1o04: Difference between revisions
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==Cys302Ser mutant of human mitochondrial aldehyde dehydrogenase complexed with NAD+ and Mg2+== | ==Cys302Ser mutant of human mitochondrial aldehyde dehydrogenase complexed with NAD+ and Mg2+== | ||
<StructureSection load='1o04' size='340' side='right' caption='[[1o04]], [[Resolution|resolution]] 1.42Å' scene=''> | <StructureSection load='1o04' size='340' side='right'caption='[[1o04]], [[Resolution|resolution]] 1.42Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[1o04]] is a 8 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=1O04 OCA]. For a <b>guided tour on the structure components</b> use [http:// | <table><tr><td colspan='2'>[[1o04]] is a 8 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=1O04 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=1O04 FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=GAI:GUANIDINE'>GAI</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></td></tr> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=GAI:GUANIDINE'>GAI</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></td></tr> | ||
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1cw3|1cw3]], [[1ag8|1ag8]], [[1a4z|1a4z]], [[1nzw|1nzw]], [[1nzx|1nzx]], [[1nzz|1nzz]], [[1o00|1o00]], [[1o01|1o01]], [[1o02|1o02]], [[1o05|1o05]]</td></tr> | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1cw3|1cw3]], [[1ag8|1ag8]], [[1a4z|1a4z]], [[1nzw|1nzw]], [[1nzx|1nzx]], [[1nzz|1nzz]], [[1o00|1o00]], [[1o01|1o01]], [[1o02|1o02]], [[1o05|1o05]]</div></td></tr> | ||
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">ALDH2 OR ALDM ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">ALDH2 OR 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:// | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=1o04 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1o04 OCA], [http://pdbe.org/1o04 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1o04 RCSB], [http://www.ebi.ac.uk/pdbsum/1o04 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1o04 ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Evolutionary Conservation == | == Evolutionary Conservation == | ||
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</div> | </div> | ||
<div class="pdbe-citations 1o04" style="background-color:#fffaf0;"></div> | <div class="pdbe-citations 1o04" style="background-color:#fffaf0;"></div> | ||
==See Also== | |||
*[[Aldehyde dehydrogenase 3D structures|Aldehyde dehydrogenase 3D structures]] | |||
== References == | == References == | ||
<references/> | <references/> | ||
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</StructureSection> | </StructureSection> | ||
[[Category: Human]] | [[Category: Human]] | ||
[[Category: Large Structures]] | |||
[[Category: Hurley, T D]] | [[Category: Hurley, T D]] | ||
[[Category: Perez-Miller, S J]] | [[Category: Perez-Miller, S J]] | ||
Revision as of 12:01, 2 December 2020
Cys302Ser mutant of human mitochondrial aldehyde dehydrogenase complexed with NAD+ and Mg2+Cys302Ser mutant of human mitochondrial aldehyde dehydrogenase complexed with NAD+ and Mg2+
Structural highlights
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 PubMedCrystal structures of many enzymes in the aldehyde dehydrogenase superfamily determined in the presence of bound NAD(P)(+) have exhibited conformational flexibility for the nicotinamide half of the cofactor. This has been hypothesized to be important in catalysis because one conformation would block the second half of the reaction, but no firm evidence has been put forth which shows whether the oxidized and reduced cofactors preferentially occupy the two observed conformations. We present here two structures of the wild type and two structures of a Cys302Ser mutant of human mitochondrial aldehyde dehydrogenase in binary complexes with NAD(+) and NADH. These structures, including the Cys302Ser mutant in complex with NAD(+) at 1.4 A resolution and the wild-type enzyme in complex with NADH at 1.9 A resolution, provide strong evidence that bound NAD(+) prefers an extended conformation ideal for hydride transfer and bound NADH prefers a contracted conformation ideal for acyl-enzyme hydrolysis. Unique interactions between the cofactor and the Rossmann fold make isomerization possible while allowing the remainder of the active site complex to remain intact. In addition, these structures clarify the role of magnesium in activating the human class 2 enzyme. Our data suggest that the presence of magnesium may lead to selection of particular conformations and speed isomerization of the reduced cofactor following hydride transfer. Coenzyme isomerization is integral to catalysis in aldehyde dehydrogenase.,Perez-Miller SJ, Hurley TD Biochemistry. 2003 Jun 17;42(23):7100-9. PMID:12795606[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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