7a8z: Difference between revisions
New page: '''Unreleased structure''' The entry 7a8z is ON HOLD Authors: Blundell, T.L., Chaplin, A.K., Munir, A. Description: Cryo-EM structure of T275P KatG from M. tuberculosis [[Category: Unr... |
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The | ==Cryo-EM structure of T275P KatG from M. tuberculosis== | ||
<StructureSection load='7a8z' size='340' side='right'caption='[[7a8z]], [[Resolution|resolution]] 3.35Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7A8Z OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7A8Z 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]] 3.35Å</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=7a8z FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7a8z OCA], [https://pdbe.org/7a8z PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7a8z RCSB], [https://www.ebi.ac.uk/pdbsum/7a8z PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7a8z ProSAT]</span></td></tr> | |||
</table> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Resolution advances in cryoelectron microscopy (cryo-EM) now offer the possibility to visualize structural effects of naturally occurring resistance mutations in proteins and also of understanding the binding mechanisms of small drug molecules. In Mycobacterium tuberculosis the multifunctional heme enzyme KatG is indispensable for activation of isoniazid (INH), a first-line pro-drug for treatment of tuberculosis. We present a cryo-EM methodology for structural and functional characterization of KatG and INH resistance variants. The cryo-EM structure of the 161 kDa KatG dimer in the presence of INH is reported to 2.7 A resolution allowing the observation of potential INH binding sites. In addition, cryo-EM structures of two INH resistance variants, identified from clinical isolates, W107R and T275P, are reported. In combination with electronic absorbance spectroscopy our cryo-EM approach reveals how these resistance variants cause disorder in the heme environment preventing heme uptake and retention, providing insight into INH resistance. | |||
Using cryo-EM to understand antimycobacterial resistance in the catalase-peroxidase (KatG) from Mycobacterium tuberculosis.,Munir A, Wilson MT, Hardwick SW, Chirgadze DY, Worrall JAR, Blundell TL, Chaplin AK Structure. 2021 Jan 4. pii: S0969-2126(20)30475-5. doi:, 10.1016/j.str.2020.12.008. PMID:33444527<ref>PMID:33444527</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: Blundell | <div class="pdbe-citations 7a8z" style="background-color:#fffaf0;"></div> | ||
[[Category: Chaplin | |||
[[Category: Munir | ==See Also== | ||
*[[Catalase 3D structures|Catalase 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Large Structures]] | |||
[[Category: Blundell TL]] | |||
[[Category: Chaplin AK]] | |||
[[Category: Munir A]] | |||
Latest revision as of 11:53, 14 July 2024
Cryo-EM structure of T275P KatG from M. tuberculosisCryo-EM structure of T275P KatG from M. tuberculosis
Structural highlights
Publication Abstract from PubMedResolution advances in cryoelectron microscopy (cryo-EM) now offer the possibility to visualize structural effects of naturally occurring resistance mutations in proteins and also of understanding the binding mechanisms of small drug molecules. In Mycobacterium tuberculosis the multifunctional heme enzyme KatG is indispensable for activation of isoniazid (INH), a first-line pro-drug for treatment of tuberculosis. We present a cryo-EM methodology for structural and functional characterization of KatG and INH resistance variants. The cryo-EM structure of the 161 kDa KatG dimer in the presence of INH is reported to 2.7 A resolution allowing the observation of potential INH binding sites. In addition, cryo-EM structures of two INH resistance variants, identified from clinical isolates, W107R and T275P, are reported. In combination with electronic absorbance spectroscopy our cryo-EM approach reveals how these resistance variants cause disorder in the heme environment preventing heme uptake and retention, providing insight into INH resistance. Using cryo-EM to understand antimycobacterial resistance in the catalase-peroxidase (KatG) from Mycobacterium tuberculosis.,Munir A, Wilson MT, Hardwick SW, Chirgadze DY, Worrall JAR, Blundell TL, Chaplin AK Structure. 2021 Jan 4. pii: S0969-2126(20)30475-5. doi:, 10.1016/j.str.2020.12.008. PMID:33444527[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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