View source for 2vcs


==Structure of isoniazid (INH) bound to cytosolic soybean ascorbate peroxidase mutant H42A==
<StructureSection load='2vcs' size='340' side='right'caption='[[2vcs]], [[Resolution|resolution]] 1.68&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[2vcs]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Glycine_max Glycine max]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2VCS OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2VCS 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]] 1.68&#8491;</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>, <scene name='pdbligand=ISZ:4-(DIAZENYLCARBONYL)PYRIDINE'>ISZ</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=2vcs FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2vcs OCA], [https://pdbe.org/2vcs PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2vcs RCSB], [https://www.ebi.ac.uk/pdbsum/2vcs PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2vcs ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/Q43758_SOYBN Q43758_SOYBN] 
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
  <jmolCheckbox>
    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/vc/2vcs_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
    <text>to colour the structure by Evolutionary Conservation</text>
  </jmolCheckbox>
</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=2vcs ConSurf].
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== Publication Abstract from PubMed ==
Isoniazid (INH, isonicotinic acid hydrazine) is one of only two therapeutic agents effective in treating tuberculosis. This prodrug is activated by the heme enzyme catalase peroxidase (KatG) endogenous to Mycobacterium tuberculosis but the mechanism of activation is poorly understood, in part because the binding interaction has not been properly established. The class I peroxidases ascorbate peroxidase (APX) and cytochrome c peroxidase (CcP) have active site structures very similar to KatG and are also capable of activating isoniazid. We report here the first crystal structures of complexes of isoniazid bound to APX and CcP. These are the first structures of isoniazid bound to any activating enzymes. The structures show that isoniazid binds close to the delta-heme edge in both APX and CcP, although the precise binding orientation varies slightly in the two cases. A second binding site for INH is found in APX at the gamma-heme edge close to the established ascorbate binding site, indicating that the gamma-heme edge can also support the binding of aromatic substrates. We also show that in an active site mutant of soybean APX (W41A) INH can bind directly to the heme iron to become an inhibitor and in a different mode when the distal histidine is replaced by alanine (H42A). These structures provide the first unambiguous evidence for the location of the isoniazid binding site in the class I peroxidases and provide rationalization of isoniazid resistance in naturally occurring KatG mutant strains of M. tuberculosis.

The tuberculosis prodrug isoniazid bound to activating peroxidases.,Metcalfe C, Macdonald IK, Murphy EJ, Brown KA, Raven EL, Moody PC J Biol Chem. 2008 Mar 7;283(10):6193-200. Epub 2007 Dec 5. PMID:18056997<ref>PMID:18056997</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 2vcs" style="background-color:#fffaf0;"></div>

==See Also==
*[[Ascorbate peroxidase 3D structures|Ascorbate peroxidase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Glycine max]]
[[Category: Large Structures]]
[[Category: Brown KA]]
[[Category: Macdonald IK]]
[[Category: Metcalfe CL]]
[[Category: Moody PCE]]
[[Category: Raven EL]]