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| - | | + | #REDIRECT [[5sxx]] This PDB entry is obsolete and replaced by 5sxx |
| - | ==Crystal structure of the E198A variant of Burkholderia pseudomallei catalase-peroxidase KatG with INH==
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| - | <StructureSection load='3n3s' size='340' side='right' caption='[[3n3s]], [[Resolution|resolution]] 1.70Å' scene=''>
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| - | == Structural highlights ==
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| - | <table><tr><td colspan='2'>[[3n3s]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/"bacillus_pseudomallei"_whitmore_1913 "bacillus pseudomallei" whitmore 1913]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3N3S OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3N3S 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=MRD:(4R)-2-METHYLPENTANE-2,4-DIOL'>MRD</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene></td></tr>
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| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3n3n|3n3n]], [[3n3o|3n3o]], [[3n3p|3n3p]], [[3n3q|3n3q]], [[3n3r|3n3r]]</td></tr>
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| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">KatG ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=28450 "Bacillus pseudomallei" Whitmore 1913])</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 Catalase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.11.1.6 1.11.1.6] </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=3n3s FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3n3s OCA], [http://pdbe.org/3n3s PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3n3s RCSB], [http://www.ebi.ac.uk/pdbsum/3n3s PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3n3s ProSAT]</span></td></tr>
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| - | </table>
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| - | == Function ==
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| - | [[http://www.uniprot.org/uniprot/C6TXM5_BURPE C6TXM5_BURPE]] Bifunctional enzyme with both catalase and broad-spectrum peroxidase activity (By similarity).[HAMAP-Rule:MF_01961]
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| - | == Evolutionary Conservation ==
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| - | [[Image:Consurf_key_small.gif|200px|right]]
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| - | Check<jmol>
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| - | <jmolCheckbox>
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| - | <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/n3/3n3s_consurf.spt"</scriptWhenChecked>
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| - | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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| - | <text>to colour the structure by Evolutionary Conservation</text>
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| - | </jmolCheckbox>
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| - | </jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=3n3s ConSurf].
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| - | <div style="clear:both"></div>
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| - | <div style="background-color:#fffaf0;">
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| - | == Publication Abstract from PubMed ==
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| - | Activation of the pro-drug isoniazid (INH) as an anti-tubercular drug in Mycobacterium tuberculosis involves its conversion to isonicotinyl-NAD, a reaction that requires the catalase-peroxidase KatG. This report shows that the reaction proceeds in the absence of KatG at a slow rate in a mixture of INH, NAD(+), Mn(2+), and O(2), and that the inclusion of KatG increases the rate by >7 times. Superoxide, generated by either Mn(2+)- or KatG-catalyzed reduction of O(2), is an essential intermediate in the reaction. Elimination of the peroxidatic process by mutation slows the rate of reaction by 60% revealing that the peroxidatic process enhances, but is not essential for isonicotinyl-NAD formation. The isonicotinyl-NAD(*+) radical is identified as a reaction intermediate, and its reduction by superoxide is proposed. Binding sites for INH and its co-substrate, NAD(+), are identified for the first time in crystal complexes of Burkholderia pseudomallei catalase-peroxidase with INH and NAD(+) grown by co-crystallization. The best defined INH binding sites were identified, one in each subunit, on the opposite side of the protein from the entrance to the heme cavity in a funnel-shaped channel. The NAD(+) binding site is approximately 20 A from the entrance to the heme cavity and involves interactions primarily with the AMP portion of the molecule in agreement with the NMR saturation transfer difference results.
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| - | Isonicotinic acid hydrazide conversion to Isonicotinyl-NAD by catalase-peroxidases.,Wiseman B, Carpena X, Feliz M, Donald LJ, Pons M, Fita I, Loewen PC J Biol Chem. 2010 Aug 20;285(34):26662-73. Epub 2010 Jun 15. PMID:20554537<ref>PMID:20554537</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 3n3s" style="background-color:#fffaf0;"></div>
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| - | ==See Also==
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| - | *[[Catalase|Catalase]]
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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: Bacillus pseudomallei whitmore 1913]]
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| - | [[Category: Catalase]]
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| - | [[Category: Carpena, X]]
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| - | [[Category: Fita, I]]
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| - | [[Category: Loewen, P C]]
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| - | [[Category: Wiseman, B]]
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| - | [[Category: Catalase-peroxidase]]
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| - | [[Category: Isoniazid]]
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| - | [[Category: Oxidoreductase]]
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| - | [[Category: Pro-drug activation]]
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| - | [[Category: Tuberculosis]]
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