View source for 9qqq


==Cryo-EM structure of SKM-70S ribosomal stalled complex in the major state (vacant A-site, canon)==
<StructureSection load='9qqq' size='340' side='right'caption='[[9qqq]], [[Resolution|resolution]] 2.26&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[9qqq]] is a 10 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli_B Escherichia coli B]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=9QQQ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9QQQ 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]] 2.26&#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=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=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=A1JA7:[(2~{S},3~{S},4~{R},5~{R},6~{S})-4-[(2~{S},3~{R},4~{S},5~{R},6~{S})-5-acetamido-6-(hydroxymethyl)-4-[(2~{R},3~{R},4~{S},5~{S},6~{R})-6-(hydroxymethyl)-4-[(2~{S},3~{R},4~{R},5~{R},6~{R})-6-(hydroxymethyl)-5-methoxy-3,4-bis(oxidanyl)oxan-2-yl]oxy-3,5-bis(oxidanyl)oxan-2-yl]oxy-3-oxidanyl-oxan-2-yl]oxy-6-carbamimidamido-2-(hydroxymethyl)-5-oxidanyl-oxan-3-yl]+carbamate'>A1JA7</scene>, <scene name='pdbligand=D2T:(3R)-3-(METHYLSULFANYL)-L-ASPARTIC+ACID'>D2T</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=IAS:BETA-L-ASPARTIC+ACID'>IAS</scene>, <scene name='pdbligand=MA6:6N-DIMETHYLADENOSINE-5-MONOPHOSHATE'>MA6</scene>, <scene name='pdbligand=MEQ:N5-METHYLGLUTAMINE'>MEQ</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=MS6:(2S)-2-amino-4-(methylsulfanyl)butane-1-thiol'>MS6</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=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=9qqq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9qqq OCA], [https://pdbe.org/9qqq PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9qqq RCSB], [https://www.ebi.ac.uk/pdbsum/9qqq PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9qqq ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/RL33_ECOLI RL33_ECOLI] 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Tuberculosis is the deadliest bacterial disease on the planet. The months-long regimen of multiple antibiotics required to treat tuberculosis profoundly affects the microbiome and leads to the development of antimicrobial resistance. Furthermore, non-tuberculous mycobacterial infections pose an increasing clinical challenge. Consequently, there is a growing need for new narrow-spectrum mycobacteria-targeting antibiotics with different mechanisms of action. Here, we report the discovery and characterization of a natural glycolipid antibiotic, saskemycin (SKM), which demonstrates potent and highly selective activity against mycobacteria. Genome sequencing, chemical analysis, and isotope feeding strategies reveal the unique structure and biosynthetic origin of SKM. SKM binds to the small ribosomal subunit at a site not targeted by any of the clinically relevant antibiotics acting on the ribosome. Bound to the ribosome, SKM corrupts the decoding center in a unique way, preventing stable binding of aminoacyl-tRNA in the A site and inhibiting translation in a sequence context-specific manner. Self-resistance in the producing organism is conferred by methylation of a single 16S rRNA nucleotide by SasO and SasN rRNA methyltransferases. These enzymes are orthologs of the ubiquitous RsmC and SpoU methyltransferases found in most bacterial genera but absent in mycobacteria, rationalizing SKM's exquisite selectivity. The discovery of SKM provides an entry point for the development of selective, microbiome-sparing antimycobacterial antibiotics with a unique structure, binding site, and mechanism of action.

Saskemycin, a potent and selective antimycobacterial agent targeting a unique site on the ribosome.,Wright G, Cook M, Xu M, Morici M, Travin D, Wang W, Klepacki D, Chhabra N, Rao V, Sahile H, Hackenberger D, Safdari H, Berger M, Corazza M, Bond A, Guitor A, Tertigas D, Wang L, Schaenzer A, Ejim L, Yarlagadda V, Gomez J, Surette M, Av-Gay Y, Dhar N, Hung D, Vazquez-Laslop N, Mankin A, Wilson D Res Sq [Preprint]. 2025 Nov 7:rs.3.rs-7820265. doi: 10.21203/rs.3.rs-7820265/v1. PMID:41282059<ref>PMID:41282059</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 9qqq" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Escherichia coli B]]
[[Category: Large Structures]]
[[Category: Corazza M]]
[[Category: Morici M]]
[[Category: Safdari HA]]
[[Category: Wilson DN]]