View source for 8xt1


==Cryo-EM structure of the human 39S mitoribosome with 5uM Tigecycline==
<StructureSection load='8xt1' size='340' side='right'caption='[[8xt1]], [[Resolution|resolution]] 3.10&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[8xt1]] is a 10 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8XT1 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8XT1 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]] 3.1&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=T1C:TIGECYCLINE'>T1C</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=8xt1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8xt1 OCA], [https://pdbe.org/8xt1 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8xt1 RCSB], [https://www.ebi.ac.uk/pdbsum/8xt1 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8xt1 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/RM02_HUMAN RM02_HUMAN] 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Tigecycline is widely used for treating complicated bacterial infections for which there are no effective drugs. It inhibits bacterial protein translation by blocking the ribosomal A-site. However, even though it is also cytotoxic for human cells, the molecular mechanism of its inhibition remains unclear. Here, we present cryo-EM structures of tigecycline-bound human mitochondrial 55S, 39S, cytoplasmic 80S and yeast cytoplasmic 80S ribosomes. We find that at clinically relevant concentrations, tigecycline effectively targets human 55S mitoribosomes, potentially, by hindering A-site tRNA accommodation and by blocking the peptidyl transfer center. In contrast, tigecycline does not bind to human 80S ribosomes under physiological concentrations. However, at high tigecycline concentrations, in addition to blocking the A-site, both human and yeast 80S ribosomes bind tigecycline at another conserved binding site restricting the movement of the L1 stalk. In conclusion, the observed distinct binding properties of tigecycline may guide new pathways for drug design and therapy.

Structural basis for differential inhibition of eukaryotic ribosomes by tigecycline.,Li X, Wang M, Denk T, Buschauer R, Li Y, Beckmann R, Cheng J Nat Commun. 2024 Jun 28;15(1):5481. doi: 10.1038/s41467-024-49797-7. PMID:38942792<ref>PMID:38942792</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 8xt1" style="background-color:#fffaf0;"></div>
== References ==
<references/>
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Cheng J]]
[[Category: Li X]]
[[Category: Wang M]]