View source for 7kgb


==CryoEM structure of A2296-methylated Mycobacterium tuberculosis ribosome bound with SEQ-9==
<StructureSection load='7kgb' size='340' side='right'caption='[[7kgb]], [[Resolution|resolution]] 2.70&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7kgb]] is a 10 chain structure with sequence from [https://en.wikipedia.org/wiki/Mycobacterium_tuberculosis_H37Rv Mycobacterium tuberculosis H37Rv]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7KGB OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7KGB 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]] 2.7&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=2MG:2N-METHYLGUANOSINE-5-MONOPHOSPHATE'>2MG</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=G7M:N7-METHYL-GUANOSINE-5-MONOPHOSPHATE'>G7M</scene>, <scene name='pdbligand=MA6:6N-DIMETHYLADENOSINE-5-MONOPHOSHATE'>MA6</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=OMC:O2-METHYLYCYTIDINE-5-MONOPHOSPHATE'>OMC</scene>, <scene name='pdbligand=OMG:O2-METHYLGUANOSINE-5-MONOPHOSPHATE'>OMG</scene>, <scene name='pdbligand=UR3:3-METHYLURIDINE-5-MONOPHOSHATE'>UR3</scene>, <scene name='pdbligand=WDP:Sequanamycin+9'>WDP</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=7kgb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7kgb OCA], [https://pdbe.org/7kgb PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7kgb RCSB], [https://www.ebi.ac.uk/pdbsum/7kgb PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7kgb ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/RL32_MYCTU RL32_MYCTU] 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The emergence of drug-resistant tuberculosis has created an urgent need for new anti-tubercular agents. Here, we report the discovery of a series of macrolides called sequanamycins with outstanding in vitro and in vivo activity against Mycobacterium tuberculosis (Mtb). Sequanamycins are bacterial ribosome inhibitors that interact with the ribosome in a similar manner to classic macrolides like erythromycin and clarithromycin, but with binding characteristics that allow them to overcome the inherent macrolide resistance of Mtb. Structures of the ribosome with bound inhibitors were used to optimize sequanamycin to produce the advanced lead compound SEQ-9. SEQ-9 was efficacious in mouse models of acute and chronic TB as a single agent, and it demonstrated bactericidal activity in a murine TB infection model in combination with other TB drugs. These results support further investigation of this series as TB clinical candidates, with the potential for use in new regimens against drug-susceptible and drug-resistant TB.

Discovery of natural-product-derived sequanamycins as potent oral anti-tuberculosis agents.,Zhang J, Lair C, Roubert C, Amaning K, Barrio MB, Benedetti Y, Cui Z, Xing Z, Li X, Franzblau SG, Baurin N, Bordon-Pallier F, Cantalloube C, Sans S, Silve S, Blanc I, Fraisse L, Rak A, Jenner LB, Yusupova G, Yusupov M, Zhang J, Kaneko T, Yang TJ, Fotouhi N, Nuermberger E, Tyagi S, Betoudji F, Upton A, Sacchettini JC, Lagrange S Cell. 2023 Mar 2;186(5):1013-1025.e24. doi: 10.1016/j.cell.2023.01.043. Epub 2023 , Feb 23. PMID:36827973<ref>PMID:36827973</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 7kgb" style="background-color:#fffaf0;"></div>

==See Also==
*[[Ribosome 3D structures|Ribosome 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Mycobacterium tuberculosis H37Rv]]
[[Category: Cui Z]]
[[Category: Zhang J]]