View source for 8fr3


==E. coli EF-Tu in complex with KKL-55==
<StructureSection load='8fr3' size='340' side='right'caption='[[8fr3]], [[Resolution|resolution]] 2.23&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[8fr3]] is a 2 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=8FR3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8FR3 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]] 2.23&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GDP:GUANOSINE-5-DIPHOSPHATE'>GDP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=Y7C:3-chloro-N-(1-propyl-1H-tetrazol-5-yl)benzamide'>Y7C</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=8fr3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8fr3 OCA], [https://pdbe.org/8fr3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8fr3 RCSB], [https://www.ebi.ac.uk/pdbsum/8fr3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8fr3 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/E2QFJ4_ECOLX E2QFJ4_ECOLX] This protein promotes the GTP-dependent binding of aminoacyl-tRNA to the A-site of ribosomes during protein biosynthesis.[HAMAP-Rule:MF_00118]
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
trans-Translation is conserved throughout bacteria and is essential in many species. High-throughput screening identified a tetrazole-based trans-translation inhibitor, KKL-55, that has broad-spectrum antibiotic activity. A biotinylated version of KKL-55 pulled down elongation factor thermo-unstable (EF-Tu) from bacterial lysates. Purified EF-Tu bound KKL-55 in vitro with a K (d) = 2 microM, confirming a high-affinity interaction. An X-ray crystal structure showed that KKL-55 binds in domain 3 of EF-Tu, and mutation of residues in the binding pocket abolished KKL-55 binding. RNA-binding assays in vitro showed that KKL-55 inhibits binding between EF-Tu and transfer-messenger RNA (tmRNA) but not between EF-Tu and tRNA. These data demonstrate a new mechanism for the inhibition of EF-Tu function and suggest that this specific inhibition of EF-Tu*tmRNA binding is a viable target for antibiotic development. IMPORTANCE Elongation factor thermo-unstable (EF-Tu) is a universally conserved translation factor that mediates productive interactions between tRNAs and the ribosome. In bacteria, EF-Tu also delivers transfer-messenger RNA (tmRNA)-SmpB to the ribosome during trans-translation. We report the first small molecule, KKL-55, that specifically inhibits EF-Tu activity in trans-translation without affecting its activity in normal translation. KKL-55 has broad-spectrum antibiotic activity, suggesting that compounds targeted to the tmRNA-binding interface of EF-Tu could be developed into new antibiotics to treat drug-resistant infections.

Antibiotic that inhibits trans-translation blocks binding of EF-Tu to tmRNA but not to tRNA.,Marathe N, Nguyen HA, Alumasa JN, Kuzmishin Nagy AB, Vazquez M, Dunham CM, Keiler KC mBio. 2023 Sep 8:e0146123. doi: 10.1128/mbio.01461-23. PMID:37681945<ref>PMID:37681945</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 8fr3" style="background-color:#fffaf0;"></div>
== References ==
<references/>
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</StructureSection>
[[Category: Escherichia coli K-12]]
[[Category: Large Structures]]
[[Category: Dunham CM]]
[[Category: Kuzmishin Nagy AB]]
[[Category: Nguyen HA]]