View source for 8ud8


==Crystal structure of the A2503-C2,C8-dimethylated Thermus thermophilus 70S ribosome in complex with cresomycin, mRNA, deacylated A-site tRNAphe, aminoacylated P-site fMet-tRNAmet, and deacylated E-site tRNAphe at 2.70A resolution==
<StructureSection load='8ud8' size='340' side='right'caption='[[8ud8]], [[Resolution|resolution]] 2.60&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[8ud8]] is a 22 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli], [https://en.wikipedia.org/wiki/Escherichia_virus_T4 Escherichia virus T4] and [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=8UD8 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8UD8 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]] 2.6&#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=2MG:2N-METHYLGUANOSINE-5-MONOPHOSPHATE'>2MG</scene>, <scene name='pdbligand=31H:3-DEOXY-3-[(N-FORMYL-L-METHIONYL)AMINO]ADENOSINE+5-(DIHYDROGEN+PHOSPHATE)'>31H</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=8AH:2,8-dimethyladenosine+5-(dihydrogen+phosphate)'>8AH</scene>, <scene name='pdbligand=G7M:N7-METHYL-GUANOSINE-5-MONOPHOSPHATE'>G7M</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=MIA:2-METHYLTHIO-N6-ISOPENTENYL-ADENOSINE-5-MONOPHOSPHATE'>MIA</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=WC9:(4~{S},5~{a}~{S},8~{S},8~{a}~{R})-4-(2-methylpropyl)-~{N}-[(1~{R},5~{Z},7~{R},8~{R},9~{R},10~{R},11~{S},12~{R})-7-methyl-10,11,12-tris(oxidanyl)-13-oxa-2-thiabicyclo[7.3.1]tridec-5-en-8-yl]-3,4,5,5~{a},6,7,8,8~{a}-octahydro-2~{H}-oxepino[2,3-c]pyrrole-8-carboxamide'>WC9</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=8ud8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8ud8 OCA], [https://pdbe.org/8ud8 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8ud8 RCSB], [https://www.ebi.ac.uk/pdbsum/8ud8 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8ud8 ProSAT]</span></td></tr>
</table>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
We report the design conception, chemical synthesis, and microbiological evaluation of the bridged macrobicyclic antibiotic cresomycin (CRM), which overcomes evolutionarily diverse forms of antimicrobial resistance that render modern antibiotics ineffective. CRM exhibits in vitro and in vivo efficacy against both Gram-positive and Gram-negative bacteria, including multidrug-resistant strains of Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. We show that CRM is highly preorganized for ribosomal binding by determining its density functional theory-calculated, solution-state, solid-state, and (wild-type) ribosome-bound structures, which all align identically within the macrobicyclic subunits. Lastly, we report two additional x-ray crystal structures of CRM in complex with bacterial ribosomes separately modified by the ribosomal RNA methylases, chloramphenicol-florfenicol resistance (Cfr) and erythromycin-resistance ribosomal RNA methylase (Erm), revealing concessive adjustments by the target and antibiotic that permit CRM to maintain binding where other antibiotics fail.

An antibiotic preorganized for ribosomal binding overcomes antimicrobial resistance.,Wu KJY, Tresco BIC, Ramkissoon A, Aleksandrova EV, Syroegin EA, See DNY, Liow P, Dittemore GA, Yu M, Testolin G, Mitcheltree MJ, Liu RY, Svetlov MS, Polikanov YS, Myers AG Science. 2024 Feb 16;383(6684):721-726. doi: 10.1126/science.adk8013. Epub 2024 , Feb 15. PMID:38359125<ref>PMID:38359125</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 8ud8" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Escherichia coli]]
[[Category: Escherichia virus T4]]
[[Category: Large Structures]]
[[Category: Thermus thermophilus HB8]]
[[Category: Aleksandrova EV]]
[[Category: Dittemore GA]]
[[Category: Liow P]]
[[Category: Liu RY]]
[[Category: Mitcheltree MJ]]
[[Category: Myers AG]]
[[Category: Polikanov YS]]
[[Category: Ramkissoon A]]
[[Category: See DNY]]
[[Category: Svetlov MS]]
[[Category: Syroegin EA]]
[[Category: Testolin G]]
[[Category: Tresco BIC]]
[[Category: Wu KJY]]
[[Category: Yu M]]