4fqf - Revision history

OCA at 15:31, 14 March 2024

2024-03-14T15:31:36Z

←Older revision		Revision as of 15:31, 14 March 2024
Line 4:		Line 4:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4fqf]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4FQF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4FQF FirstGlance]. <br>		<table><tr><td colspan='2'>[[4fqf]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4FQF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4FQF FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=2NO:NITROGEN+DIOXIDE'>2NO</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=NAD:NICOTINAMIDE-ADENINE-DINUCLEOTIDE'>NAD</scene>, <scene name='pdbligand=URE:UREA'>URE</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]] 2.281Å</td></tr>
		+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=2NO:NITROGEN+DIOXIDE'>2NO</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=NAD:NICOTINAMIDE-ADENINE-DINUCLEOTIDE'>NAD</scene>, <scene name='pdbligand=URE:UREA'>URE</scene></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=4fqf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4fqf OCA], [https://pdbe.org/4fqf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4fqf RCSB], [https://www.ebi.ac.uk/pdbsum/4fqf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4fqf ProSAT]</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=4fqf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4fqf OCA], [https://pdbe.org/4fqf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4fqf RCSB], [https://www.ebi.ac.uk/pdbsum/4fqf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4fqf ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
	[https://www.uniprot.org/uniprot/ALDH2_HUMAN ALDH2_HUMAN]		[https://www.uniprot.org/uniprot/ALDH2_HUMAN ALDH2_HUMAN]
-	<div style="background-color:#fffaf0;">
-	== Publication Abstract from PubMed ==
-	Aldehyde dehydrogenase-2 (ALDH2) catalyzes the bioactivation of nitroglycerin (glyceryl trinitrate, GTN) in blood vessels, resulting in vasodilation by nitric oxide (NO) or a related species. Because the mechanism of this reaction is still unclear we determined the three-dimensional structures of wild-type (WT) ALDH2 and of a triple mutant of the protein that exhibits low denitration activity (E268Q/C301S/C303S) in complex with GTN. The structure of the triple mutant showed that GTN binds to the active site via polar contacts to the oxyanion hole and to residues 268 and 301 as well as by van der Waals interactions to hydrophobic residues of the catalytic pocket. The structure of the GTN-soaked wild-type protein revealed a thionitrate adduct to Cys-302 as the first reaction intermediate, which was also found by mass spectrometry (MS) experiments. In addition, the MS data identified sulfinic acid as the irreversibly inactivated enzyme species. Assuming that the structures of the triple mutant and wild-type ALDH2 reflect binding of GTN to the catalytic site and the first reaction step, respectively, superposition of the two structures indicates that denitration of GTN is initiated by nucleophilic attack of Cys-302 at one of the terminal nitrate groups, resulting in formation of the observed thionitrate intermediate and release of 1,2-glyceryl dinitrate. Our results shed light on the molecular mechanism of the GTN denitration reaction and provide useful information on the structural requirements for high affinity binding of organic nitrates to the catalytic site of ALDH2.
-
-	Vascular Bioactivation of Nitroglycerin by Aldehyde Dehydrogenase-2: REACTION INTERMEDIATES REVEALED BY CRYSTALLOGRAPHY AND MASS SPECTROMETRY.,Lang BS, Gorren AC, Oberdorfer G, Wenzl MV, Furdui CM, Poole LB, Mayer B, Gruber K J Biol Chem. 2012 Nov 2;287(45):38124-34. doi: 10.1074/jbc.M112.371716. Epub 2012, Sep 17. PMID:22988236<ref>PMID:22988236</ref>
-
-	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	</div>
-	<div class="pdbe-citations 4fqf" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==
	*[[Aldehyde dehydrogenase 3D structures\|Aldehyde dehydrogenase 3D structures]]		*[[Aldehyde dehydrogenase 3D structures\|Aldehyde dehydrogenase 3D structures]]
-	== References ==
-	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>

OCA at 20:05, 19 October 2022

2022-10-19T20:05:38Z

←Older revision		Revision as of 20:05, 19 October 2022
Line 1:		Line 1:

	==Crystal structure of a thionitrate intermediate of human aldehyde dehydrogenase-2==		==Crystal structure of a thionitrate intermediate of human aldehyde dehydrogenase-2==
-	<StructureSection load='4fqf' size='340' side='right' caption='[[4fqf]], [[Resolution\|resolution]] 2.28Å' scene=''>	+	<StructureSection load='4fqf' size='340' side='right'caption='[[4fqf]], [[Resolution\|resolution]] 2.28Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4fqf]] is a 4 chain structure with sequence from [~~http~~://en.wikipedia.org/wiki/~~Human Human~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4FQF OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=4FQF FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4fqf]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4FQF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4FQF FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=2NO:NITROGEN+DIOXIDE'>2NO</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=NAD:NICOTINAMIDE-ADENINE-DINUCLEOTIDE'>NAD</scene>, <scene name='pdbligand=URE:UREA'>URE</scene~~></td></tr>~~	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=2NO:NITROGEN+DIOXIDE'>2NO</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=NAD:NICOTINAMIDE-ADENINE-DINUCLEOTIDE'>NAD</scene>, <scene name='pdbligand=URE:UREA'>URE</scene></td></tr>
-	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1zum\|1zum]], [[3n80\|3n80]], [[3n81\|3n81]], [[3n82\|3n82]], [[3n83\|3n83]], [[2onm\|2onm]], [[3inl\|3inl]], [[3sz9\|3sz9]], [[2onn\|2onn]], [[1o05\|1o05]], [[2ono\|2ono]], [[3inj\|3inj]], [[1nzw\|1nzw]], [[1nzx\|1nzx]], [[1nzz\|1nzz]], [[1o00\|1o00]], [[1o01\|1o01]], [[1o02\|1o02]], [[1o04\|1o04]], [[2onp\|2onp]], [[2vle\|2vle]]</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=4fqf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4fqf OCA], [https://pdbe.org/4fqf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4fqf RCSB], [https://www.ebi.ac.uk/pdbsum/4fqf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4fqf ProSAT]</span></td></tr>
-	~~<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">ALDH2, ALDM ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>~~	+
-	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Aldehyde_dehydrogenase_(NAD(+)) Aldehyde dehydrogenase (NAD(+))], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.2.1.3 1.2.1.3] </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=4fqf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4fqf OCA], [~~http~~://pdbe.org/4fqf PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=4fqf RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/4fqf PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=4fqf ProSAT]</span></td></tr>	+
	</table>		</table>
		+	== Function ==
		+	[https://www.uniprot.org/uniprot/ALDH2_HUMAN ALDH2_HUMAN]
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 21:		Line 20:

	==See Also==		==See Also==
-	*[[Aldehyde dehydrogenase\|Aldehyde dehydrogenase]]	+	*[[Aldehyde dehydrogenase 3D structures\|Aldehyde dehydrogenase 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Human~~]]	+	[[Category: Homo sapiens]]
-	[[Category: ~~Gruber, K~~]]	+	[[Category: Large Structures]]
-	[[Category: ~~Lang, B S~~]]	+	[[Category: Gruber K]]
-	[[Category: ~~Aldehyde]]~~	+	[[Category: Lang BS]]
-	~~[[Category: Ester]]~~	+
-	~~[[Category: Nad]]~~	+
-	~~[[Category: Organic nitrate]]~~	+
-	~~[[Category: Oxidoreductase]]~~	+
-	~~[[Category: Oxidoreductase-intermediate complex]]~~	+
-	~~[[Category: Rossmann fold~~]]	+

OCA at 20:06, 15 December 2016

2016-12-15T20:06:39Z

←Older revision		Revision as of 20:06, 15 December 2016
Line 1:		Line 1:
		+
	==Crystal structure of a thionitrate intermediate of human aldehyde dehydrogenase-2==		==Crystal structure of a thionitrate intermediate of human aldehyde dehydrogenase-2==
	<StructureSection load='4fqf' size='340' side='right' caption='[[4fqf]], [[Resolution\|resolution]] 2.28Å' scene=''>		<StructureSection load='4fqf' size='340' side='right' caption='[[4fqf]], [[Resolution\|resolution]] 2.28Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4fqf]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/~~Homo_sapiens Homo sapiens~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4FQF OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4FQF FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4fqf]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4FQF OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4FQF FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=2NO:NITROGEN+DIOXIDE'>2NO</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=NAD:NICOTINAMIDE-ADENINE-DINUCLEOTIDE'>NAD</scene>, <scene name='pdbligand=URE:UREA'>URE</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=2NO:NITROGEN+DIOXIDE'>2NO</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=NAD:NICOTINAMIDE-ADENINE-DINUCLEOTIDE'>NAD</scene>, <scene name='pdbligand=URE:UREA'>URE</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1zum\|1zum]], [[3n80\|3n80]], [[3n81\|3n81]], [[3n82\|3n82]], [[3n83\|3n83]], [[2onm\|2onm]], [[3inl\|3inl]], [[3sz9\|3sz9]], [[2onn\|2onn]], [[1o05\|1o05]], [[2ono\|2ono]], [[3inj\|3inj]], [[1nzw\|1nzw]], [[1nzx\|1nzx]], [[1nzz\|1nzz]], [[1o00\|1o00]], [[1o01\|1o01]], [[1o02\|1o02]], [[1o04\|1o04]], [[2onp\|2onp]], [[2vle\|2vle]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1zum\|1zum]], [[3n80\|3n80]], [[3n81\|3n81]], [[3n82\|3n82]], [[3n83\|3n83]], [[2onm\|2onm]], [[3inl\|3inl]], [[3sz9\|3sz9]], [[2onn\|2onn]], [[1o05\|1o05]], [[2ono\|2ono]], [[3inj\|3inj]], [[1nzw\|1nzw]], [[1nzx\|1nzx]], [[1nzz\|1nzz]], [[1o00\|1o00]], [[1o01\|1o01]], [[1o02\|1o02]], [[1o04\|1o04]], [[2onp\|2onp]], [[2vle\|2vle]]</td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">ALDH2, ALDM ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 ~~Homo sapiens~~])</td></tr>	+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">ALDH2, ALDM ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Aldehyde_dehydrogenase_(NAD(+)) Aldehyde dehydrogenase (NAD(+))], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.2.1.3 1.2.1.3] </span></td></tr>		<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Aldehyde_dehydrogenase_(NAD(+)) Aldehyde dehydrogenase (NAD(+))], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.2.1.3 1.2.1.3] </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=4fqf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4fqf OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4fqf RCSB], [http://www.ebi.ac.uk/pdbsum/4fqf 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=4fqf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4fqf OCA], [http://pdbe.org/4fqf PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4fqf RCSB], [http://www.ebi.ac.uk/pdbsum/4fqf PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4fqf ProSAT]</span></td></tr>
	</table>		</table>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
Line 17:		Line 18:
	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 4fqf" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==
Line 24:		Line 26:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Homo sapiens~~]]	+	[[Category: Human]]
	[[Category: Gruber, K]]		[[Category: Gruber, K]]
	[[Category: Lang, B S]]		[[Category: Lang, B S]]

OCA at 17:50, 9 December 2014

2014-12-09T17:50:34Z

←Older revision		Revision as of 17:50, 9 December 2014
Line 1:		Line 1:
-	[[~~Image:~~4fqf.~~png~~\|~~left~~\|~~200px~~]]	+	==Crystal structure of a thionitrate intermediate of human aldehyde dehydrogenase-2==
		+	<StructureSection load='4fqf' size='340' side='right' caption='[[4fqf]], [[Resolution\|resolution]] 2.28Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[4fqf]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4FQF OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4FQF FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=2NO:NITROGEN+DIOXIDE'>2NO</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=NAD:NICOTINAMIDE-ADENINE-DINUCLEOTIDE'>NAD</scene>, <scene name='pdbligand=URE:UREA'>URE</scene></td></tr>
		+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1zum\|1zum]], [[3n80\|3n80]], [[3n81\|3n81]], [[3n82\|3n82]], [[3n83\|3n83]], [[2onm\|2onm]], [[3inl\|3inl]], [[3sz9\|3sz9]], [[2onn\|2onn]], [[1o05\|1o05]], [[2ono\|2ono]], [[3inj\|3inj]], [[1nzw\|1nzw]], [[1nzx\|1nzx]], [[1nzz\|1nzz]], [[1o00\|1o00]], [[1o01\|1o01]], [[1o02\|1o02]], [[1o04\|1o04]], [[2onp\|2onp]], [[2vle\|2vle]]</td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">ALDH2, ALDM ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr>
		+	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Aldehyde_dehydrogenase_(NAD(+)) Aldehyde dehydrogenase (NAD(+))], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.2.1.3 1.2.1.3] </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=4fqf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4fqf OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4fqf RCSB], [http://www.ebi.ac.uk/pdbsum/4fqf PDBsum]</span></td></tr>
		+	</table>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Aldehyde dehydrogenase-2 (ALDH2) catalyzes the bioactivation of nitroglycerin (glyceryl trinitrate, GTN) in blood vessels, resulting in vasodilation by nitric oxide (NO) or a related species. Because the mechanism of this reaction is still unclear we determined the three-dimensional structures of wild-type (WT) ALDH2 and of a triple mutant of the protein that exhibits low denitration activity (E268Q/C301S/C303S) in complex with GTN. The structure of the triple mutant showed that GTN binds to the active site via polar contacts to the oxyanion hole and to residues 268 and 301 as well as by van der Waals interactions to hydrophobic residues of the catalytic pocket. The structure of the GTN-soaked wild-type protein revealed a thionitrate adduct to Cys-302 as the first reaction intermediate, which was also found by mass spectrometry (MS) experiments. In addition, the MS data identified sulfinic acid as the irreversibly inactivated enzyme species. Assuming that the structures of the triple mutant and wild-type ALDH2 reflect binding of GTN to the catalytic site and the first reaction step, respectively, superposition of the two structures indicates that denitration of GTN is initiated by nucleophilic attack of Cys-302 at one of the terminal nitrate groups, resulting in formation of the observed thionitrate intermediate and release of 1,2-glyceryl dinitrate. Our results shed light on the molecular mechanism of the GTN denitration reaction and provide useful information on the structural requirements for high affinity binding of organic nitrates to the catalytic site of ALDH2.

-	~~{{STRUCTURE_4fqf\| PDB=4fqf \| SCENE= }}~~	+	Vascular Bioactivation of Nitroglycerin by Aldehyde Dehydrogenase-2: REACTION INTERMEDIATES REVEALED BY CRYSTALLOGRAPHY AND MASS SPECTROMETRY.,Lang BS, Gorren AC, Oberdorfer G, Wenzl MV, Furdui CM, Poole LB, Mayer B, Gruber K J Biol Chem. 2012 Nov 2;287(45):38124-34. doi: 10.1074/jbc.M112.371716. Epub 2012, Sep 17. PMID:22988236<ref>PMID:22988236</ref>

-	~~===Crystal structure of~~ a ~~thionitrate intermediate~~ of ~~human aldehyde dehydrogenase-2===~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>

-	~~{{ABSTRACT_PUBMED_22988236}}~~	+	==See Also==
-		+	*[[Aldehyde dehydrogenase\|Aldehyde dehydrogenase]]
-	==~~About this Structure~~==	+	== References ==
-	[[~~4fqf~~]] ~~is a 4 chain structure with sequence from [http:~~//~~en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4FQF OCA].~~	+	<references/>
		+	__TOC__
		+	</StructureSection>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
-	[[Category: Gruber, K.]]	+	[[Category: Gruber, K]]
-	[[Category: Lang, B S.]]	+	[[Category: Lang, B S]]
	[[Category: Aldehyde]]		[[Category: Aldehyde]]
	[[Category: Ester]]		[[Category: Ester]]

OCA at 09:37, 21 November 2012

2012-11-21T09:37:38Z

←Older revision		Revision as of 09:37, 21 November 2012
Line 1:		Line 1:
-	[[Image:4fqf.~~jpg~~\|left\|200px]]	+	[[Image:4fqf.png\|left\|200px]]

	{{STRUCTURE_4fqf\| PDB=4fqf \| SCENE= }}		{{STRUCTURE_4fqf\| PDB=4fqf \| SCENE= }}
Line 5:		Line 5:
	===Crystal structure of a thionitrate intermediate of human aldehyde dehydrogenase-2===		===Crystal structure of a thionitrate intermediate of human aldehyde dehydrogenase-2===

		+	{{ABSTRACT_PUBMED_22988236}}

	==About this Structure==		==About this Structure==

OCA at 20:49, 26 September 2012

2012-09-26T20:49:29Z

←Older revision		Revision as of 20:49, 26 September 2012
Line 1:		Line 1:
-	~~'''Unreleased structure'''~~	+	[[Image:4fqf.jpg\|left\|200px]]

-	~~The entry~~ 4fqf ~~is ON HOLD~~ ~~until Paper Publication~~	+	{{STRUCTURE_4fqf\| PDB=4fqf \| SCENE= }}

-	~~Authors: Lang, B.S., Gruber, K.~~	+	===Crystal structure of a thionitrate intermediate of human aldehyde dehydrogenase-2===

-	~~Description: Crystal structure of~~ a ~~thionitrate intermediate of human aldehyde dehydrogenase~~-2	+
		+	==About this Structure==
		+	[[4fqf]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4FQF OCA].
		+	[[Category: Homo sapiens]]
		+	[[Category: Gruber, K.]]
		+	[[Category: Lang, B S.]]
		+	[[Category: Aldehyde]]
		+	[[Category: Ester]]
		+	[[Category: Nad]]
		+	[[Category: Organic nitrate]]
		+	[[Category: Oxidoreductase]]
		+	[[Category: Oxidoreductase-intermediate complex]]
		+	[[Category: Rossmann fold]]

OCA at 05:02, 18 July 2012

2012-07-18T05:02:31Z

←Older revision		Revision as of 05:02, 18 July 2012
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

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

	Authors: Lang, B.S., Gruber, K.		Authors: Lang, B.S., Gruber, K.

	Description: Crystal structure of a thionitrate intermediate of human aldehyde dehydrogenase-2		Description: Crystal structure of a thionitrate intermediate of human aldehyde dehydrogenase-2

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

2012-07-04T07:19:31Z

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

←Older revision

Revision as of 07:19, 4 July 2012

OCA: New page: '''Unreleased structure''' The entry 4fqf is ON HOLD Authors: Lang, B.S., Gruber, K. Description: Crystal structure of a thionitrate intermediate of human aldehyde dehydrogenase-2

2012-07-04T07:19:30Z

New page: '''Unreleased structure''' The entry 4fqf is ON HOLD Authors: Lang, B.S., Gruber, K. Description: Crystal structure of a thionitrate intermediate of human aldehyde dehydrogenase-2

New page

'''Unreleased structure'''

The entry 4fqf is ON HOLD

Authors: Lang, B.S., Gruber, K.

Description: Crystal structure of a thionitrate intermediate of human aldehyde dehydrogenase-2