View source for 7azo


==70S thermus thermophilus ribosome with bound antibiotic lead SEQ-977==
<StructureSection load='7azo' size='340' side='right'caption='[[7azo]], [[Resolution|resolution]] 3.30&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7azo]] is a 20 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli] and [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=7AZO OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7AZO 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]] 3.3&#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=3AU:3-[(3S)-3-AMINO-3-CARBOXYPROPYL]URIDINE+5-(DIHYDROGEN+PHOSPHATE)'>3AU</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=G7M:N7-METHYL-GUANOSINE-5-MONOPHOSPHATE'>G7M</scene>, <scene name='pdbligand=H2U:5,6-DIHYDROURIDINE-5-MONOPHOSPHATE'>H2U</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=OHX:OSMIUM+(III)+HEXAMMINE'>OHX</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=SJE:[(2~{R},3~{S},4~{R},5~{R},7~{S},9~{S},10~{S},11~{R},12~{S},13~{R})-2-[(2~{S})-1-[(2~{R},3~{R},4~{R},5~{R},6~{R})-3,4-dimethoxy-6-methyl-5-oxidanyl-oxan-2-yl]oxypropan-2-yl]-12-[(2~{R},4~{R},5~{S},6~{S})-4,6-dimethyl-4,5-bis(oxidanyl)oxan-2-yl]oxy-10-[(2~{S},3~{R},4~{R},6~{R})-4-(methoxyamino)-6-methyl-3-oxidanyl-oxan-2-yl]oxy-3,5,7,9,11,13-hexamethyl-7-[2-[(2-nitrophenyl)sulfonylamino]ethylcarbamoyloxy]-6,14-bis(oxidanylidene)-1-oxacyclotetradec-4-yl]+3-methylbutanoate'>SJE</scene>, <scene name='pdbligand=UR3:3-METHYLURIDINE-5-MONOPHOSHATE'>UR3</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=7azo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7azo OCA], [https://pdbe.org/7azo PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7azo RCSB], [https://www.ebi.ac.uk/pdbsum/7azo PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7azo ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/RS4_THET8 RS4_THET8] One of the primary rRNA binding proteins, it binds directly to 16S rRNA where it helps nucleate assembly of the body and platform of the 30S subunit. Binds mRNA in the 70S ribosome, positioning it for translation.[HAMAP-Rule:MF_01306_B]
<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 7azo" style="background-color:#fffaf0;"></div>

==See Also==
*[[Ribosomal protein THX 3D structures|Ribosomal protein THX 3D structures]]
*[[Ribosome 3D structures|Ribosome 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Escherichia coli]]
[[Category: Large Structures]]
[[Category: Thermus thermophilus HB8]]
[[Category: Jenner LB]]
[[Category: Yusupov M]]
[[Category: Yusupova G]]