterologous host generated novel darobactins with enhanced antibacterial activity. Here we utilize an optimized purification method and present cryo-EM structures of the Bam complex with darobactin 9 (D9), which served as a blueprint for the biotechnological generation of twenty new darobactins including halogenated analogs. The newly engineered darobactin 22 binds more tightly to BamA and outperforms the favorable activity profile of D9 against clinically relevant pathogens such as carbapenem-resistant Acinetobacter baumannii up to 32-fold, without observing toxic effects.

Darobactins Exhibiting Superior Antibiotic Activity by Cryo-EM Structure Guided Biosynthetic Engineering.,Seyfert CE, Porten C, Yuan B, Deckarm S, Panter F, Bader CD, Coetzee J, Deschner F, Tehrani KHME, Higgins PG, Seifert H, Marlovits TC, Herrmann J, Muller R Angew Chem Int Ed Engl. 2023 Jan 9;62(2):e202214094. doi: 10.1002/anie.202214094. , Epub 2022 Dec 7. PMID:36308277<ref>PMID:36308277</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 8adi" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Escherichia coli]]
[[Category: Escherichia coli K-12]]
[[Category: Large Structures]]
[[Category: Synthetic construct]]
[[Category: Marlovits TC]]
[[Category: Yuan B]]