4fol - Revision history

OCA at 15:30, 14 March 2024

2024-03-14T15:30:47Z

←Older revision		Revision as of 15:30, 14 March 2024
Line 4:		Line 4:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4fol]] 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=4FOL OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4FOL FirstGlance]. <br>		<table><tr><td colspan='2'>[[4fol]] 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=4FOL OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4FOL FirstGlance]. <br>
-	</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=4fol FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4fol OCA], [https://pdbe.org/4fol PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4fol RCSB], [https://www.ebi.ac.uk/pdbsum/4fol PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4fol ProSAT]</span></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]] 2.07Å</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=4fol FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4fol OCA], [https://pdbe.org/4fol PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4fol RCSB], [https://www.ebi.ac.uk/pdbsum/4fol PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4fol ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
	[https://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.
-	<div style="background-color:#fffaf0;">
-	== Publication Abstract from PubMed ==
-	While the general catalytic mechanism of the widespread serine hydrolase superfamily has been documented extensively, much less is known about its varied modes of functional modulation within biological systems. Under oxidizing conditions, inhibition of Saccharomyces cerevisiae S-formylglutathione hydrolase (SFGH, homologous to human esterase D) activity is attributable to a cysteine (Cys-60) adjacent to its catalytic triad and approximately 8.0A away from the Ogamma of the nucleophilic serine. Cys-60 is oxidized to a sulfenic acid in the structure of the Paraoxon-inhibited W197I variant (PDB 3C6B). The structural snap-shot captured an unstable reversibly oxidized state, but it remained unclear as to whether the oxidation occurred before, during, or after the reaction with the organophosphate inhibitor. To determine if the oxidation of Cys-60 was functionally linked to ester hydrolysis, we used kinetic analysis and site-directed mutagenesis in combination with X-ray crystallography. The essential nature of Cys-60 for oxidation is demonstrated by the C60S variant, which is not inhibited by peroxide in the presence or absence of substrate. In the presence of substrate, the rate of inhibition of the WT SFGH by peroxide increases 14-fold, suggesting uncompetitive behavior linking oxidation to ester hydrolysis. Here we found one variant, H160I, which is activated by peroxide. This variant is activated at comparable rates in the presence or absence of substrate, indicating that the conserved His-160 is involved in the inhibitory mechanism linking ester hydrolysis to the oxidation of Cys-60. Copper chloride inhibition experiments show that at least two metal ions bind and inhibit both WT and H160I. A structure of the Paraoxon-inhibited W197I variant soaked with CuCl(2) shows density for one metal ion per monomer at the N-terminus, and density around the Cys-60 sulfur consistent with a sulfinic acid, Cys-SO(2). A Dali structural similarity search uncovered two other enzymes (Bacillis subtilis RsbQ, 1WOM and Clostridium acetobutylicum Lipase-esterase, 3E0X) that contain a similar Cys adjacent to a catalytic triad. We speculate that the regulatory motif uncovered is conserved in some D-type esterases and discuss its structural similarities in the active site of human protective protein (HPP; also known as Cathepsin A).
-
-	A role for His-160 in peroxide inhibition of S. cerevisiae S-formylglutathione hydrolase: Evidence for an oxidation sensitive motif.,Legler PM, Leary DH, Hervey WJ 4th, Millard CB Arch Biochem Biophys. 2012 Aug 13. PMID:22906720<ref>PMID:22906720</ref>
-
-	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	</div>
-	<div class="pdbe-citations 4fol" style="background-color:#fffaf0;"></div>
-	== References ==
-	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>

OCA at 20:03, 19 October 2022

2022-10-19T20:03:35Z

←Older revision		Revision as of 20:03, 19 October 2022
Line 1:		Line 1:

	==S-formylglutathione hydrolase Variant H160I==		==S-formylglutathione hydrolase Variant H160I==
-	<StructureSection load='4fol' size='340' side='right' caption='[[4fol]], [[Resolution\|resolution]] 2.07Å' scene=''>	+	<StructureSection load='4fol' size='340' side='right'caption='[[4fol]], [[Resolution\|resolution]] 2.07Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4fol]] 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=4FOL OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=4FOL FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4fol]] 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=4FOL OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4FOL FirstGlance]. <br>
-	</td></tr>~~<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1pv1\|1pv1]], [[3c6b\|3c6b]], [[4flm\|4flm]]</td></tr>~~	+	</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=4fol FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4fol OCA], [https://pdbe.org/4fol PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4fol RCSB], [https://www.ebi.ac.uk/pdbsum/4fol PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4fol ProSAT]</span></td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">YJL068C, HRE299, J1102 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=4932 ATCC 18824])</td></tr>	+
-	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/S-formylglutathione_hydrolase S-formylglutathione hydrolase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.1.2.12 3.1.2.12] </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=4fol FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4fol OCA], [~~http~~://pdbe.org/4fol PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=4fol RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/4fol PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=4fol ProSAT]</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.
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 24:		Line 21:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Atcc 18824~~]]	+	[[Category: Large Structures]]
-	[[Category: ~~S-formylglutathione hydrolase~~]]	+	[[Category: Saccharomyces cerevisiae]]
-	[[Category: Legler~~, P M~~]]	+	[[Category: Legler PM]]
-	[[Category: Millard~~, C B]]~~	+	[[Category: Millard CB]]
-	~~[[Category: D-type esterase]]~~	+
-	~~[[Category: Esterase activity activation]]~~	+
-	~~[[Category: Esterase activity inhibition]]~~	+
-	~~[[Category: Hydrolase]]~~	+
-	~~[[Category: Oxidation sensor motif~~]]	+

OCA at 14:46, 4 August 2016

2016-08-04T14:46:52Z

←Older revision		Revision as of 14:46, 4 August 2016
Line 1:		Line 1:
		+
	==S-formylglutathione hydrolase Variant H160I==		==S-formylglutathione hydrolase Variant H160I==
	<StructureSection load='4fol' size='340' side='right' caption='[[4fol]], [[Resolution\|resolution]] 2.07Å' scene=''>		<StructureSection load='4fol' size='340' side='right' caption='[[4fol]], [[Resolution\|resolution]] 2.07Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4fol]] 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=4FOL OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4FOL FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4fol]] 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=4FOL OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4FOL FirstGlance]. <br>
	</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1pv1\|1pv1]], [[3c6b\|3c6b]], [[4flm\|4flm]]</td></tr>		</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1pv1\|1pv1]], [[3c6b\|3c6b]], [[4flm\|4flm]]</td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">YJL068C, HRE299, J1102 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=4932 ~~Saccharomyces cerevisiae~~])</td></tr>	+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">YJL068C, HRE299, J1102 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=4932 ATCC 18824])</td></tr>
	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/S-formylglutathione_hydrolase S-formylglutathione hydrolase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.1.2.12 3.1.2.12] </span></td></tr>		<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/S-formylglutathione_hydrolase S-formylglutathione hydrolase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.1.2.12 3.1.2.12] </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=4fol FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4fol OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4fol RCSB], [http://www.ebi.ac.uk/pdbsum/4fol PDBsum]</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=4fol FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4fol OCA], [http://pdbe.org/4fol PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4fol RCSB], [http://www.ebi.ac.uk/pdbsum/4fol PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4fol ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
Line 18:		Line 19:
	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>		From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
	</div>		</div>
		+	<div class="pdbe-citations 4fol" style="background-color:#fffaf0;"></div>
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Atcc 18824]]
	[[Category: S-formylglutathione hydrolase]]		[[Category: S-formylglutathione hydrolase]]
-	[[Category: Saccharomyces cerevisiae]]
	[[Category: Legler, P M]]		[[Category: Legler, P M]]
	[[Category: Millard, C B]]		[[Category: Millard, C B]]

OCA at 15:56, 24 December 2014

2014-12-24T15:56:41Z

←Older revision		Revision as of 15:56, 24 December 2014
Line 3:		Line 3:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4fol]] 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=4FOL OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4FOL FirstGlance]. <br>		<table><tr><td colspan='2'>[[4fol]] 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=4FOL OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4FOL FirstGlance]. <br>
-	</td></tr><tr><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1pv1\|1pv1]], [[3c6b\|3c6b]], [[4flm\|4flm]]</td></tr>	+	</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1pv1\|1pv1]], [[3c6b\|3c6b]], [[4flm\|4flm]]</td></tr>
-	<tr><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">YJL068C, HRE299, J1102 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=4932 Saccharomyces cerevisiae])</td></tr>	+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">YJL068C, HRE299, J1102 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=4932 Saccharomyces cerevisiae])</td></tr>
-	<tr><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/S-formylglutathione_hydrolase S-formylglutathione hydrolase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.1.2.12 3.1.2.12] </span></td></tr>	+	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/S-formylglutathione_hydrolase S-formylglutathione hydrolase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.1.2.12 3.1.2.12] </span></td></tr>
-	<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4fol FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4fol OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4fol RCSB], [http://www.ebi.ac.uk/pdbsum/4fol PDBsum]</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=4fol FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4fol OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4fol RCSB], [http://www.ebi.ac.uk/pdbsum/4fol PDBsum]</span></td></tr>
-	<table>	+	</table>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/SFGH_YEAST SFGH_YEAST]] Serine hydrolase involved in the detoxification of formaldehyde.
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 22:		Line 24:
	[[Category: S-formylglutathione hydrolase]]		[[Category: S-formylglutathione hydrolase]]
	[[Category: Saccharomyces cerevisiae]]		[[Category: Saccharomyces cerevisiae]]
-	[[Category: Legler, P M.]]	+	[[Category: Legler, P M]]
-	[[Category: Millard, C B.]]	+	[[Category: Millard, C B]]
	[[Category: D-type esterase]]		[[Category: D-type esterase]]
	[[Category: Esterase activity activation]]		[[Category: Esterase activity activation]]

OCA at 07:50, 9 July 2014

2014-07-09T07:50:43Z

←Older revision		Revision as of 07:50, 9 July 2014
Line 1:		Line 1:
-	[[~~Image:~~4fol.~~png~~\|~~left~~\|~~200px~~]]	+	==S-formylglutathione hydrolase Variant H160I==
		+	<StructureSection load='4fol' size='340' side='right' caption='[[4fol]], [[Resolution\|resolution]] 2.07Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[4fol]] 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=4FOL OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4FOL FirstGlance]. <br>
		+	</td></tr><tr><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1pv1\|1pv1]], [[3c6b\|3c6b]], [[4flm\|4flm]]</td></tr>
		+	<tr><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">YJL068C, HRE299, J1102 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=4932 Saccharomyces cerevisiae])</td></tr>
		+	<tr><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/S-formylglutathione_hydrolase S-formylglutathione hydrolase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.1.2.12 3.1.2.12] </span></td></tr>
		+	<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4fol FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4fol OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4fol RCSB], [http://www.ebi.ac.uk/pdbsum/4fol PDBsum]</span></td></tr>
		+	<table>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	While the general catalytic mechanism of the widespread serine hydrolase superfamily has been documented extensively, much less is known about its varied modes of functional modulation within biological systems. Under oxidizing conditions, inhibition of Saccharomyces cerevisiae S-formylglutathione hydrolase (SFGH, homologous to human esterase D) activity is attributable to a cysteine (Cys-60) adjacent to its catalytic triad and approximately 8.0A away from the Ogamma of the nucleophilic serine. Cys-60 is oxidized to a sulfenic acid in the structure of the Paraoxon-inhibited W197I variant (PDB 3C6B). The structural snap-shot captured an unstable reversibly oxidized state, but it remained unclear as to whether the oxidation occurred before, during, or after the reaction with the organophosphate inhibitor. To determine if the oxidation of Cys-60 was functionally linked to ester hydrolysis, we used kinetic analysis and site-directed mutagenesis in combination with X-ray crystallography. The essential nature of Cys-60 for oxidation is demonstrated by the C60S variant, which is not inhibited by peroxide in the presence or absence of substrate. In the presence of substrate, the rate of inhibition of the WT SFGH by peroxide increases 14-fold, suggesting uncompetitive behavior linking oxidation to ester hydrolysis. Here we found one variant, H160I, which is activated by peroxide. This variant is activated at comparable rates in the presence or absence of substrate, indicating that the conserved His-160 is involved in the inhibitory mechanism linking ester hydrolysis to the oxidation of Cys-60. Copper chloride inhibition experiments show that at least two metal ions bind and inhibit both WT and H160I. A structure of the Paraoxon-inhibited W197I variant soaked with CuCl(2) shows density for one metal ion per monomer at the N-terminus, and density around the Cys-60 sulfur consistent with a sulfinic acid, Cys-SO(2). A Dali structural similarity search uncovered two other enzymes (Bacillis subtilis RsbQ, 1WOM and Clostridium acetobutylicum Lipase-esterase, 3E0X) that contain a similar Cys adjacent to a catalytic triad. We speculate that the regulatory motif uncovered is conserved in some D-type esterases and discuss its structural similarities in the active site of human protective protein (HPP; also known as Cathepsin A).

-	~~{{STRUCTURE_4fol\| PDB=4fol \| SCENE= }}~~	+	A role for His-160 in peroxide inhibition of S. cerevisiae S-formylglutathione hydrolase: Evidence for an oxidation sensitive motif.,Legler PM, Leary DH, Hervey WJ 4th, Millard CB Arch Biochem Biophys. 2012 Aug 13. PMID:22906720<ref>PMID:22906720</ref>

-	~~===~~S~~-formylglutathione hydrolase Variant H160I===~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-		+	</div>
-	~~{{ABSTRACT_PUBMED_22906720}}~~	+	== References ==
-		+	<references/>
-	==~~About this Structure~~==	+	__TOC__
-	~~[[4fol]] 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=4FOL OCA].~~	+	</StructureSection>
	[[Category: S-formylglutathione hydrolase]]		[[Category: S-formylglutathione hydrolase]]
	[[Category: Saccharomyces cerevisiae]]		[[Category: Saccharomyces cerevisiae]]

OCA at 06:36, 3 October 2012

2012-10-03T06:36:41Z

←Older revision		Revision as of 06:36, 3 October 2012
Line 1:		Line 1:
-	[[Image:4fol.~~jpg~~\|left\|200px]]	+	[[Image:4fol.png\|left\|200px]]

	{{STRUCTURE_4fol\| PDB=4fol \| SCENE= }}		{{STRUCTURE_4fol\| PDB=4fol \| SCENE= }}

OCA at 05:38, 5 September 2012

2012-09-05T05:38:57Z

←Older revision		Revision as of 05:38, 5 September 2012
Line 1:		Line 1:
-	~~'''Unreleased structure'''~~	+	[[Image:4fol.jpg\|left\|200px]]

-	~~The entry~~ 4fol ~~is ON HOLD~~ ~~until Paper Publication~~	+	{{STRUCTURE_4fol\| PDB=4fol \| SCENE= }}

-	~~Authors: Legler, P.M., Millard, C.B.~~	+	===S-formylglutathione hydrolase Variant H160I===

-	~~Description~~: S-formylglutathione hydrolase ~~Variant H160I~~	+	{{ABSTRACT_PUBMED_22906720}}
		+
		+	==About this Structure==
		+	[[4fol]] 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=4FOL OCA].
		+	[[Category: S-formylglutathione hydrolase]]
		+	[[Category: Saccharomyces cerevisiae]]
		+	[[Category: Legler, P M.]]
		+	[[Category: Millard, C B.]]
		+	[[Category: D-type esterase]]
		+	[[Category: Esterase activity activation]]
		+	[[Category: Esterase activity inhibition]]
		+	[[Category: Hydrolase]]
		+	[[Category: Oxidation sensor motif]]

OCA at 05:28, 22 August 2012

2012-08-22T05:28:55Z

←Older revision		Revision as of 05:28, 22 August 2012
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 4fol is ON HOLD	+	The entry 4fol is ON HOLD until Paper Publication

	Authors: Legler, P.M., Millard, C.B.		Authors: Legler, P.M., Millard, C.B.

	Description: S-formylglutathione hydrolase Variant H160I		Description: S-formylglutathione hydrolase Variant H160I

OCA: Protected "4fol" [edit=sysop:move=sysop]

2012-06-27T05:29:00Z

Protected "4fol" [edit=sysop:move=sysop]

←Older revision

Revision as of 05:29, 27 June 2012

OCA: New page: '''Unreleased structure''' The entry 4fol is ON HOLD Authors: Legler, P.M., Millard, C.B. Description: S-formylglutathione hydrolase Variant H160I

2012-06-27T05:29:00Z

New page: '''Unreleased structure''' The entry 4fol is ON HOLD Authors: Legler, P.M., Millard, C.B. Description: S-formylglutathione hydrolase Variant H160I

New page

'''Unreleased structure'''

The entry 4fol is ON HOLD

Authors: Legler, P.M., Millard, C.B.

Description: S-formylglutathione hydrolase Variant H160I