View source for 7u22


==Mycobacterium tuberculosis RNA polymerase sigma A holoenzyme open promoter complex containing UMN-7==
<StructureSection load='7u22' size='340' side='right'caption='[[7u22]], [[Resolution|resolution]] 3.87&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7u22]] is a 8 chain structure with sequence from [https://en.wikipedia.org/wiki/Mycobacterium_tuberculosis Mycobacterium tuberculosis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7U22 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7U22 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]] 3.87&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=KYO:(9S,14S,15R,16S,17R,18R,19R,20S,21S,25R)-5,6,18,20-tetrahydroxy-14-methoxy-7,9,15,17,19,21,25-heptamethyl-1-(2-methylpropyl)-10,26-dioxo-1,3,9,10-tetrahydrospiro[9,4-(epoxypentadecanoimino)furo[2,3 7,8]naphtho[1,2-d]imidazole-2,4-piperidin]-16-yl+benzoate'>KYO</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</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=7u22 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7u22 OCA], [https://pdbe.org/7u22 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7u22 RCSB], [https://www.ebi.ac.uk/pdbsum/7u22 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7u22 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/RPOA_MYCTA RPOA_MYCTA] DNA-dependent RNA polymerase catalyzes the transcription of DNA into RNA using the four ribonucleoside triphosphates as substrates.
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Rifamycin antibiotics are a valuable class of antimicrobials for treating infections by mycobacteria and other persistent bacteria owing to their potent bactericidal activity against replicating and non-replicating pathogens. However, the clinical utility of rifamycins against Mycobacterium abscessus is seriously compromised by a novel resistance mechanism, namely, rifamycin inactivation by ADP-ribosylation. Using a structure-based approach, we rationally redesign rifamycins through strategic modification of the ansa-chain to block ADP-ribosylation while preserving on-target activity. Validated by a combination of biochemical, structural, and microbiological studies, the most potent analogs overcome ADP-ribosylation, restored their intrinsic low nanomolar activity and demonstrated significant in vivo antibacterial efficacy. Further optimization by tuning drug disposition properties afforded a preclinical candidate with remarkable potency and an outstanding pharmacokinetic profile.

Redesign of Rifamycin Antibiotics to Overcome ADP-Ribosylation-Mediated Resistance.,Lan T, Ganapathy US, Sharma S, Ahn YM, Zimmerman M, Molodtsov V, Hegde P, Gengenbacher M, Ebright RH, Dartois V, Freundlich JS, Dick T, Aldrich CC Angew Chem Int Ed Engl. 2022 Oct 12:e202211498. doi: 10.1002/anie.202211498. PMID:36222275<ref>PMID:36222275</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 7u22" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Mycobacterium tuberculosis]]
[[Category: Ebright RH]]
[[Category: Molodtsov V]]