View source for 5sxx


==Crystal structure of the E198A variant of Burkholderia pseudomallei catalase-peroxidase KatG with INH==
<StructureSection load='5sxx' size='340' side='right'caption='[[5sxx]], [[Resolution|resolution]] 1.70&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5sxx]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Burkholderia_pseudomallei_1710b Burkholderia pseudomallei 1710b]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5SXX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5SXX FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.7&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><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=OXY:OXYGEN+MOLECULE'>OXY</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene></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=5sxx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5sxx OCA], [https://pdbe.org/5sxx PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5sxx RCSB], [https://www.ebi.ac.uk/pdbsum/5sxx PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5sxx ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/KATG_BURP1 KATG_BURP1] Bifunctional enzyme with both catalase and broad-spectrum peroxidase activity.
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
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 &gt;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.

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>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 5sxx" style="background-color:#fffaf0;"></div>

==See Also==
*[[Catalase 3D structures|Catalase 3D structures]]
== References ==
<references/>
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</StructureSection>
[[Category: Burkholderia pseudomallei 1710b]]
[[Category: Large Structures]]
[[Category: Loewen PC]]