1w73
From Proteopedia
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| - | [[Image:1w73.gif|left|200px]] | + | [[Image:1w73.gif|left|200px]] |
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| - | '''BINARY STRUCTURE OF HUMAN DECR SOLVED BY SEMET SAD.''' | + | {{Structure |
| + | |PDB= 1w73 |SIZE=350|CAPTION= <scene name='initialview01'>1w73</scene>, resolution 2.100Å | ||
| + | |SITE= <scene name='pdbsite=1:Nap+Binding+Site+For+Chain+D'>1</scene> | ||
| + | |LIGAND= <scene name='pdbligand=NAP:NADP+NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NAP</scene> and <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene> | ||
| + | |ACTIVITY= [http://en.wikipedia.org/wiki/2,4-dienoyl-CoA_reductase_(NADPH) 2,4-dienoyl-CoA reductase (NADPH)], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.3.1.34 1.3.1.34] | ||
| + | |GENE= | ||
| + | }} | ||
| + | |||
| + | '''BINARY STRUCTURE OF HUMAN DECR SOLVED BY SEMET SAD.''' | ||
| + | |||
==Overview== | ==Overview== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 1W73 is a [ | + | 1W73 is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1W73 OCA]. |
==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:// | + | 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: 2,4-dienoyl-CoA reductase (NADPH)]] | ||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
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[[Category: short chain dehydrogenase]] | [[Category: short chain dehydrogenase]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 14:53:05 2008'' |
Revision as of 12:53, 20 March 2008
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| , resolution 2.100Å | |||||||
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| Sites: | |||||||
| Ligands: | and | ||||||
| Activity: | 2,4-dienoyl-CoA reductase (NADPH), with EC number 1.3.1.34 | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
BINARY STRUCTURE OF HUMAN DECR SOLVED BY SEMET SAD.
Contents |
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.
Disease
Known diseases associated with this structure: DECR deficiency (2) OMIM:[222745]
About this Structure
1W73 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
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