View source for 5kcs


==Cryo-EM structure of the Escherichia coli 70S ribosome in complex with antibiotic Evernimycin, mRNA, TetM and P-site tRNA at 3.9A resolution==
<SX load='5kcs' size='340' side='right' viewer='molstar' caption='[[5kcs]], [[Resolution|resolution]] 3.90&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5kcs]] is a 10 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli_K-12 Escherichia coli K-12] 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=5KCS OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5KCS 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]] 3.9&#8491;</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=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=6MZ:N6-METHYLADENOSINE-5-MONOPHOSPHATE'>6MZ</scene>, <scene name='pdbligand=7MG:7N-METHYL-8-HYDROGUANOSINE-5-MONOPHOSPHATE'>7MG</scene>, <scene name='pdbligand=EVN:(2R,3R,4R,6S)-6-{[(2R,3AR,4R,4R,5S,6S,6R,7S,7AR)-6-{[(2S,3R,4R,5S,6R)-2-{[(2R,3S,4S,5S,6S)-6-({(2R,3AS,3AR,6S,7R,7R,7AS,7AS)-7-[(2,4-DIHYDROXY-6-METHYLBENZOYL)OXY]-7-HYDROXYOCTAHYDRO-4H-2,4-SPIROBI[[1,3]DIOXOLO[4,5-C]PYRAN]-6-YL}OXY)-4-HYDROXY-5-METHOXY-2-(METHOXYMETHYL)TETRAHYDRO-2H-PYRAN-3-YL]OXY}-3-HYDROXY-5-METHOXY-6-METHYLTETRAHYDRO-2H-PYRAN-4-YL]OXY}-4,7-DIHYDROXY-4,6,7A-TRIMETHYLOCTAHYDRO-4H-SPIRO[1,3-DIOXOLO[4,5-C]PYRAN-2,2-PYRAN]-5-YL]OXY}-4-{[(2R,4S,5R,6S)-5-METHOXY-4,6-DIMETHYL-4-NITROTETRAHYDRO-2H-PYRAN-2-YL]OXY}-2-METHYLTETRAHYDRO-2H-PYRAN-3-YL+3,5-DICHLORO-4-HYDROXY-2-METHOXY-6-METHYLBENZOATE+(NON-PREFERRED+NAME)'>EVN</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=MA6:6N-DIMETHYLADENOSINE-5-MONOPHOSHATE'>MA6</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=UR3:3-METHYLURIDINE-5-MONOPHOSHATE'>UR3</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=5kcs FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5kcs OCA], [https://pdbe.org/5kcs PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5kcs RCSB], [https://www.ebi.ac.uk/pdbsum/5kcs PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5kcs ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/RL32_ECOLI RL32_ECOLI] 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The ribosome is one of the major targets for therapeutic antibiotics; however, the rise in multidrug resistance is a growing threat to the utility of our current arsenal. The orthosomycin antibiotics evernimicin (EVN) and avilamycin (AVI) target the ribosome and do not display cross-resistance with any other classes of antibiotics, suggesting that they bind to a unique site on the ribosome and may therefore represent an avenue for development of new antimicrobial agents. Here we present cryo-EM structures of EVN and AVI in complex with the Escherichia coli ribosome at 3.6- to 3.9-A resolution. The structures reveal that EVN and AVI bind to a single site on the large subunit that is distinct from other known antibiotic binding sites on the ribosome. Both antibiotics adopt an extended conformation spanning the minor grooves of helices 89 and 91 of the 23S rRNA and interacting with arginine residues of ribosomal protein L16. This binding site overlaps with the elbow region of A-site bound tRNA. Consistent with this finding, single-molecule FRET (smFRET) experiments show that both antibiotics interfere with late steps in the accommodation process, wherein aminoacyl-tRNA enters the peptidyltransferase center of the large ribosomal subunit. These data provide a structural and mechanistic rationale for how these antibiotics inhibit the elongation phase of protein synthesis.

Structures of the orthosomycin antibiotics avilamycin and evernimicin in complex with the bacterial 70S ribosome.,Arenz S, Juette MF, Graf M, Nguyen F, Huter P, Polikanov YS, Blanchard SC, Wilson DN Proc Natl Acad Sci U S A. 2016 Jul 5;113(27):7527-32. doi:, 10.1073/pnas.1604790113. Epub 2016 Jun 21. PMID:27330110<ref>PMID:27330110</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 5kcs" style="background-color:#fffaf0;"></div>

==See Also==
*[[Ribosome 3D structures|Ribosome 3D structures]]
== References ==
<references/>
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</SX>
[[Category: Escherichia coli K-12]]
[[Category: Large Structures]]
[[Category: Synthetic construct]]
[[Category: Arenz S]]
[[Category: Blanchard SC]]
[[Category: Graf M]]
[[Category: Huter P]]
[[Category: Juette MF]]
[[Category: Nguyen F]]
[[Category: Polikanov YS]]
[[Category: Wilson DN]]