OCA at 12:37, 26 July 2023

2023-07-26T12:37:55Z

←Older revision		Revision as of 12:37, 26 July 2023
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-	'''Unreleased structure'''

-	~~The entry~~ 8fc4 is ~~ON HOLD~~	+	==Crystal structure of the A2058-N6-dimethylated Thermus thermophilus 70S ribosome in complex with protein Y, hygromycin A, and erythromycin at 2.45A resolution==
		+	<StructureSection load='8fc4' size='340' side='right'caption='[[8fc4]], [[Resolution\|resolution]] 2.45Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[8fc4]] is a 20 chain structure with sequence from [https://en.wikipedia.org/wiki/Thermus_thermophilus_HB8 Thermus thermophilus HB8]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8FC4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8FC4 FirstGlance]. <br>
		+	</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models\|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution\|Resolution]] 2.45Å</td></tr>
		+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=0TD:(3S)-3-(METHYLSULFANYL)-L-ASPARTIC+ACID'>0TD</scene>, <scene name='pdbligand=2MA:2-METHYLADENOSINE-5-MONOPHOSPHATE'>2MA</scene>, <scene name='pdbligand=2MG:2N-METHYLGUANOSINE-5-MONOPHOSPHATE'>2MG</scene>, <scene name='pdbligand=4OC:4N,O2-METHYLCYTIDINE-5-MONOPHOSPHATE'>4OC</scene>, <scene name='pdbligand=5MC:5-METHYLCYTIDINE-5-MONOPHOSPHATE'>5MC</scene>, <scene name='pdbligand=5MU:5-METHYLURIDINE+5-MONOPHOSPHATE'>5MU</scene>, <scene name='pdbligand=ARG:ARGININE'>ARG</scene>, <scene name='pdbligand=ERY:ERYTHROMYCIN+A'>ERY</scene>, <scene name='pdbligand=G7M:N7-METHYL-GUANOSINE-5-MONOPHOSPHATE'>G7M</scene>, <scene name='pdbligand=HGR:HYGROMYCIN+A'>HGR</scene>, <scene name='pdbligand=M2G:N2-DIMETHYLGUANOSINE-5-MONOPHOSPHATE'>M2G</scene>, <scene name='pdbligand=MA6:6N-DIMETHYLADENOSINE-5-MONOPHOSHATE'>MA6</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=MPD:(4S)-2-METHYL-2,4-PENTANEDIOL'>MPD</scene>, <scene name='pdbligand=OMC:O2-METHYLYCYTIDINE-5-MONOPHOSPHATE'>OMC</scene>, <scene name='pdbligand=OMG:O2-METHYLGUANOSINE-5-MONOPHOSPHATE'>OMG</scene>, <scene name='pdbligand=OMU:O2-METHYLURIDINE+5-MONOPHOSPHATE'>OMU</scene>, <scene name='pdbligand=PSU:PSEUDOURIDINE-5-MONOPHOSPHATE'>PSU</scene>, <scene name='pdbligand=SF4:IRON/SULFUR+CLUSTER'>SF4</scene>, <scene name='pdbligand=UR3:3-METHYLURIDINE-5-MONOPHOSHATE'>UR3</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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=8fc4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8fc4 OCA], [https://pdbe.org/8fc4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8fc4 RCSB], [https://www.ebi.ac.uk/pdbsum/8fc4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8fc4 ProSAT]</span></td></tr>
		+	</table>
		+	== Function ==
		+	[https://www.uniprot.org/uniprot/RL34_THET8 RL34_THET8] Found on the solvent side of the large subunit.[HAMAP-Rule:MF_00391]
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	The ever-growing rise of antibiotic resistance among bacterial pathogens is one of the top healthcare threats today. Although combination antibiotic therapies represent a potential approach to more efficiently combat infections caused by susceptible and drug-resistant bacteria, only a few known drug pairs exhibit synergy/cooperativity in killing bacteria. Here, we discover that well-known ribosomal antibiotics, hygromycin A (HygA) and macrolides, which target peptidyl transferase center and peptide exit tunnel, respectively, can act cooperatively against susceptible and drug-resistant bacteria. Remarkably, HygA slows down macrolide dissociation from the ribosome by 60-fold and enhances the otherwise weak antimicrobial activity of the newest-generation macrolide drugs known as ketolides against macrolide-resistant bacteria. By determining a set of high-resolution X-ray crystal structures of drug-sensitive wild-type and macrolide-resistant Erm-methylated 70S ribosomes in complex with three HygA-macrolide pairs, we provide a structural rationale for the binding cooperativity of these drugs and also uncover the molecular mechanism of overcoming Erm-type resistance by macrolides acting together with hygromycin A. Altogether our structural, biochemical, and microbiological findings lay the foundation for the subsequent development of synergistic antibiotic tandems with improved bactericidal properties against drug-resistant pathogens, including those expressing erm genes.

-	~~Authors: Chen, C.~~-W., Syroegin, ~~E.A.~~, ~~Svetlov~~, ~~M.S.~~, Polikanov, Y.S.	+	Structural insights into the mechanism of overcoming Erm-mediated resistance by macrolides acting together with hygromycin-A.,Chen CW, Leimer N, Syroegin EA, Dunand C, Bulman ZP, Lewis K, Polikanov YS, Svetlov MS Nat Commun. 2023 Jul 14;14(1):4196. doi: 10.1038/s41467-023-39653-5. PMID:37452045<ref>PMID:37452045</ref>

-	~~Description: Crystal structure~~ of the ~~A2058~~-N6-~~dimethylated Thermus thermophilus 70S ribosome in complex with protein Y, hygromycin A, and erythromycin at 2.45A resolution~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	[[Category: ~~Unreleased~~ Structures]]	+	</div>
-	[[Category: ~~Polikanov, Y.S~~]]	+	<div class="pdbe-citations 8fc4" style="background-color:#fffaf0;"></div>
-	[[Category: ~~Syroegin, E.A~~]]	+	== References ==
-	[[Category: ~~Chen, C.-W~~]]	+	<references/>
-	[[Category: Svetlov~~, M.S~~]]	+	__TOC__
		+	</StructureSection>
		+	[[Category: Large Structures]]
		+	[[Category: Thermus thermophilus HB8]]
		+	[[Category: Chen C-W]]
		+	[[Category: Polikanov YS]]
		+	[[Category: Svetlov MS]]
		+	[[Category: Syroegin EA]]

OCA: Protected "8fc4" [edit=sysop:move=sysop]

2022-12-07T05:42:31Z

Protected "8fc4" [edit=sysop:move=sysop]

←Older revision

Revision as of 05:42, 7 December 2022

OCA: New page: '''Unreleased structure''' The entry 8fc4 is ON HOLD Authors: Chen, C.-W., Syroegin, E.A., Svetlov, M.S., Polikanov, Y.S. Description: Crystal structure of the A2058-N6-dimethylated Th...

2022-12-07T05:42:28Z

New page: '''Unreleased structure''' The entry 8fc4 is ON HOLD Authors: Chen, C.-W., Syroegin, E.A., Svetlov, M.S., Polikanov, Y.S. Description: Crystal structure of the A2058-N6-dimethylated Th...

New page

'''Unreleased structure'''

The entry 8fc4 is ON HOLD

Authors: Chen, C.-W., Syroegin, E.A., Svetlov, M.S., Polikanov, Y.S.

Description: Crystal structure of the A2058-N6-dimethylated Thermus thermophilus 70S ribosome in complex with protein Y, hygromycin A, and erythromycin at 2.45A resolution
[[Category: Unreleased Structures]]
[[Category: Polikanov, Y.S]]
[[Category: Syroegin, E.A]]
[[Category: Chen, C.-W]]
[[Category: Svetlov, M.S]]

8fc4 - Revision history

OCA at 12:37, 26 July 2023

OCA: Protected "8fc4" [edit=sysop:move=sysop]

OCA: New page: '''Unreleased structure''' The entry 8fc4 is ON HOLD Authors: Chen, C.-W., Syroegin, E.A., Svetlov, M.S., Polikanov, Y.S. Description: Crystal structure of the A2058-N6-dimethylated Th...