7s1g: Difference between revisions
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==wild-type Escherichia coli stalled ribosome with antibiotic linezolid== | |||
<StructureSection load='7s1g' size='340' side='right'caption='[[7s1g]], [[Resolution|resolution]] 2.48Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[7s1g]] is a 10 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7S1G OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7S1G 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]] 2.48Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=1MG:1N-METHYLGUANOSINE-5-MONOPHOSPHATE'>1MG</scene>, <scene name='pdbligand=2MA:2-METHYLADENOSINE-5-MONOPHOSPHATE'>2MA</scene>, <scene name='pdbligand=2MG:2N-METHYLGUANOSINE-5-MONOPHOSPHATE'>2MG</scene>, <scene name='pdbligand=3TD:(1S)-1,4-ANHYDRO-1-(3-METHYL-2,4-DIOXO-1,2,3,4-TETRAHYDROPYRIMIDIN-5-YL)-5-O-PHOSPHONO-D-RIBITOL'>3TD</scene>, <scene name='pdbligand=4D4:(2S,3R)-2-AZANYL-5-CARBAMIMIDAMIDO-3-OXIDANYL-PENTANOIC+ACID'>4D4</scene>, <scene name='pdbligand=5MC:5-METHYLCYTIDINE-5-MONOPHOSPHATE'>5MC</scene>, <scene name='pdbligand=5MU:5-METHYLURIDINE+5-MONOPHOSPHATE'>5MU</scene>, <scene name='pdbligand=6MZ:N6-METHYLADENOSINE-5-MONOPHOSPHATE'>6MZ</scene>, <scene name='pdbligand=G7M:N7-METHYL-GUANOSINE-5-MONOPHOSPHATE'>G7M</scene>, <scene name='pdbligand=H2U:5,6-DIHYDROURIDINE-5-MONOPHOSPHATE'>H2U</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</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=ZLD:N-{[(5S)-3-(3-FLUORO-4-MORPHOLIN-4-YLPHENYL)-2-OXO-1,3-OXAZOLIDIN-5-YL]METHYL}ACETAMIDE'>ZLD</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=7s1g FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7s1g OCA], [https://pdbe.org/7s1g PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7s1g RCSB], [https://www.ebi.ac.uk/pdbsum/7s1g PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7s1g ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/RL23_ECOLI RL23_ECOLI] One of the early assembly proteins, it binds 23S rRNA; is essential for growth. One of the proteins that surround the polypeptide exit tunnel on the outside of the subunit. Acts as the docking site for trigger factor (PubMed:12226666) for Ffh binding to the ribosome (SRP54, PubMed:12756233 and PubMed:12702815) and to nascent polypeptide chains (PubMed:12756233).[HAMAP-Rule:MF_01369] | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
The antibiotic linezolid, the first clinically approved member of the oxazolidinone class, inhibits translation of bacterial ribosomes by binding to the peptidyl transferase center. Recent work has demonstrated that linezolid does not inhibit peptide bond formation at all sequences but rather acts in a context-specific manner, namely when alanine occupies the penultimate position of the nascent chain. However, the molecular basis for context-specificity has not been elucidated. Here we show that the second-generation oxazolidinone radezolid also induces stalling with a penultimate alanine, and we determine high-resolution cryo-EM structures of linezolid- and radezolid-stalled ribosome complexes to explain their mechanism of action. These structures reveal that the alanine side chain fits within a small hydrophobic crevice created by oxazolidinone, resulting in improved ribosome binding. Modification of the ribosome by the antibiotic resistance enzyme Cfr disrupts stalling due to repositioning of the modified nucleotide. Together, our findings provide molecular understanding for the context-specificity of oxazolidinones. | |||
Structural basis for context-specific inhibition of translation by oxazolidinone antibiotics.,Tsai K, Stojkovic V, Lee DJ, Young ID, Szal T, Klepacki D, Vazquez-Laslop N, Mankin AS, Fraser JS, Fujimori DG Nat Struct Mol Biol. 2022 Feb;29(2):162-171. doi: 10.1038/s41594-022-00723-9. , Epub 2022 Feb 14. PMID:35165456<ref>PMID:35165456</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: | <div class="pdbe-citations 7s1g" style="background-color:#fffaf0;"></div> | ||
[[Category: Fraser | |||
[[Category: | ==See Also== | ||
[[Category: Lee | *[[Ribosome 3D structures|Ribosome 3D structures]] | ||
[[Category: | == References == | ||
[[Category: Tsai | <references/> | ||
__TOC__ | |||
</StructureSection> | |||
[[Category: Escherichia coli]] | |||
[[Category: Large Structures]] | |||
[[Category: Fraser JS]] | |||
[[Category: Galonic Fujimori D]] | |||
[[Category: Lee DJ]] | |||
[[Category: Stojkovic V]] | |||
[[Category: Tsai K]] | |||
[[Category: Young ID]] | |||
Latest revision as of 14:11, 15 November 2023
wild-type Escherichia coli stalled ribosome with antibiotic linezolidwild-type Escherichia coli stalled ribosome with antibiotic linezolid
Structural highlights
FunctionRL23_ECOLI One of the early assembly proteins, it binds 23S rRNA; is essential for growth. One of the proteins that surround the polypeptide exit tunnel on the outside of the subunit. Acts as the docking site for trigger factor (PubMed:12226666) for Ffh binding to the ribosome (SRP54, PubMed:12756233 and PubMed:12702815) and to nascent polypeptide chains (PubMed:12756233).[HAMAP-Rule:MF_01369] Publication Abstract from PubMedThe antibiotic linezolid, the first clinically approved member of the oxazolidinone class, inhibits translation of bacterial ribosomes by binding to the peptidyl transferase center. Recent work has demonstrated that linezolid does not inhibit peptide bond formation at all sequences but rather acts in a context-specific manner, namely when alanine occupies the penultimate position of the nascent chain. However, the molecular basis for context-specificity has not been elucidated. Here we show that the second-generation oxazolidinone radezolid also induces stalling with a penultimate alanine, and we determine high-resolution cryo-EM structures of linezolid- and radezolid-stalled ribosome complexes to explain their mechanism of action. These structures reveal that the alanine side chain fits within a small hydrophobic crevice created by oxazolidinone, resulting in improved ribosome binding. Modification of the ribosome by the antibiotic resistance enzyme Cfr disrupts stalling due to repositioning of the modified nucleotide. Together, our findings provide molecular understanding for the context-specificity of oxazolidinones. Structural basis for context-specific inhibition of translation by oxazolidinone antibiotics.,Tsai K, Stojkovic V, Lee DJ, Young ID, Szal T, Klepacki D, Vazquez-Laslop N, Mankin AS, Fraser JS, Fujimori DG Nat Struct Mol Biol. 2022 Feb;29(2):162-171. doi: 10.1038/s41594-022-00723-9. , Epub 2022 Feb 14. PMID:35165456[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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