View source for 6xqe


==Crystal structure of the Thermus thermophilus 70S ribosome in complex with sarecycline, UAA-mRNA, and deacylated P-site tRNA at 3.00A resolution==
<StructureSection load='6xqe' size='340' side='right'caption='[[6xqe]], [[Resolution|resolution]] 3.00&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6xqe]] 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=6XQE OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6XQE 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]] 3&#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=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=7MG:7N-METHYL-8-HYDROGUANOSINE-5-MONOPHOSPHATE'>7MG</scene>, <scene name='pdbligand=K:POTASSIUM+ION'>K</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=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=V7A:(4~{S},4~{a}~{S},5~{a}~{R},12~{a}~{S})-4-(dimethylamino)-7-[[methoxy(methyl)amino]methyl]-3,10,12,12~{a}-tetrakis(oxidanyl)-1,11-bis(oxidanylidene)-4~{a},5,5~{a},6-tetrahydro-4~{H}-tetracene-2-carboxamide'>V7A</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=6xqe FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6xqe OCA], [https://pdbe.org/6xqe PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6xqe RCSB], [https://www.ebi.ac.uk/pdbsum/6xqe PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6xqe ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/RL2_THET8 RL2_THET8] One of the primary rRNA binding proteins. Required for association of the 30S and 50S subunits to form the 70S ribosome, for tRNA binding and peptide bond formation. It has been suggested to have peptidyltransferase activity; this is somewhat controversial (By similarity). Makes several contacts with the 16S rRNA (forming bridge B7b) in the 70S ribosome.[HAMAP-Rule:MF_01320_B]
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Sarecycline is a new narrow-spectrum tetracycline-class antibiotic approved for the treatment of acne vulgaris. Tetracyclines share a common four-ring naphthacene core and inhibit protein synthesis by interacting with the 70S bacterial ribosome. Sarecycline is distinguished chemically from other tetracyclines because it has a 7-[[methoxy(methyl)amino]methyl] group attached at the C7 position of ring D. To investigate the functional role of this C7 moiety, we determined the X-ray crystal structure of sarecycline bound to the Thermus thermophilus 70S ribosome. Our 2.8-A resolution structure revealed that sarecycline binds at the canonical tetracycline binding site located in the decoding center of the small ribosomal subunit. Importantly, unlike other tetracyclines, the unique C7 extension of sarecycline extends into the messenger RNA (mRNA) channel to form a direct interaction with the A-site codon to possibly interfere with mRNA movement through the channel and/or disrupt A-site codon-anticodon interaction. Based on our biochemical studies, sarecycline appears to be a more potent initiation inhibitor compared to other tetracyclines, possibly due to drug interactions with the mRNA, thereby blocking accommodation of the first aminoacyl transfer RNA (tRNA) into the A site. Overall, our structural and biochemical findings rationalize the role of the unique C7 moiety of sarecycline in antibiotic action.

Sarecycline interferes with tRNA accommodation and tethers mRNA to the 70S ribosome.,Batool Z, Lomakin IB, Polikanov YS, Bunick CG Proc Natl Acad Sci U S A. 2020 Aug 25;117(34):20530-20537. doi:, 10.1073/pnas.2008671117. Epub 2020 Aug 12. PMID:32817463<ref>PMID:32817463</ref>

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

==See Also==
*[[Ribosome 3D structures|Ribosome 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Thermus thermophilus HB8]]
[[Category: Batool Z]]
[[Category: Bunick CG]]
[[Category: Lomakin IB]]
[[Category: Polikanov YS]]