1f14
From Proteopedia
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|SITE= | |SITE= | ||
|LIGAND= | |LIGAND= | ||
| - | |ACTIVITY= [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] | + | |ACTIVITY= <span class='plainlinks'>[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] </span> |
|GENE= | |GENE= | ||
| + | |DOMAIN= | ||
| + | |RELATEDENTRY=[[3had|3HAD]], [[1f12|1F12]], [[1f17|1F17]], [[1f0y|1F0Y]] | ||
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1f14 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1f14 OCA], [http://www.ebi.ac.uk/pdbsum/1f14 PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1f14 RCSB]</span> | ||
}} | }} | ||
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==Overview== | ==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. | 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:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=300256 300256]], 3-hydroxyacyl-CoA dehydrogenase deficiency OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=601609 601609]], Hyperinsulinemic hypoglycemia, familial, 4 OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=601609 601609]] | ||
==About this Structure== | ==About this Structure== | ||
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[[Category: l-3-hydroxyacyl-coa (apoenzyme)]] | [[Category: l-3-hydroxyacyl-coa (apoenzyme)]] | ||
| - | ''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 20:13:43 2008'' |
Revision as of 17:13, 30 March 2008
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| , resolution 2.30Å | |||||||
|---|---|---|---|---|---|---|---|
| Activity: | 3-hydroxyacyl-CoA dehydrogenase, with EC number 1.1.1.35 | ||||||
| Related: | 3HAD, 1F12, 1F17, 1F0Y
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| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
L-3-HYDROXYACYL-COA DEHYDROGENASE (APO)
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.
About this Structure
1F14 is a Single protein structure of sequence from Homo sapiens. 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
Page seeded by OCA on Sun Mar 30 20:13:43 2008
