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| [[Image:1o02.gif|left|200px]] | | {{Seed}} |
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| {{STRUCTURE_1o02| PDB=1o02 | SCENE= }} | | {{STRUCTURE_1o02| PDB=1o02 | SCENE= }} |
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| '''Human mitochondrial aldehyde dehydrogenase complexed with NADH in the presence of Mg2+'''
| | ===Human mitochondrial aldehyde dehydrogenase complexed with NADH in the presence of Mg2+=== |
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| ==Overview==
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| Crystal 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.
| | The line below this paragraph, {{ABSTRACT_PUBMED_12795606}}, adds the Publication Abstract to the page |
| | (as it appears on PubMed at http://www.pubmed.gov), where 12795606 is the PubMed ID number. |
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| | {{ABSTRACT_PUBMED_12795606}} |
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| ==About this Structure== | | ==About this Structure== |
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| [[Category: Nad]] | | [[Category: Nad]] |
| [[Category: Nadh]] | | [[Category: Nadh]] |
| ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 03:11:53 2008'' | | |
| | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jul 28 11:45:04 2008'' |