OCA at 12:38, 1 February 2024

OCA — Thu, 01 Feb 2024 12:38:40 GMT

←Older revision		Revision as of 12:38, 1 February 2024
Line 1:		Line 1:

-	====	+	==Crystal structure of E.coli BamA beta-barrel in complex with darobactin (crystal form 2)==
-	<StructureSection load='7nrf' size='340' side='right'caption='[[7nrf]]' scene=''>	+	<StructureSection load='7nrf' size='340' side='right'caption='[[7nrf]], [[Resolution\|resolution]] 2.20Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id= OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol= FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[7nrf]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli_O157:H7 Escherichia coli O157:H7] 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=7NRF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7NRF FirstGlance]. <br>
-	</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=7nrf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7nrf OCA], [https://pdbe.org/7nrf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7nrf RCSB], [https://www.ebi.ac.uk/pdbsum/7nrf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7nrf ProSAT]</span></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]] 2.2Å</td></tr>
		+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=C8E:(HYDROXYETHYLOXY)TRI(ETHYLOXY)OCTANE'>C8E</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <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=7nrf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7nrf OCA], [https://pdbe.org/7nrf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7nrf RCSB], [https://www.ebi.ac.uk/pdbsum/7nrf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7nrf ProSAT]</span></td></tr>
	</table>		</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®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 7nrf" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Bam complex 3D structures\|Bam complex 3D structures]]
		+	== References ==
		+	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Escherichia coli O157:H7]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: ~~Z-disk~~]]	+	[[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]]

OCA at 08:26, 21 April 2021

OCA — Wed, 21 Apr 2021 08:26:04 GMT

←Older revision		Revision as of 08:26, 21 April 2021
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 7nrf ~~is ON HOLD~~	+	====
-		+	<StructureSection load='7nrf' size='340' side='right'caption='[[7nrf]]' scene=''>
-	~~Authors~~:	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id= OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol= FirstGlance]. <br>
-	~~Description~~:	+	</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=7nrf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7nrf OCA], [https://pdbe.org/7nrf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7nrf RCSB], [https://www.ebi.ac.uk/pdbsum/7nrf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7nrf ProSAT]</span></td></tr>
-	[[Category: ~~Unreleased~~ Structures]]	+	</table>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Large Structures]]
		+	[[Category: Z-disk]]

OCA: Protected "7nrf" [edit=sysop:move=sysop]

OCA — Wed, 10 Mar 2021 15:06:19 GMT

Protected "7nrf" [edit=sysop:move=sysop]

←Older revision

Revision as of 15:06, 10 March 2021

OCA: New page: '''Unreleased structure''' The entry 7nrf is ON HOLD Authors: Description: Category: Unreleased Structures

OCA — Wed, 10 Mar 2021 15:06:18 GMT

New page: '''Unreleased structure''' The entry 7nrf is ON HOLD Authors: Description: Category: Unreleased Structures

New page

'''Unreleased structure'''

The entry 7nrf is ON HOLD

Authors:

Description:
[[Category: Unreleased Structures]]

7nrf - Revision history

OCA at 12:38, 1 February 2024

OCA at 08:26, 21 April 2021

OCA: Protected "7nrf" [edit=sysop:move=sysop]

OCA: New page: '''Unreleased structure''' The entry 7nrf is ON HOLD Authors: Description: Category: Unreleased Structures