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(New page: 200px<br /> <applet load="1f0y" size="450" color="white" frame="true" align="right" spinBox="true" caption="1f0y, resolution 1.80Å" /> '''L-3-HYDROXYACYL-COA...) |
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caption="1f0y, resolution 1.80Å" /> | caption="1f0y, resolution 1.80Å" /> | ||
'''L-3-HYDROXYACYL-COA DEHYDROGENASE COMPLEXED WITH ACETOACETYL-COA AND NAD+'''<br /> | '''L-3-HYDROXYACYL-COA DEHYDROGENASE COMPLEXED WITH ACETOACETYL-COA AND NAD+'''<br /> | ||
==Overview== | ==Overview== | ||
| - | l-3-Hydroxyacyl-CoA dehydrogenase reversibly catalyzes the conversion of | + | l-3-Hydroxyacyl-CoA dehydrogenase reversibly catalyzes the conversion of l-3-hydroxyacyl-CoA to 3-ketoacyl-CoA concomitant with the reduction of NAD(+) to NADH as part of the beta-oxidation spiral. In this report, crystal structures have been solved for the apoenzyme, binary complexes of the enzyme with reduced cofactor or 3-hydroxybutyryl-CoA substrate, and an abortive ternary complex of the enzyme with NAD(+) and acetoacetyl-CoA. The models illustrate positioning of cofactor and substrate within the active site of the enzyme. Comparison of these structures with the previous model of the enzyme-NAD(+) complex reveals that although significant shifting of the NAD(+)-binding domain relative to the C-terminal domain occurs in the ternary and substrate-bound complexes, there are few differences between the apoenzyme and cofactor-bound complexes. Analysis of these models clarifies the role of key amino acids implicated in catalysis and highlights additional critical residues. Furthermore, a novel charge transfer complex has been identified in the course of abortive ternary complex formation, and its characterization provides additional insight into aspects of the catalytic mechanism of l-3-hydroxyacyl-CoA dehydrogenase. |
==Disease== | ==Disease== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 1F0Y is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with CAA and NAD as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/3-hydroxyacyl-CoA_dehydrogenase 3-hydroxyacyl-CoA dehydrogenase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.1.1.35 1.1.1.35] Full crystallographic information is available from [http:// | + | 1F0Y is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=CAA:'>CAA</scene> and <scene name='pdbligand=NAD:'>NAD</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/3-hydroxyacyl-CoA_dehydrogenase 3-hydroxyacyl-CoA dehydrogenase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.1.1.35 1.1.1.35] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1F0Y OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: Banaszak, L | + | [[Category: Banaszak, L J.]] |
| - | [[Category: Barycki, J | + | [[Category: Barycki, J J.]] |
| - | [[Category: Brien, L | + | [[Category: Brien, L K.O.]] |
| - | [[Category: Strauss, A | + | [[Category: Strauss, A W.]] |
[[Category: CAA]] | [[Category: CAA]] | ||
[[Category: NAD]] | [[Category: NAD]] | ||
[[Category: abortive ternary complex]] | [[Category: abortive ternary complex]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 12:33:43 2008'' |
Revision as of 10:33, 21 February 2008
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L-3-HYDROXYACYL-COA DEHYDROGENASE COMPLEXED WITH ACETOACETYL-COA AND NAD+
Contents |
Overview
l-3-Hydroxyacyl-CoA dehydrogenase reversibly catalyzes the conversion of l-3-hydroxyacyl-CoA to 3-ketoacyl-CoA concomitant with the reduction of NAD(+) to NADH as part of the beta-oxidation spiral. In this report, crystal structures have been solved for the apoenzyme, binary complexes of the enzyme with reduced cofactor or 3-hydroxybutyryl-CoA substrate, and an abortive ternary complex of the enzyme with NAD(+) and acetoacetyl-CoA. The models illustrate positioning of cofactor and substrate within the active site of the enzyme. Comparison of these structures with the previous model of the enzyme-NAD(+) complex reveals that although significant shifting of the NAD(+)-binding domain relative to the C-terminal domain occurs in the ternary and substrate-bound complexes, there are few differences between the apoenzyme and cofactor-bound complexes. Analysis of these models clarifies the role of key amino acids implicated in catalysis and highlights additional critical residues. Furthermore, a novel charge transfer complex has been identified in the course of abortive ternary complex formation, and its characterization provides additional insight into aspects of the catalytic mechanism of l-3-hydroxyacyl-CoA dehydrogenase.
Disease
Known diseases associated with this structure: 2-methyl-3-hydroxybutyryl-CoA dehydrogenase deficiency OMIM:[300256], 3-hydroxyacyl-CoA dehydrogenase deficiency OMIM:[601609], Hyperinsulinemic hypoglycemia, familial, 4 OMIM:[601609]
About this Structure
1F0Y is a Single protein structure of sequence from Homo sapiens with and as ligands. Active as 3-hydroxyacyl-CoA dehydrogenase, with EC number 1.1.1.35 Full crystallographic information is available from OCA.
Reference
Sequestration of the active site by interdomain shifting. Crystallographic and spectroscopic evidence for distinct conformations of L-3-hydroxyacyl-CoA dehydrogenase., Barycki JJ, O'Brien LK, Strauss AW, Banaszak LJ, J Biol Chem. 2000 Sep 1;275(35):27186-96. PMID:10840044
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