1o04: Difference between revisions
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|PDB= 1o04 |SIZE=350|CAPTION= <scene name='initialview01'>1o04</scene>, resolution 1.42Å | |PDB= 1o04 |SIZE=350|CAPTION= <scene name='initialview01'>1o04</scene>, resolution 1.42Å | ||
|SITE= | |SITE= | ||
|LIGAND= <scene name='pdbligand= | |LIGAND= <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> | ||
|ACTIVITY= [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] | |ACTIVITY= <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> | ||
|GENE= ALDH2 OR ALDM ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | |GENE= ALDH2 OR ALDM ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | ||
|DOMAIN= | |||
|RELATEDENTRY=[[1cw3|1CW3]], [[1ag8|1AG8]], [[1a4z|1A4Z]], [[1nzw|1NZW]], [[1nzx|1NZX]], [[1nzz|1NZZ]], [[1o00|1O00]], [[1o01|1O01]], [[1o02|1O02]], [[1o05|1O05]] | |||
|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1o04 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1o04 OCA], [http://www.ebi.ac.uk/pdbsum/1o04 PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1o04 RCSB]</span> | |||
}} | }} | ||
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==Overview== | ==Overview== | ||
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. | 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. | ||
==About this Structure== | ==About this Structure== | ||
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[[Category: Hurley, T D.]] | [[Category: Hurley, T D.]] | ||
[[Category: Perez-Miller, S J.]] | [[Category: Perez-Miller, S J.]] | ||
[[Category: aldh]] | [[Category: aldh]] | ||
[[Category: isomerization]] | [[Category: isomerization]] | ||
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[[Category: nadh]] | [[Category: nadh]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 22:37:54 2008'' | ||
Revision as of 22:37, 30 March 2008
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| , resolution 1.42Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | , , , , | ||||||
| Gene: | ALDH2 OR ALDM (Homo sapiens) | ||||||
| Activity: | Aldehyde dehydrogenase (NAD(+)), with EC number 1.2.1.3 | ||||||
| Related: | 1CW3, 1AG8, 1A4Z, 1NZW, 1NZX, 1NZZ, 1O00, 1O01, 1O02, 1O05
| ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Cys302Ser mutant of human mitochondrial aldehyde dehydrogenase complexed with NAD+ and Mg2+
OverviewOverview
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.
About this StructureAbout this Structure
1O04 is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
ReferenceReference
Coenzyme isomerization is integral to catalysis in aldehyde dehydrogenase., Perez-Miller SJ, Hurley TD, Biochemistry. 2003 Jun 17;42(23):7100-9. PMID:12795606
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