8fc1: Difference between revisions

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-'''Unreleased structure'''
-The entry 8fc1 is ON HOLD
+==Crystal structure of the Thermus thermophilus 70S ribosome in complex with protein Y, hygromycin A, and erythromycin at 2.50A resolution==
+<StructureSection load='8fc1' size='340' side='right'caption='[[8fc1]], [[Resolution|resolution]] 2.50&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[8fc1]] 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=8FC1 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8FC1 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]] 2.5&#8491;</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=2MU:2,5-DIMETHYLURIDINE-5-MONOPHOSPHATE'>2MU</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=PSU:PSEUDOURIDINE-5-MONOPHOSPHATE'>PSU</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=8fc1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8fc1 OCA], [https://pdbe.org/8fc1 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8fc1 RCSB], [https://www.ebi.ac.uk/pdbsum/8fc1 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8fc1 ProSAT]</span></td></tr>
+</table>
+== Function ==
+[https://www.uniprot.org/uniprot/RL3_THET8 RL3_THET8] One of the primary rRNA binding proteins, it binds directly near the 3'-end of the 23S rRNA, where it nucleates assembly of the 50S subunit (By similarity).[HAMAP-Rule:MF_01325_B]
+<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 Thermus thermophilus 70S ribosome in complex with protein Y, hygromycin A, and erythromycin at 2.50A resolution
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
-[[Category: Polikanov, Y.S]]
+<div class="pdbe-citations 8fc1" style="background-color:#fffaf0;"></div>
-[[Category: Syroegin, E.A]]
-[[Category: Chen, C.-W]]
+==See Also==
-[[Category: Svetlov, M.S]]
+*[[Ribosomal protein THX 3D structures|Ribosomal protein THX 3D structures]]
+*[[Ribosome 3D structures|Ribosome 3D structures]]
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Large Structures]]
+[[Category: Thermus thermophilus HB8]]
+[[Category: Chen C-W]]
+[[Category: Polikanov YS]]
+[[Category: Svetlov MS]]
+[[Category: Syroegin EA]]