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- | [[Image:1me5.jpg|left|200px]] | |
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- | <!--
| + | ==Crystal Structure of Mycobacterium Tuberculosis Alkylperoxidase AhpD H132Q Mutant== |
- | The line below this paragraph, containing "STRUCTURE_1me5", creates the "Structure Box" on the page.
| + | <StructureSection load='1me5' size='340' side='right'caption='[[1me5]], [[Resolution|resolution]] 2.40Å' 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'>[[1me5]] 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=1ME5 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1ME5 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]] 2.4Å</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=1me5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1me5 OCA], [https://pdbe.org/1me5 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1me5 RCSB], [https://www.ebi.ac.uk/pdbsum/1me5 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1me5 ProSAT]</span></td></tr> |
- | {{STRUCTURE_1me5| PDB=1me5 | SCENE= }}
| + | </table> |
- | | + | == Function == |
- | '''Crystal Structure of Mycobacterium Tuberculosis Alkylperoxidase AhpD H132Q Mutant'''
| + | [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 == |
- | | + | [[Image:Consurf_key_small.gif|200px|right]] |
- | ==Overview== | + | Check<jmol> |
- | AhpD, a protein with two cysteine residues, is required for physiological reduction of the Mycobacterium tuberculosis alkylhydroperoxidase AhpC. AhpD also has an alkylhydroperoxidase activity of its own. The AhpC/AhpD system provides critical antioxidant protection, particularly in the absence of the catalase-peroxidase KatG, which is suppressed in most isoniazid-resistant strains. Based on the crystal structure, we proposed recently a catalytic mechanism for AhpD involving a proton relay in which the Glu118 carboxylate group, via His137 and a water molecule, deprotonates the catalytic residue Cys133 (Nunn, C. M., Djordjevic, S., Hillas, P. J., Nishida, C., and Ortiz de Montellano, P. R. (2002) J. Biol. Chem. 277, 20033-20040). A possible role for His132 in subsequent formation of the Cys133-Cys130 disulfide bond was also noted. To test this proposed mechanism, we have expressed the H137F, H137Q, H132F, H132Q, E118F, E118Q, C133S, and C130S mutants of AhpD, determined the crystal structures of the H137F and H132Q mutants, estimated the pKa values of the cysteine residues, and defined the kinetic properties of the mutant proteins. The collective results strongly support the proposed catalytic mechanism for AhpD.
| + | <jmolCheckbox> |
- | | + | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/me/1me5_consurf.spt"</scriptWhenChecked> |
- | ==About this Structure== | + | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> |
- | 1ME5 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=1ME5 OCA].
| + | <text>to colour the structure by Evolutionary Conservation</text> |
- | | + | </jmolCheckbox> |
- | ==Reference== | + | </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=1me5 ConSurf]. |
- | The mechanism of Mycobacterium tuberculosis alkylhydroperoxidase AhpD as defined by mutagenesis, crystallography, and kinetics., Koshkin A, Nunn CM, Djordjevic S, Ortiz de Montellano PR, J Biol Chem. 2003 Aug 8;278(32):29502-8. Epub 2003 May 21. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/12761216 12761216]
| + | <div style="clear:both"></div> |
| + | == References == |
| + | <references/> |
| + | __TOC__ |
| + | </StructureSection> |
| + | [[Category: Large Structures]] |
| [[Category: Mycobacterium tuberculosis]] | | [[Category: Mycobacterium tuberculosis]] |
- | [[Category: Single protein]]
| + | [[Category: Djordjevic S]] |
- | [[Category: Djordjevic, S.]] | + | [[Category: Nunn CM]] |
- | [[Category: Montellano, P R.Ortiz de.]]
| + | [[Category: Ortiz de Montellano PR]] |
- | [[Category: Nunn, C M.]] | + | |
- | [[Category: Alpha helical]] | + | |
- | [[Category: Trimer]]
| + | |
- | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 00:56:05 2008''
| + | |
| Structural highlights
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
- ↑ 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
- ↑ 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
- ↑ 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
- ↑ 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
- ↑ 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
- ↑ 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
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