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| - | | + | #REDIRECT [[5syi]] This PDB entry is obsolete and replaced by 5syi |
| - | ==Structure of D141A variant of B. pseudomallei KatG complexed with INH==
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| - | <StructureSection load='4ka6' size='340' side='right' caption='[[4ka6]], [[Resolution|resolution]] 1.70Å' scene=''>
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| - | == Structural highlights ==
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| - | <table><tr><td colspan='2'>[[4ka6]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Burps Burps]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4KA6 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4KA6 FirstGlance]. <br>
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| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene>, <scene name='pdbligand=MPD:(4S)-2-METHYL-2,4-PENTANEDIOL'>MPD</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=NIZ:PYRIDINE-4-CARBOHYDRAZIDE'>NIZ</scene></td></tr>
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| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4ka5|4ka5]]</td></tr>
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| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">BPSL2865, katG ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=272560 BURPS])</td></tr>
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| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Catalase_peroxidase Catalase peroxidase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.11.1.21 1.11.1.21] </span></td></tr>
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| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4ka6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ka6 OCA], [http://pdbe.org/4ka6 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4ka6 RCSB], [http://www.ebi.ac.uk/pdbsum/4ka6 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4ka6 ProSAT]</span></td></tr>
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| - | </table>
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| - | == Function ==
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| - | [[http://www.uniprot.org/uniprot/KATG_BURPS KATG_BURPS]] Bifunctional enzyme with both catalase and broad-spectrum peroxidase activity. Displays also NADH oxidase, isoniazid hydrazine lyase and isonicotinoyl-NAD synthase activity.<ref>PMID:15280362</ref>
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| - | <div style="background-color:#fffaf0;">
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| - | == Publication Abstract from PubMed ==
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| - | Isonicotinic acid hydrazide (isoniazid or INH) is a front line antitubercular pro-drug that is converted to its active form, isonicotinyl-NAD, by the bacterial catalase-peroxidase KatG. Understanding the role of KatG in the INH activation process has been hampered by a lack of knowledge of the actual drug binding site. In this work, we have investigated the binding of INH in the main access channel of KatG with a combination of molecular dynamics, using an enhanced-sampling technique (metadynamics), X-ray crystallography, and site-directed mutagenesis. The metadynamics simulations show that there are several weak drug binding sites along the access channel. Moreover, the simulations evidence that complete entrance to the heme active site is impeded by an aspartate residue (D141) located above the heme. This has been confirmed by structural and functional analysis of the D141A mutant, leading to the first X-ray crystallography evidence of INH at the heme access channel.
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| - | Binding of the Antitubercular Pro-Drug Isoniazid in the Heme Access Channel of Catalase-Peroxidase (KatG). A Combined Structural and Metadynamics Investigation.,Vidossich P, Loewen PC, Carpena X, Fiorin G, Fita I, Rovira C J Phys Chem B. 2014 Mar 20;118(11):2924-31. doi: 10.1021/jp4123425. Epub 2014 Mar, 7. PMID:24568093<ref>PMID:24568093</ref>
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| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
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| - | </div>
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| - | <div class="pdbe-citations 4ka6" style="background-color:#fffaf0;"></div>
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| - | == References ==
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| - | <references/>
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| - | __TOC__
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| - | </StructureSection>
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| - | [[Category: Burps]]
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| - | [[Category: Catalase peroxidase]]
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| - | [[Category: Loewen, P C]]
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| - | [[Category: Catalase-peroxidase]]
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| - | [[Category: D141a variant]]
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| - | [[Category: Isoniazid]]
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| - | [[Category: Katg]]
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| - | [[Category: Oxidoreductase]]
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