View source for 7aa3


==T275P after heme uptake from M. tuberculosis==
<StructureSection load='7aa3' size='340' side='right'caption='[[7aa3]], [[Resolution|resolution]] 3.56&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7AA3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7AA3 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]] 3.56&#8491;</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=7aa3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7aa3 OCA], [https://pdbe.org/7aa3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7aa3 RCSB], [https://www.ebi.ac.uk/pdbsum/7aa3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7aa3 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&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 7aa3" style="background-color:#fffaf0;"></div>

==See Also==
*[[Catalase 3D structures|Catalase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Blundell TL]]
[[Category: Chaplin AK]]
[[Category: Munir A]]