|
|
| Line 3: |
Line 3: |
| | <StructureSection load='7a7a' size='340' side='right'caption='[[7a7a]], [[Resolution|resolution]] 3.08Å' scene=''> | | <StructureSection load='7a7a' size='340' side='right'caption='[[7a7a]], [[Resolution|resolution]] 3.08Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[7a7a]] 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=7A7A OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7A7A FirstGlance]. <br> | + | <table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7A7A OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7A7A FirstGlance]. <br> |
| - | </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> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 3.08Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">katG, 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='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='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=7a7a FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7a7a OCA], [https://pdbe.org/7a7a PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7a7a RCSB], [https://www.ebi.ac.uk/pdbsum/7a7a PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7a7a ProSAT]</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=7a7a FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7a7a OCA], [https://pdbe.org/7a7a PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7a7a RCSB], [https://www.ebi.ac.uk/pdbsum/7a7a PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7a7a 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;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
| Line 27: |
Line 24: |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Catalase peroxidase]] | |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Blundell, T L]] | + | [[Category: Blundell TL]] |
| - | [[Category: Chaplin, A K]] | + | [[Category: Chaplin AK]] |
| - | [[Category: Munir, A]] | + | [[Category: Munir A]] |
| - | [[Category: Heme]]
| + | |
| - | [[Category: Metal binding protein]]
| + | |
| - | [[Category: Peroxidase-catalase]]
| + | |
| Structural highlights
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[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Munir A, Wilson MT, Hardwick SW, Chirgadze DY, Worrall JAR, Blundell TL, Chaplin AK. Using cryo-EM to understand antimycobacterial resistance in the catalase-peroxidase (KatG) from Mycobacterium tuberculosis. Structure. 2021 Jan 4. pii: S0969-2126(20)30475-5. doi:, 10.1016/j.str.2020.12.008. PMID:33444527 doi:http://dx.doi.org/10.1016/j.str.2020.12.008
|
