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[[Image:1knc.gif|left|200px]]


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==Structure of AhpD from Mycobacterium tuberculosis, a novel enzyme with thioredoxin-like activity.==
The line below this paragraph, containing "STRUCTURE_1knc", creates the "Structure Box" on the page.
<StructureSection load='1knc' size='340' side='right'caption='[[1knc]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
You may change the PDB parameter (which sets the PDB file loaded into the applet)
== Structural highlights ==
or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
<table><tr><td colspan='2'>[[1knc]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Mycobacterium_tuberculosis Mycobacterium tuberculosis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1KNC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1KNC FirstGlance]. <br>
or leave the SCENE parameter empty for the default display.
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2&#8491;</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
{{STRUCTURE_1knc|  PDB=1knc  |  SCENE= }}
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1knc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1knc OCA], [https://pdbe.org/1knc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1knc RCSB], [https://www.ebi.ac.uk/pdbsum/1knc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1knc ProSAT]</span></td></tr>
 
</table>
'''Structure of AhpD from Mycobacterium tuberculosis, a novel enzyme with thioredoxin-like activity.'''
== Function ==
 
[https://www.uniprot.org/uniprot/AHPD_MYCTU AHPD_MYCTU] Antioxidant protein with alkyl hydroperoxidase activity. Required for the reduction of the AhpC active site cysteine residues and for the regeneration of the AhpC enzyme activity.<ref>PMID:10766746</ref> <ref>PMID:11799204</ref> <ref>PMID:12761216</ref>  Together with AhpC, DlaT and Lpd, constitutes an NADH-dependent peroxidase active against hydrogen and alkyl peroxides as well as serving as a peroxynitrite reductase, thus protecting the bacterium against reactive nitrogen intermediates and oxidative stress generated by the host immune system.<ref>PMID:10766746</ref> <ref>PMID:11799204</ref> <ref>PMID:12761216</ref>
 
== Evolutionary Conservation ==
==Overview==
[[Image:Consurf_key_small.gif|200px|right]]
Mycobacterium tuberculosis (Mtb) mounts a stubborn defense against oxidative and nitrosative components of the immune response. Dihydrolipoamide dehydrogenase (Lpd) and dihydrolipoamide succinyltransferase (SucB) are components of alpha-ketoacid dehydrogenase complexes that are central to intermediary metabolism. We find that Lpd and SucB support Mtb's antioxidant defense. The peroxiredoxin alkyl hydroperoxide reductase (AhpC) is linked to Lpd and SucB by an adaptor protein, AhpD. The 2.0 angstrom AhpD crystal structure reveals a thioredoxin-like active site that is responsive to lipoamide. We propose that Lpd, SucB (the only lipoyl protein detected in Mtb), AhpD, and AhpC together constitute a nicotinamide adenine dinucleotide (reduced)-dependent peroxidase and peroxynitrite reductase. AhpD thus represents a class of thioredoxin-like molecules that enables an antioxidant defense.
Check<jmol>
 
  <jmolCheckbox>
==About this Structure==
    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/kn/1knc_consurf.spt"</scriptWhenChecked>
1KNC is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Mycobacterium_tuberculosis Mycobacterium tuberculosis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1KNC OCA].  
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
 
    <text>to colour the structure by Evolutionary Conservation</text>
==Reference==
  </jmolCheckbox>
Metabolic enzymes of mycobacteria linked to antioxidant defense by a thioredoxin-like protein., Bryk R, Lima CD, Erdjument-Bromage H, Tempst P, Nathan C, Science. 2002 Feb 8;295(5557):1073-7. Epub 2002 Jan 17. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/11799204 11799204]
</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=1knc ConSurf].
<div style="clear:both"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Mycobacterium tuberculosis]]
[[Category: Mycobacterium tuberculosis]]
[[Category: Single protein]]
[[Category: Bryk R]]
[[Category: Bryk, R.]]
[[Category: Erdjument-Bromage H]]
[[Category: Erdjument-Bromage, H.]]
[[Category: Lima CD]]
[[Category: Lima, C D.]]
[[Category: Nathan C]]
[[Category: Nathan, C.]]
[[Category: Tempst P]]
[[Category: Tempst, P.]]
[[Category: Ahpd]]
[[Category: Disulfide]]
[[Category: Lpd]]
[[Category: Peroxiredoxin]]
[[Category: Redox]]
[[Category: Thioredoxin]]
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May  2 22:56:40 2008''

Latest revision as of 10:26, 14 February 2024

Structure of AhpD from Mycobacterium tuberculosis, a novel enzyme with thioredoxin-like activity.Structure of AhpD from Mycobacterium tuberculosis, a novel enzyme with thioredoxin-like activity.

Structural highlights

1knc is a 3 chain structure with sequence from Mycobacterium tuberculosis. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 2Å
Ligands:
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

AHPD_MYCTU Antioxidant protein with alkyl hydroperoxidase activity. Required for the reduction of the AhpC active site cysteine residues and for the regeneration of the AhpC enzyme activity.[1] [2] [3] Together with AhpC, DlaT and Lpd, constitutes an NADH-dependent peroxidase active against hydrogen and alkyl peroxides as well as serving as a peroxynitrite reductase, thus protecting the bacterium against reactive nitrogen intermediates and oxidative stress generated by the host immune system.[4] [5] [6]

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

References

  1. ↑ Hillas PJ, del Alba FS, Oyarzabal J, Wilks A, Ortiz De Montellano PR. The AhpC and AhpD antioxidant defense system of Mycobacterium tuberculosis. J Biol Chem. 2000 Jun 23;275(25):18801-9. PMID:10766746 doi:http://dx.doi.org/10.1074/jbc.M001001200
  2. ↑ Bryk R, Lima CD, Erdjument-Bromage H, Tempst P, Nathan C. Metabolic enzymes of mycobacteria linked to antioxidant defense by a thioredoxin-like protein. Science. 2002 Feb 8;295(5557):1073-7. Epub 2002 Jan 17. PMID:11799204 doi:10.1126/science.1067798
  3. ↑ Koshkin A, Nunn CM, Djordjevic S, Ortiz de Montellano PR. The mechanism of Mycobacterium tuberculosis alkylhydroperoxidase AhpD as defined by mutagenesis, crystallography, and kinetics. J Biol Chem. 2003 Aug 8;278(32):29502-8. Epub 2003 May 21. PMID:12761216 doi:10.1074/jbc.M303747200
  4. ↑ Hillas PJ, del Alba FS, Oyarzabal J, Wilks A, Ortiz De Montellano PR. The AhpC and AhpD antioxidant defense system of Mycobacterium tuberculosis. J Biol Chem. 2000 Jun 23;275(25):18801-9. PMID:10766746 doi:http://dx.doi.org/10.1074/jbc.M001001200
  5. ↑ Bryk R, Lima CD, Erdjument-Bromage H, Tempst P, Nathan C. Metabolic enzymes of mycobacteria linked to antioxidant defense by a thioredoxin-like protein. Science. 2002 Feb 8;295(5557):1073-7. Epub 2002 Jan 17. PMID:11799204 doi:10.1126/science.1067798
  6. ↑ Koshkin A, Nunn CM, Djordjevic S, Ortiz de Montellano PR. The mechanism of Mycobacterium tuberculosis alkylhydroperoxidase AhpD as defined by mutagenesis, crystallography, and kinetics. J Biol Chem. 2003 Aug 8;278(32):29502-8. Epub 2003 May 21. PMID:12761216 doi:10.1074/jbc.M303747200

1knc, resolution 2.00Å

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