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| | ==Asymmetry in the active site of Mycobacterium tuberculosis AhpE upon exposure to Mycothiol== | | ==Asymmetry in the active site of Mycobacterium tuberculosis AhpE upon exposure to Mycothiol== |
| - | <StructureSection load='5id2' size='340' side='right' caption='[[5id2]], [[Resolution|resolution]] 2.43Å' scene=''> | + | <StructureSection load='5id2' size='340' side='right'caption='[[5id2]], [[Resolution|resolution]] 2.43Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5id2]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5ID2 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5ID2 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5id2]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Mycobacterium_tuberculosis_H37Rv Mycobacterium tuberculosis H37Rv]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5ID2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5ID2 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.43Å</td></tr> |
| - | <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=CSO:S-HYDROXYCYSTEINE'>CSO</scene></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=CSO:S-HYDROXYCYSTEINE'>CSO</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Peroxiredoxin Peroxiredoxin], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.11.1.15 1.11.1.15] </span></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=5id2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5id2 OCA], [https://pdbe.org/5id2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5id2 RCSB], [https://www.ebi.ac.uk/pdbsum/5id2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5id2 ProSAT]</span></td></tr> |
| - | <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=5id2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5id2 OCA], [http://pdbe.org/5id2 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5id2 RCSB], [http://www.ebi.ac.uk/pdbsum/5id2 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5id2 ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/AHPE_MYCTU AHPE_MYCTU] Thiol-specific peroxidase that catalyzes the reduction of hydrogen peroxide and organic hydroperoxides to water and alcohols, respectively. Plays a role in cell protection against oxidative stress by detoxifying peroxides. May represent an important antioxidant defense against cytotoxic peroxides, especially peroxynitrite, which can be formed by activated macrophages during infection.<ref>PMID:19737009</ref> <ref>PMID:24379404</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | ==See Also== | | ==See Also== |
| - | *[[Thioredoxin Reductase|Thioredoxin Reductase]] | + | *[[Thioredoxin reductase 3D structures|Thioredoxin reductase 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Peroxiredoxin]] | + | [[Category: Large Structures]] |
| - | [[Category: Balakrishna, A M]] | + | [[Category: Mycobacterium tuberculosis H37Rv]] |
| - | [[Category: Gruber, G]] | + | [[Category: Balakrishna AM]] |
| - | [[Category: Kumar, A]] | + | [[Category: Gruber G]] |
| - | [[Category: Oxidoreductase]] | + | [[Category: Kumar A]] |
| - | [[Category: Thioredoxin fold]]
| + | |
| Structural highlights
Function
AHPE_MYCTU Thiol-specific peroxidase that catalyzes the reduction of hydrogen peroxide and organic hydroperoxides to water and alcohols, respectively. Plays a role in cell protection against oxidative stress by detoxifying peroxides. May represent an important antioxidant defense against cytotoxic peroxides, especially peroxynitrite, which can be formed by activated macrophages during infection.[1] [2]
Publication Abstract from PubMed
Mycobacterium tuberculosis (Mtb) has the ability to persist within the human host for a long time in a dormant stage and re-merges when the immune system is compromised. The pathogenic bacterium employs an elaborate antioxidant defence machinery composed of the mycothiol- and thioredoxin system in addition to a superoxide dismutase, a catalase, and peroxiredoxins (Prxs). Among the family of Peroxiredoxins, Mtb expresses a 1-cysteine peroxiredoxin, known as alkylhydroperoxide reductase E (MtAhpE), and defined as a potential tuberculosis drug target. The reduced MtAhpE (MtAhpE-SH) scavenges peroxides to become converted to MtAhpE-SOH. To provide continuous availability of MtAhpE-SH, MtAhpE-SOH has to become reduced. Here, we used NMR spectroscopy to delineate the reduced (MtAhpE-SH), sulphenic (MtAhpE-SOH) and sulphinic (MtAhpE-SO2H) states of MtAhpE through cysteinyl-labelling, and provide for the first time evidence of a mycothiol-dependent mechanism of MtAhpE reduction. This is confirmed by crystallographic studies, wherein MtAhpE was crystallised in the presence of mycothiol and the structure was solved at 2.43A resolution. Combined with NMR-studies, the crystallographic structures reveal conformational changes of important residues during the catalytic cycle of MtAhpE. In addition, alterations of the overall protein in solution due to redox modulation are observed by small angle X-ray scattering (SAXS) studies. Finally, by employing SAXS and dynamic light scattering, insight is provided into the most probable physiological oligomeric state of MtAhpE necessary for activity, being also discussed in the context of concerted substrate binding inside the dimeric MtAhpE.
Redox chemistry of Mycobacterium tuberculosis alkylhydroperoxide reductase E (AhpE): Structural and mechanistic insight into a mycoredoxin-1 independent reductive pathway of AhpE via mycothiol.,Kumar A, Balakrishna AM, Nartey W, Manimekalai MS, Gruber G Free Radic Biol Med. 2016 Jul 11. pii: S0891-5849(16)30327-6. doi:, 10.1016/j.freeradbiomed.2016.07.007. PMID:27417938[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Hugo M, Turell L, Manta B, Botti H, Monteiro G, Netto LE, Alvarez B, Radi R, Trujillo M. Thiol and sulfenic acid oxidation of AhpE, the one-cysteine peroxiredoxin from Mycobacterium tuberculosis: kinetics, acidity constants, and conformational dynamics. Biochemistry. 2009 Oct 13;48(40):9416-26. PMID:19737009 doi:10.1021/bi901221s
- ↑ Hugo M, Van Laer K, Reyes AM, Vertommen D, Messens J, Radi R, Trujillo M. Mycothiol/mycoredoxin 1-dependent reduction of the peroxiredoxin AhpE from Mycobacterium tuberculosis. J Biol Chem. 2014 Feb 21;289(8):5228-39. PMID:24379404 doi:10.1074/jbc.M113.510248
- ↑ Kumar A, Balakrishna AM, Nartey W, Manimekalai MS, Gruber G. Redox chemistry of Mycobacterium tuberculosis alkylhydroperoxide reductase E (AhpE): Structural and mechanistic insight into a mycoredoxin-1 independent reductive pathway of AhpE via mycothiol. Free Radic Biol Med. 2016 Jul 11. pii: S0891-5849(16)30327-6. doi:, 10.1016/j.freeradbiomed.2016.07.007. PMID:27417938 doi:http://dx.doi.org/10.1016/j.freeradbiomed.2016.07.007
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