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| | <StructureSection load='1pv1' size='340' side='right'caption='[[1pv1]], [[Resolution|resolution]] 2.30Å' scene=''> | | <StructureSection load='1pv1' size='340' side='right'caption='[[1pv1]], [[Resolution|resolution]] 2.30Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[1pv1]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Atcc_18824 Atcc 18824]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1PV1 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=1PV1 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[1pv1]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Saccharomyces_cerevisiae Saccharomyces cerevisiae]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1PV1 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1PV1 FirstGlance]. <br> |
| - | </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">YJL068C, J1102 OR HRE299 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=4932 ATCC 18824])</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]] 2.3Å</td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=1pv1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1pv1 OCA], [http://pdbe.org/1pv1 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1pv1 RCSB], [http://www.ebi.ac.uk/pdbsum/1pv1 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1pv1 ProSAT], [http://www.topsan.org/Proteins/NYSGXRC/1pv1 TOPSAN]</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=1pv1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1pv1 OCA], [https://pdbe.org/1pv1 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1pv1 RCSB], [https://www.ebi.ac.uk/pdbsum/1pv1 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1pv1 ProSAT], [https://www.topsan.org/Proteins/NYSGXRC/1pv1 TOPSAN]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/SFGH_YEAST SFGH_YEAST]] Serine hydrolase involved in the detoxification of formaldehyde. | + | [https://www.uniprot.org/uniprot/SFGH_YEAST SFGH_YEAST] Serine hydrolase involved in the detoxification of formaldehyde. |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | <jmolCheckbox> | | <jmolCheckbox> |
| | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/pv/1pv1_consurf.spt"</scriptWhenChecked> | | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/pv/1pv1_consurf.spt"</scriptWhenChecked> |
| - | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | + | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked> |
| | <text>to colour the structure by Evolutionary Conservation</text> | | <text>to colour the structure by Evolutionary Conservation</text> |
| | </jmolCheckbox> | | </jmolCheckbox> |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Atcc 18824]] | |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Burley, S K]] | + | [[Category: Saccharomyces cerevisiae]] |
| - | [[Category: Eswaramoorthy, S]] | + | [[Category: Burley SK]] |
| - | [[Category: Kumaran, D]] | + | [[Category: Eswaramoorthy S]] |
| - | [[Category: Millard, C]] | + | [[Category: Kumaran D]] |
| - | [[Category: Structural genomic]]
| + | [[Category: Millard C]] |
| - | [[Category: Swaminathan, S]] | + | [[Category: Swaminathan S]] |
| - | [[Category: Esterase]]
| + | |
| - | [[Category: Hydrolase]]
| + | |
| - | [[Category: Hypothetical]]
| + | |
| - | [[Category: NYSGXRC, New York SGX Research Center for Structural Genomics]]
| + | |
| - | [[Category: PSI, Protein structure initiative]]
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| Structural highlights
Function
SFGH_YEAST Serine hydrolase involved in the detoxification of formaldehyde.
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
Saccharomyces cerevisiae expresses a 67.8 kDa homodimeric serine thioesterase, S-formylglutathione hydrolase (SFGH), that is 39.9% identical with human esterase D. Both enzymes possess significant carboxylesterase and S-formylglutathione thioesterase activity but are unusually resistant to organophosphate (OP) inhibitors. We determined the X-ray crystal structure of yeast (y) SFGH to 2.3 A resolution by multiwavelength anomalous dispersion and used the structure to guide site-specific mutagenesis experiments addressing substrate and inhibitor reactivity. Our results demonstrate a steric mechanism of OP resistance mediated by a single indole ring (W197) located in an enzyme "acyl pocket". The W197I substitution enhances ySFGH reactivity with paraoxon by >1000-fold ( k i (W197I) = 16 +/- 2 mM (-1) h (-1)), thereby overcoming natural OP resistance. W197I increases the rate of OP inhibition under pseudo-first-order conditions but does not accelerate OP hydrolysis. The structure of the paraoxon-inhibited W197I variant was determined by molecular replacement (2.2 A); it revealed a stabilized sulfenic acid at Cys60. Wild-type (WT) ySFGH is inhibited by thiol reactive compounds and is sensitive to oxidation; thus, the cysteine sulfenic acid may play a role in the regulation of a "D-type" esterase. The structure of the W197I variant is the first reported cysteine sulfenic acid in a serine esterase. We constructed five Cys60/W197I variants and show that introducing a positive charge near the oxyanion hole, W197I/C60R or W197I/C60K, results in a further enhancement of the rates of phosphorylation with paraoxon ( k i = 42 or 80 mM (-1) h (-1), respectively) but does not affect the dephosphorylation of the enzyme. We also characterized three histidine substitutions near the oxyanion hole, G57H, L58H, and M162H, which significantly decrease esterase activity.
Structural characterization and reversal of the natural organophosphate resistance of a D-type esterase, Saccharomyces cerevisiae S-formylglutathione hydrolase.,Legler PM, Kumaran D, Swaminathan S, Studier FW, Millard CB Biochemistry. 2008 Sep 9;47(36):9592-601. Epub 2008 Aug 16. PMID:18707125[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Legler PM, Kumaran D, Swaminathan S, Studier FW, Millard CB. Structural characterization and reversal of the natural organophosphate resistance of a D-type esterase, Saccharomyces cerevisiae S-formylglutathione hydrolase. Biochemistry. 2008 Sep 9;47(36):9592-601. Epub 2008 Aug 16. PMID:18707125 doi:http://dx.doi.org/10.1021/bi8010016
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