View source for 6xzb


==E. coli 70S ribosome in complex with dirithromycin, fMet-Phe-tRNA(Phe) and deacylated tRNA(iMet) (focused classification).==
<StructureSection load='6xzb' size='340' side='right'caption='[[6xzb]], [[Resolution|resolution]] 2.54&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6xzb]] is a 10 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli_K-12 Escherichia coli K-12]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6XZB OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6XZB 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]] 2.54&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=1MA:6-HYDRO-1-METHYLADENOSINE-5-MONOPHOSPHATE'>1MA</scene>, <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=31M:3-DEOXY-3-[(L-METHIONYL-L-PHENYLALANYL)AMINO]ADENOSINE+5-(DIHYDROGEN+PHOSPHATE)'>31M</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=4OC:4N,O2-METHYLCYTIDINE-5-MONOPHOSPHATE'>4OC</scene>, <scene name='pdbligand=4SU:4-THIOURIDINE-5-MONOPHOSPHATE'>4SU</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=D2T:(3R)-3-(METHYLSULFANYL)-L-ASPARTIC+ACID'>D2T</scene>, <scene name='pdbligand=DI0:(1~{R},2~{R},3~{R},6~{R},7~{S},8~{S},9~{R},10~{R},12~{R},13~{S},15~{R},17~{S})-9-[(2~{S},3~{R},4~{S},6~{R})-4-(dimethylamino)-6-methyl-3-oxidanyl-oxan-2-yl]oxy-3-ethyl-7-[(2~{R},4~{R},5~{S},6~{S})-4-methoxy-4,6-dimethyl-5-oxidanyl-oxan-2-yl]oxy-15-(2-methoxyethoxymethyl)-2,6,8,10,12,17-hexamethyl-2,10-bis(oxidanyl)-4,16-dioxa-14-azabicyclo[11.3.1]heptadecan-5-one'>DI0</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=M2G:N2-DIMETHYLGUANOSINE-5-MONOPHOSPHATE'>M2G</scene>, <scene name='pdbligand=MA6:6N-DIMETHYLADENOSINE-5-MONOPHOSHATE'>MA6</scene>, <scene name='pdbligand=MEQ:N5-METHYLGLUTAMINE'>MEQ</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>, <scene name='pdbligand=YYG:4-(3-[5-O-PHOSPHONORIBOFURANOSYL]-4,6-DIMETHYL-8-OXO-4,8-DIHYDRO-3H-1,3,4,5,7A-PENTAAZA-S-INDACEN-YLAMINO-BUTYRIC+ACID+METHYL+ESTER'>YYG</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=6xzb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6xzb OCA], [https://pdbe.org/6xzb PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6xzb RCSB], [https://www.ebi.ac.uk/pdbsum/6xzb PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6xzb ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/RS18_ECOLI RS18_ECOLI] Binds as a heterodimer with protein S6 to the central domain of the 16S rRNA, where it helps stabilize the platform of the 30S subunit.[HAMAP-Rule:MF_00270]
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Macrolides are one of the most successful and widely used classes of antibacterials, which kill or stop the growth of pathogenic bacteria by binding near the active site of the ribosome and interfering with protein synthesis. Dirithromycin is a derivative of the prototype macrolide erythromycin with additional hydrophobic side chain. In our recent study, we have discovered that the side chain of dirithromycin forms lone pair-pi stacking interaction with the aromatic imidazole ring of the His69 residue in ribosomal protein uL4 of the Thermus thermophilus 70S ribosome. In the current work, we found that neither the presence of the side chain, nor the additional contact with the ribosome, improve the binding affinity of dirithromycin to the ribosome. Nevertheless, we found that dirithromycin is a more potent inhibitor of in vitro protein synthesis in comparison with its parent compound, erythromycin. Using high-resolution cryo-electron microscopy, we determined the structure of the dirithromycin bound to the translating Escherichia coli 70S ribosome, which suggests that the better inhibitory properties of the drug could be rationalized by the side chain of dirithromycin pointing into the lumen of the nascent peptide exit tunnel, where it can interfere with the normal passage of the growing polypeptide chain.

Insights into the improved macrolide inhibitory activity from the high-resolution cryo-EM structure of dirithromycin bound to the E. coli 70S ribosome.,Pichkur EB, Paleskava A, Tereshchenkov AG, Kasatsky P, Komarova ES, Shiriaev DI, Bogdanov AA, Dontsova OA, Osterman IA, Sergiev PV, Polikanov YS, Myasnikov AG, Konevega AL RNA. 2020 Jun;26(6):715-723. doi: 10.1261/rna.073817.119. Epub 2020 Mar 6. PMID:32144191<ref>PMID:32144191</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6xzb" style="background-color:#fffaf0;"></div>

==See Also==
*[[Ribosome 3D structures|Ribosome 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Escherichia coli K-12]]
[[Category: Large Structures]]
[[Category: Konevega AL]]
[[Category: Myasnikov AG]]
[[Category: Pichkur EB]]
[[Category: Polikanov YS]]