8dev - Revision history

OCA at 06:08, 14 May 2025

2025-05-14T06:08:30Z

← Older revision		Revision as of 06:08, 14 May 2025
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	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[8dev]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Neisseria_gonorrhoeae Neisseria gonorrhoeae] 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=8DEV OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8DEV FirstGlance]. <br>		<table><tr><td colspan='2'>[[8dev]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Neisseria_gonorrhoeae Neisseria gonorrhoeae] 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=8DEV OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8DEV FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=DAB:2,4-DIAMINOBUTYRIC+ACID'>DAB</scene>, <scene name='pdbligand=DLE:D-LEUCINE'>DLE</scene>, <scene name='pdbligand=PTY:PHOSPHATIDYLETHANOLAMINE'>PTY</scene>, <scene name='pdbligand=RE6:(5R)-5-methylheptanoic+acid'>RE6</scene></td></tr>		</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models\|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution\|Resolution]] 3.08Å</td></tr>
			<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=DAB:2,4-DIAMINOBUTYRIC+ACID'>DAB</scene>, <scene name='pdbligand=DLE:D-LEUCINE'>DLE</scene>, <scene name='pdbligand=PTY:PHOSPHATIDYLETHANOLAMINE'>PTY</scene>, <scene name='pdbligand=RE6:(5R)-5-methylheptanoic+acid'>RE6</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=8dev FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8dev OCA], [https://pdbe.org/8dev PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8dev RCSB], [https://www.ebi.ac.uk/pdbsum/8dev PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8dev 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=8dev FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8dev OCA], [https://pdbe.org/8dev PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8dev RCSB], [https://www.ebi.ac.uk/pdbsum/8dev PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8dev ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
	[https://www.uniprot.org/uniprot/~~A0A6V7GUB3_NEIGO A0A6V7GUB3_NEIGO~~]		[https://www.uniprot.org/uniprot/Q5F725_NEIG1 Q5F725_NEIG1]
			<div style="background-color:#fffaf0;">
			== Publication Abstract from PubMed ==
			Bacterial efflux pumps in the resistance-nodulation-cell division (RND) family of Gram-negative bacteria contribute significantly to the development of antimicrobial resistance by many pathogens. In this study, we selected the MtrD transporter protein of Neisseria gonorrhoeae as it is the sole RND pump possessed by this strictly human pathogen and can export multiple antimicrobials, including antibiotics, bile salts, detergents, dyes, and antimicrobial peptides. Using knowledge from our previously published structures of MtrD in the presence or absence of bound antibiotics as a model and the known ability of MtrCDE to export cationic antimicrobial peptides, we hypothesized that cationic peptides could be accommodated within MtrD binding sites. Furthermore, we thought that MtrD-bound peptides lacking antibacterial action could sensitize bacteria to an antibiotic normally exported by the MtrCDE efflux pump or other similar RND-type pumps possessed by different Gram-negative bacteria. We now report the identification of a novel nonantimicrobial cyclic cationic antimicrobial peptide, which we termed CASP (cationic antibiotic-sensitizing peptide). By single-particle cryo-electron microscopy, we found that CASP binds within the periplasmic cleft region of MtrD using overlapping and distinct amino acid contact sites that interact with another cyclic peptide (colistin) or a linear human cationic antimicrobial peptide derived from human LL-37. While CASP could not sensitize Neisseria gonorrhoeae to an antibiotic (novobiocin) that is a substrate for RND pumps, it could do so against multiple Gram-negative, rod-shaped bacteria. We propose that CASP (or future derivatives) could serve as an adjuvant for the antibiotic treatment of certain Gram-negative infections previously thwarted by RND transporters. IMPORTANCE RND efflux pumps can export numerous antimicrobials that enter Gram-negative bacteria, and their action can reduce the efficacy of antibiotics and provide decreased susceptibility to various host antimicrobials. Here, we identified a cationic antibiotic-sensitizing peptide (CASP) that binds within the periplasmic cleft of an RND transporter protein (MtrD) produced by Neisseria gonorrhoeae. Surprisingly, CASP was able to render rod-shaped Gram-negative bacteria, but not gonococci, susceptible to an antibiotic that is a substrate for the gonococcal MtrCDE efflux pump. CASP (or its future derivatives) could be used as an adjuvant to treat infections for which RND efflux contributes to multidrug resistance.

			Structural Basis of Peptide-Based Antimicrobial Inhibition of a Resistance-Nodulation-Cell Division Multidrug Efflux Pump.,Lyu M, Ayala JC, Chirakos I, Su CC, Shafer WM, Yu EW Microbiol Spectr. 2022 Oct 26;10(5):e0299022. doi: 10.1128/spectrum.02990-22. , Epub 2022 Sep 19. PMID:36121287<ref>PMID:36121287</ref>

			From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
			</div>
			<div class="pdbe-citations 8dev" style="background-color:#fffaf0;"></div>
			== References ==
			<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>

OCA at 07:51, 9 November 2022

2022-11-09T07:51:24Z

← Older revision		Revision as of 07:51, 9 November 2022
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	</table>		</table>
	== Function ==		== Function ==
	[[https://www.uniprot.org/uniprot/A0A6V7GUB3_NEIGO A0A6V7GUB3_NEIGO]]		[https://www.uniprot.org/uniprot/A0A6V7GUB3_NEIGO A0A6V7GUB3_NEIGO]
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>

OCA at 06:59, 14 September 2022

2022-09-14T06:59:23Z

← Older revision		Revision as of 06:59, 14 September 2022
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	~~'''Unreleased structure'''~~

	~~The entry~~ 8dev is ~~ON HOLD~~		==Cryo-electron microscopy structure of Neisseria gonorrhoeae multidrug efflux pump MtrD with colistin complex==
			<StructureSection load='8dev' size='340' side='right'caption='[[8dev]], [[Resolution\|resolution]] 3.08Å' scene=''>
	~~Authors~~: ~~Lyu~~, M., Yu, E.W.		== Structural highlights ==
			<table><tr><td colspan='2'>[[8dev]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Neisseria_gonorrhoeae Neisseria gonorrhoeae] 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=8DEV OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8DEV FirstGlance]. <br>
	~~Description~~: ~~Cryo-electron microscopy structure of~~ Neisseria gonorrhoeae ~~multidrug efflux pump MtrD with colistin complex~~		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=DAB:2,4-DIAMINOBUTYRIC+ACID'>DAB</scene>, <scene name='pdbligand=DLE:D-LEUCINE'>DLE</scene>, <scene name='pdbligand=PTY:PHOSPHATIDYLETHANOLAMINE'>PTY</scene>, <scene name='pdbligand=RE6:(5R)-5-methylheptanoic+acid'>RE6</scene></td></tr>
	[[Category: ~~Unreleased Structures~~]]		<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=8dev FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8dev OCA], [https://pdbe.org/8dev PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8dev RCSB], [https://www.ebi.ac.uk/pdbsum/8dev PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8dev ProSAT]</span></td></tr>
	[[Category: Lyu, M]]		</table>
	[[Category: Yu~~, E.W~~]]		== Function ==
			[[https://www.uniprot.org/uniprot/A0A6V7GUB3_NEIGO A0A6V7GUB3_NEIGO]]
			__TOC__
			</StructureSection>
			[[Category: Large Structures]]
			[[Category: Neisseria gonorrhoeae]]
			[[Category: Synthetic construct]]
			[[Category: Lyu M]]
			[[Category: Yu EW]]

OCA: Protected "8dev" [edit=sysop:move=sysop]

2022-06-29T06:32:04Z

Protected "8dev" [edit=sysop:move=sysop]

← Older revision	Revision as of 06:32, 29 June 2022
(No difference)

OCA: New page: '''Unreleased structure''' The entry 8dev is ON HOLD Authors: Lyu, M., Yu, E.W. Description: Cryo-electron microscopy structure of Neisseria gonorrhoeae multidrug efflux pump MtrD with...

2022-06-29T06:32:02Z

New page: '''Unreleased structure''' The entry 8dev is ON HOLD Authors: Lyu, M., Yu, E.W. Description: Cryo-electron microscopy structure of Neisseria gonorrhoeae multidrug efflux pump MtrD with...

New page

'''Unreleased structure'''

The entry 8dev is ON HOLD

Authors: Lyu, M., Yu, E.W.

Description: Cryo-electron microscopy structure of Neisseria gonorrhoeae multidrug efflux pump MtrD with colistin complex
[[Category: Unreleased Structures]]
[[Category: Lyu, M]]
[[Category: Yu, E.W]]