7ag8: Difference between revisions
Jump to navigation
Jump to search
No edit summary |
No edit summary |
||
| Line 1: | Line 1: | ||
==Cryo-EM structure of wild-type KatG from M. tuberculosis== | ==Cryo-EM structure of wild-type KatG from M. tuberculosis== | ||
<StructureSection load='7ag8' size='340' side='right'caption='[[7ag8]]' scene=''> | <StructureSection load='7ag8' size='340' side='right'caption='[[7ag8]], [[Resolution|resolution]] 2.68Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7AG8 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7AG8 FirstGlance]. <br> | <table><tr><td colspan='2'>[[7ag8]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/"bacillus_tuberculosis"_(zopf_1883)_klein_1884 "bacillus tuberculosis" (zopf 1883) klein 1884]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7AG8 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7AG8 FirstGlance]. <br> | ||
</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=7ag8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7ag8 OCA], [https://pdbe.org/7ag8 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7ag8 RCSB], [https://www.ebi.ac.uk/pdbsum/7ag8 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7ag8 ProSAT]</span></td></tr> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene></td></tr> | ||
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">katG, AYJ03_010035, ERS007661_00994, ERS013471_02729, ERS024276_01596, ERS075361_01376, ERS094182_01139, F6W99_00474, FRD82_12135 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1773 "Bacillus tuberculosis" (Zopf 1883) Klein 1884])</td></tr> | |||
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Catalase_peroxidase Catalase peroxidase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.11.1.21 1.11.1.21] </span></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=7ag8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7ag8 OCA], [https://pdbe.org/7ag8 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7ag8 RCSB], [https://www.ebi.ac.uk/pdbsum/7ag8 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7ag8 ProSAT]</span></td></tr> | |||
</table> | </table> | ||
== Function == | |||
[[https://www.uniprot.org/uniprot/A0A0D5ZBI4_MYCTX A0A0D5ZBI4_MYCTX]] Bifunctional enzyme with both catalase and broad-spectrum peroxidase activity.[HAMAP-Rule:MF_01961] | |||
<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> | |||
</div> | |||
<div class="pdbe-citations 7ag8" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Catalase 3D structures|Catalase 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Catalase peroxidase]] | |||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Blundell | [[Category: Blundell, T L]] | ||
[[Category: Chaplin | [[Category: Chaplin, A K]] | ||
[[Category: Munir A]] | [[Category: Munir, A]] | ||
[[Category: Heme]] | |||
[[Category: Metal binding protein]] | |||
[[Category: Peroxidase-catalase]] | |||
Revision as of 09:15, 18 August 2021
Cryo-EM structure of wild-type KatG from M. tuberculosisCryo-EM structure of wild-type KatG from M. tuberculosis
Structural highlights
Function[A0A0D5ZBI4_MYCTX] Bifunctional enzyme with both catalase and broad-spectrum peroxidase activity.[HAMAP-Rule:MF_01961] 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
|
| ||||||||||||||||||||