1w6u
From Proteopedia
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| - | | | + | {{STRUCTURE_1w6u| PDB=1w6u | SCENE= }} |
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'''STRUCTURE OF HUMAN DECR TERNARY COMPLEX''' | '''STRUCTURE OF HUMAN DECR TERNARY COMPLEX''' | ||
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==Reference== | ==Reference== | ||
Structure and reactivity of human mitochondrial 2,4-dienoyl-CoA reductase: enzyme-ligand interactions in a distinctive short-chain reductase active site., Alphey MS, Yu W, Byres E, Li D, Hunter WN, J Biol Chem. 2005 Jan 28;280(4):3068-77. Epub 2004 Nov 6. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/15531764 15531764] | Structure and reactivity of human mitochondrial 2,4-dienoyl-CoA reductase: enzyme-ligand interactions in a distinctive short-chain reductase active site., Alphey MS, Yu W, Byres E, Li D, Hunter WN, J Biol Chem. 2005 Jan 28;280(4):3068-77. Epub 2004 Nov 6. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/15531764 15531764] | ||
| - | [[Category: 2,4-dienoyl-CoA reductase (NADPH)]] | ||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
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[[Category: Hunter, W N.]] | [[Category: Hunter, W N.]] | ||
[[Category: Li, D.]] | [[Category: Li, D.]] | ||
| - | [[Category: | + | [[Category: Beta-oxidation]] |
| - | [[Category: | + | [[Category: Dienoyl coa-reductase]] |
| - | [[Category: | + | [[Category: Nadp]] |
| - | [[Category: | + | [[Category: Oxidoreductase]] |
| - | [[Category: | + | [[Category: Reductase]] |
| - | [[Category: | + | [[Category: Short chain dehydrogenase]] |
| - | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 13:14:14 2008'' | |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | |
Revision as of 10:14, 3 May 2008
STRUCTURE OF HUMAN DECR TERNARY COMPLEX
Overview
Fatty acid catabolism by beta-oxidation mainly occurs in mitochondria and to a lesser degree in peroxisomes. Poly-unsaturated fatty acids are problematic for beta-oxidation, because the enzymes directly involved are unable to process all the different double bond conformations and combinations that occur naturally. In mammals, three accessory proteins circumvent this problem by catalyzing specific isomerization and reduction reactions. Central to this process is the NADPH-dependent 2,4-dienoyl-CoA reductase. We present high resolution crystal structures of human mitochondrial 2,4-dienoyl-CoA reductase in binary complex with cofactor, and the ternary complex with NADP(+) and substrate trans-2,trans-4-dienoyl-CoA at 2.1 and 1.75 A resolution, respectively. The enzyme, a homotetramer, is a short-chain dehydrogenase/reductase with a distinctive catalytic center. Close structural similarity between the binary and ternary complexes suggests an absence of large conformational changes during binding and processing of substrate. The site of catalysis is relatively open and placed beside a flexible loop thereby allowing the enzyme to accommodate and process a wide range of fatty acids. Seven single mutants were constructed, by site-directed mutagenesis, to investigate the function of selected residues in the active site thought likely to either contribute to the architecture of the active site or to catalysis. The mutant proteins were overexpressed, purified to homogeneity, and then characterized. The structural and kinetic data are consistent and support a mechanism that derives one reducing equivalent from the cofactor, and one from solvent. Key to the acquisition of a solvent-derived proton is the orientation of substrate and stabilization of a dienolate intermediate by Tyr-199, Asn-148, and the oxidized nicotinamide.
About this Structure
1W6U is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Structure and reactivity of human mitochondrial 2,4-dienoyl-CoA reductase: enzyme-ligand interactions in a distinctive short-chain reductase active site., Alphey MS, Yu W, Byres E, Li D, Hunter WN, J Biol Chem. 2005 Jan 28;280(4):3068-77. Epub 2004 Nov 6. PMID:15531764 Page seeded by OCA on Sat May 3 13:14:14 2008
