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[[ | ==Crystal structure of peroxiredoxin Ahp1 from Saccharomyces cerevisiae in reduced form== | ||
<StructureSection load='4dsr' size='340' side='right' caption='[[4dsr]], [[Resolution|resolution]] 2.91Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[4dsr]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Saccharomyces_cerevisiae Saccharomyces cerevisiae]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4DSR OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4DSR FirstGlance]. <br> | |||
</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4dsq|4dsq]], [[4dss|4dss]]</td></tr> | |||
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">AHP1, L2916, L9354.5, YLR109W ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=4932 Saccharomyces cerevisiae])</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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4dsr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4dsr OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4dsr RCSB], [http://www.ebi.ac.uk/pdbsum/4dsr PDBsum]</span></td></tr> | |||
</table> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Peroxiredoxins (Prxs) are thiol-specific antioxidant proteins that protect cells against reactive oxygen species and are involved in cellular signaling pathways. Alkyl hydroperoxide reductase Ahp1 belongs to the Prx5 subfamily and is a two-cysteine (2-Cys) Prx that forms an intermolecular disulfide bond. Enzymatic assays and bioinformatics enabled us to re-assign the peroxidatic cysteine (C(P)) to Cys-62 and the resolving cysteine (C(R)) to Cys-31 but not the previously reported Cys-120. Thus Ahp1 represents the first 2-Cys Prx with a peroxidatic cysteine after the resolving cysteine in the primary sequence. We also found the positive cooperativity of the substrate t-butyl hydroperoxide binding to Ahp1 homodimer at a Hill coefficient of approximately 2, which enabled Ahp1 to eliminate hydroperoxide at much higher efficiency. To gain the structural insights into the catalytic cycle of Ahp1, we determined the crystal structures of Ahp1 in the oxidized, reduced, and Trx2-complexed forms at 2.40, 2.91, and 2.10 A resolution, respectively. Structural superposition of the oxidized to the reduced form revealed significant conformational changes at the segments containing C(P) and C(R). An intermolecular C(P)-C(R) disulfide bond crossing the A-type dimer interface distinguishes Ahp1 from other typical 2-Cys Prxs. The structure of the Ahp1-Trx2 complex showed for the first time how the electron transfers from thioredoxin to a peroxidase with a thioredoxin-like fold. In addition, site-directed mutagenesis in combination with enzymatic assays suggested that the peroxidase activity of Ahp1 would be altered upon the urmylation (covalently conjugated to ubiquitin-related modifier Urm1) of Lys-32. | |||
Structural Snapshots of Yeast Alkyl Hydroperoxide Reductase Ahp1 Peroxiredoxin Reveal a Novel Two-cysteine Mechanism of Electron Transfer to Eliminate Reactive Oxygen Species.,Lian FM, Yu J, Ma XX, Yu XJ, Chen Y, Zhou CZ J Biol Chem. 2012 May 18;287(21):17077-87. Epub 2012 Apr 2. PMID:22474296<ref>PMID:22474296</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
==See Also== | ==See Also== | ||
*[[Peroxiredoxin|Peroxiredoxin]] | *[[Peroxiredoxin|Peroxiredoxin]] | ||
== References == | |||
== | <references/> | ||
< | __TOC__ | ||
</StructureSection> | |||
[[Category: Peroxiredoxin]] | [[Category: Peroxiredoxin]] | ||
[[Category: Saccharomyces cerevisiae]] | [[Category: Saccharomyces cerevisiae]] | ||
[[Category: Chen, Y | [[Category: Chen, Y]] | ||
[[Category: Lian, F M | [[Category: Lian, F M]] | ||
[[Category: Ma, X X | [[Category: Ma, X X]] | ||
[[Category: Yu, J | [[Category: Yu, J]] | ||
[[Category: Yu, X J | [[Category: Yu, X J]] | ||
[[Category: Zhou, C Z | [[Category: Zhou, C Z]] | ||
[[Category: Alkyl hydroperoxide reductase]] | [[Category: Alkyl hydroperoxide reductase]] | ||
[[Category: Oxidoreductase]] | [[Category: Oxidoreductase]] | ||
[[Category: Peroxidase]] | [[Category: Peroxidase]] | ||
[[Category: Thioredoxin-like fold]] | [[Category: Thioredoxin-like fold]] | ||
Revision as of 18:29, 9 December 2014
Crystal structure of peroxiredoxin Ahp1 from Saccharomyces cerevisiae in reduced formCrystal structure of peroxiredoxin Ahp1 from Saccharomyces cerevisiae in reduced form
Structural highlights
Publication Abstract from PubMedPeroxiredoxins (Prxs) are thiol-specific antioxidant proteins that protect cells against reactive oxygen species and are involved in cellular signaling pathways. Alkyl hydroperoxide reductase Ahp1 belongs to the Prx5 subfamily and is a two-cysteine (2-Cys) Prx that forms an intermolecular disulfide bond. Enzymatic assays and bioinformatics enabled us to re-assign the peroxidatic cysteine (C(P)) to Cys-62 and the resolving cysteine (C(R)) to Cys-31 but not the previously reported Cys-120. Thus Ahp1 represents the first 2-Cys Prx with a peroxidatic cysteine after the resolving cysteine in the primary sequence. We also found the positive cooperativity of the substrate t-butyl hydroperoxide binding to Ahp1 homodimer at a Hill coefficient of approximately 2, which enabled Ahp1 to eliminate hydroperoxide at much higher efficiency. To gain the structural insights into the catalytic cycle of Ahp1, we determined the crystal structures of Ahp1 in the oxidized, reduced, and Trx2-complexed forms at 2.40, 2.91, and 2.10 A resolution, respectively. Structural superposition of the oxidized to the reduced form revealed significant conformational changes at the segments containing C(P) and C(R). An intermolecular C(P)-C(R) disulfide bond crossing the A-type dimer interface distinguishes Ahp1 from other typical 2-Cys Prxs. The structure of the Ahp1-Trx2 complex showed for the first time how the electron transfers from thioredoxin to a peroxidase with a thioredoxin-like fold. In addition, site-directed mutagenesis in combination with enzymatic assays suggested that the peroxidase activity of Ahp1 would be altered upon the urmylation (covalently conjugated to ubiquitin-related modifier Urm1) of Lys-32. Structural Snapshots of Yeast Alkyl Hydroperoxide Reductase Ahp1 Peroxiredoxin Reveal a Novel Two-cysteine Mechanism of Electron Transfer to Eliminate Reactive Oxygen Species.,Lian FM, Yu J, Ma XX, Yu XJ, Chen Y, Zhou CZ J Biol Chem. 2012 May 18;287(21):17077-87. Epub 2012 Apr 2. PMID:22474296[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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