View source for 9dfc


==Crystal structure of the wild-type Thermus thermophilus 70S ribosome in complex with lasso peptide lariocidin, mRNA, aminoacylated A-site Phe-tRNAphe, aminoacylated P-site fMet-tRNAmet, and deacylated E-site tRNAphe at 2.50A resolution==
<StructureSection load='9dfc' size='340' side='right'caption='[[9dfc]], [[Resolution|resolution]] 2.50&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[9dfc]] 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=9DFC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9DFC 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]] 2.5&#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=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=F3N:3-DEOXY-3-(L-PHENYLALANYLAMINO)ADENOSINE+5-(DIHYDROGEN+PHOSPHATE)'>F3N</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=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=9dfc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9dfc OCA], [https://pdbe.org/9dfc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9dfc RCSB], [https://www.ebi.ac.uk/pdbsum/9dfc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9dfc ProSAT]</span></td></tr>
</table>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Lasso peptides, biologically active molecules with a distinct structurally constrained knotted fold, are natural products belonging to the class of ribosomally-synthesized and posttranslationally modified peptides (RiPPs). Lasso peptides act upon several bacterial targets, but none have been reported to inhibit the ribosome, one of the main antibiotic targets in the bacterial cell. Here, we report the identification and characterization of the lasso peptide antibiotic, lariocidin (LAR), and its internally cyclized derivative, lariocidin B (LAR-B), produced by Paenabacillussp. M2, with broad-spectrum activity against many bacterial pathogens. We show that lariocidins inhibit bacterial growth by binding to the ribosome and interfering with protein synthesis. Structural, genetic, and biochemical data show that lariocidins bind at a unique site in the small ribosomal subunit, where they interact with the 16S rRNA and aminoacyl-tRNA, inhibiting translocation and inducing miscoding. LAR is unaffected by common resistance mechanisms, has a low propensity for generating spontaneous resistance, shows no human cell toxicity, and has potent in vivo activity in a mouse model of Acinetobacter baumannii infection. Our finding of the first ribosome-targeting lasso peptides uncovers new routes toward discovering alternative protein synthesis inhibitors and offers a new chemical scaffold for developing much-needed antibacterial drugs.

A Broad Spectrum Lasso Peptide Antibiotic Targeting the Bacterial Ribosome.,Wright G, Jangra M, Travin D, Aleksandrova E, Kaur M, Darwish L, Koteva K, Klepacki D, Wang W, Tiffany M, Sokaribo A, Coombes B, Vazquez-Laslop N, Polikanov Y, Mankin A Res Sq [Preprint]. 2024 Sep 16:rs.3.rs-5058118. doi: 10.21203/rs.3.rs-5058118/v1. PMID:39372947<ref>PMID:39372947</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 9dfc" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Thermus thermophilus HB8]]
[[Category: Aleksandrova EV]]
[[Category: Coombes BK]]
[[Category: Darwish L]]
[[Category: Jangra M]]
[[Category: Kaur M]]
[[Category: Klepacki D]]
[[Category: Koteva K]]
[[Category: Mankin AS]]
[[Category: Polikanov YS]]
[[Category: Sokaribo A]]
[[Category: Tiffany M]]
[[Category: Travin DY]]
[[Category: Vazquez-Laslop N]]
[[Category: Wang W]]
[[Category: Wright GD]]