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4fr8

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==Crystal structure of human aldehyde dehydrogenase-2 in complex with nitroglycerin==
==Crystal structure of human aldehyde dehydrogenase-2 in complex with nitroglycerin==
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<StructureSection load='4fr8' size='340' side='right' caption='[[4fr8]], [[Resolution|resolution]] 2.20&Aring;' scene=''>
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<StructureSection load='4fr8' size='340' side='right'caption='[[4fr8]], [[Resolution|resolution]] 2.20&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
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<table><tr><td colspan='2'>[[4fr8]] is a 8 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=4FR8 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4FR8 FirstGlance]. <br>
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<table><tr><td colspan='2'>[[4fr8]] is a 8 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=4FR8 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4FR8 FirstGlance]. <br>
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</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ADP:ADENOSINE-5-DIPHOSPHATE'>ADP</scene>, <scene name='pdbligand=BTB:2-[BIS-(2-HYDROXY-ETHYL)-AMINO]-2-HYDROXYMETHYL-PROPANE-1,3-DIOL'>BTB</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=TNG:PROPANE-1,2,3-TRIYL+TRINITRATE'>TNG</scene>, <scene name='pdbligand=URE:UREA'>URE</scene></td></tr>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.2&#8491;</td></tr>
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<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>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ADP:ADENOSINE-5-DIPHOSPHATE'>ADP</scene>, <scene name='pdbligand=BTB:2-[BIS-(2-HYDROXY-ETHYL)-AMINO]-2-HYDROXYMETHYL-PROPANE-1,3-DIOL'>BTB</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=TNG:PROPANE-1,2,3-TRIYL+TRINITRATE'>TNG</scene>, <scene name='pdbligand=URE:UREA'>URE</scene></td></tr>
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<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>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4fr8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4fr8 OCA], [https://pdbe.org/4fr8 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4fr8 RCSB], [https://www.ebi.ac.uk/pdbsum/4fr8 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4fr8 ProSAT]</span></td></tr>
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<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>
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<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=4fr8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4fr8 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4fr8 RCSB], [http://www.ebi.ac.uk/pdbsum/4fr8 PDBsum]</span></td></tr>
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</table>
</table>
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<div style="background-color:#fffaf0;">
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== Function ==
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== Publication Abstract from PubMed ==
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[https://www.uniprot.org/uniprot/ALDH2_HUMAN ALDH2_HUMAN]
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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.
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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>
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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==See Also==
==See Also==
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*[[Aldehyde dehydrogenase|Aldehyde dehydrogenase]]
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*[[Aldehyde dehydrogenase 3D structures|Aldehyde dehydrogenase 3D structures]]
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== References ==
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<references/>
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__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Gruber, K]]
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[[Category: Large Structures]]
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[[Category: Lang, B S]]
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[[Category: Gruber K]]
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[[Category: Oxidoreductase]]
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[[Category: Lang BS]]
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[[Category: Oxidoreductase-oxidoreductase inhibitor complex]]
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[[Category: Rossmann fold]]
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Current revision

Crystal structure of human aldehyde dehydrogenase-2 in complex with nitroglycerin

PDB ID 4fr8

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