|Gene:||fadH||Accession Numbers: G36 (MetaCyc), b3081, ECK3071|
Species: Escherichia coli K-12 substr. MG1655
2,4-Dienoyl-CoA reductase functions in the reductive removal of double bonds extending from even-numbered carbon atoms in unsaturated and polyunsaturated fatty acids.
The product of the reaction catalyzed by E. coli FadH is 2-trans-enoyl-CoA, in contrast with the bovine enzyme, which produces 3-trans-enoyl-CoA. FadH is able to catalyze the reduction of 2-trans,4-cis and 2-trans,4-trans isomers with almost equal efficiency [Dommes84]. This is not due to a cis-trans isomerase activity of the enzyme [Liang00]. Kinetic data first suggested that the reaction proceeds via a ping-pong mechanism [He97]. A crystal structure of the enzyme has been solved at 2.2 Å resolution. A possible electron transfer pathway from the electron source, NADPH, via FAD, the 4Fe-4S cluster, and FMN was proposed, and the authors conclude that a ping-pong kinetic mechanism is unlikely [Hubbard03]. Site-directed mutagenesis was used to identify residues involved in catalysis and to support the proposed reaction mechanism [Tu08].
Expression is induced by growth on oleate and is subject to catabolite repression [Dommes84, You89]. Regulation of fadH expression was later shown to be complex and involves three independent regulators, FadR, ArcA, and cAMP-CRP [Feng10, Feng12a] as well as HipB [Lin13].
|Map Position: [3,229,687 -> 3,231,705]|
Molecular Weight of Polypeptide: 72.678 kD (from nucleotide sequence), 73.0 kD (experimental) [Dommes84 ]
pI: 6.55 [He97]
Unification Links: ASAP:ABE-0010124 , DIP:DIP-9562N , EchoBASE:EB2582 , EcoGene:EG12723 , EcoliWiki:b3081 , ModBase:P42593 , OU-Microarray:b3081 , PortEco:fadH , PR:PRO_000022570 , Pride:P42593 , Protein Model Portal:P42593 , RefSeq:NP_417552 , RegulonDB:G36 , SMR:P42593 , String:511145.b3081 , UniProt:P42593
Relationship Links: InterPro:IN-FAMILY:IPR001155 , InterPro:IN-FAMILY:IPR013027 , InterPro:IN-FAMILY:IPR013785 , InterPro:IN-FAMILY:IPR023753 , PDB:Structure:1PS9 , Pfam:IN-FAMILY:PF00724 , Pfam:IN-FAMILY:PF07992 , Prints:IN-FAMILY:PR00368
|Biological Process:||GO:0033543 - fatty acid beta-oxidation, unsaturated, even number, reductase/isomerase pathway
GO:0055114 - oxidation-reduction process [UniProtGOA11a, GOA01a]
|Molecular Function:||GO:0008670 - 2,4-dienoyl-CoA reductase (NADPH) activity
[GOA01, You89, Dommes84]
GO:0010181 - FMN binding [GOA01a, Liang00]
GO:0051539 - 4 iron, 4 sulfur cluster binding [UniProtGOA11a, Liang00]
GO:0071949 - FAD binding [Dommes84]
GO:0003824 - catalytic activity [GOA01a]
GO:0016491 - oxidoreductase activity [UniProtGOA11a, GOA01a]
GO:0046872 - metal ion binding [UniProtGOA11a]
GO:0051536 - iron-sulfur cluster binding [UniProtGOA11a]
|Cellular Component:||GO:0005829 - cytosol [DiazMejia09]|
|MultiFun Terms:||metabolism → biosynthesis of building blocks → fatty acids and phosphatidic acid|
|metabolism → carbon utilization → fatty acids|
Enzymatic reaction of: 2,4-dienoyl-CoA reductase
Synonyms: 2,4-dienoyl-CoA reductase (NADPH), 4-enoyl-CoA reductase (NADPH), trans-2,3-didehydroacyl-CoA:NADP+ 4-oxidoreductase, DCR
The reaction direction shown, that is, A + B ↔ C + D versus C + D ↔ A + B, is in accordance with the direction of enzyme catalysis.
The reaction is physiologically favored in the direction shown.
The enzyme is inhibited by both substrate and NADPH at higher concentrations [Dommes84].
Primary Physiological Regulators of Enzyme Activity: NADH
|Chain||2 -> 672|
4/2/1999 (pkarp) Merged genes G7600/b3081 and G36/fadH
Markus Krummenacker on Tue Oct 14, 1997:
Gene object created from Blattner lab Genbank (v. M52) entry.
DiazMejia09: Diaz-Mejia JJ, Babu M, Emili A (2009). "Computational and experimental approaches to chart the Escherichia coli cell-envelope-associated proteome and interactome." FEMS Microbiol Rev 33(1);66-97. PMID: 19054114
Dommes82: Dommes V, Luster W, Cvetanovic M, Kunau WH (1982). "Purification by affinity chromatography of 2,4-dienoyl-CoA reductases from bovine liver and Escherichia coli." Eur J Biochem 125(2);335-41. PMID: 6749495
He97: He XY, Yang SY, Schulz H (1997). "Cloning and expression of the fadH gene and characterization of the gene product 2,4-dienoyl coenzyme A reductase from Escherichia coli." Eur J Biochem 1997;248(2);516-20. PMID: 9346310
Kimura04: Kimura C, Mizugaki M, Yamanaka H, Fujino M, Morishima T (2004). "[2,4-Dienoyl-CoA reductases: from discovery toward pathophysiological significance]." Nihon Rinsho 62(8);1577-83. PMID: 15344554
Liang00: Liang X, Thorpe C, Schulz H (2000). "2,4-Dienoyl-CoA reductase from Escherichia coli is a novel iron-sulfur flavoprotein that functions in fatty acid beta-oxidation." Arch Biochem Biophys 2000;380(2);373-9. PMID: 10933894
Lin13: Lin CY, Awano N, Masuda H, Park JH, Inouye M (2013). "Transcriptional repressor HipB regulates the multiple promoters in Escherichia coli." J Mol Microbiol Biotechnol 23(6);440-7. PMID: 24089053
Mizugaki82: Mizugaki M, Nishimaki T, Yamamoto H, Nishimura S, Sagi M, Yamanaka H (1982). "Studies on the metabolism of unsaturated fatty acids. VIII. Induction of 2,4-dienoyl-CoA reductase in Escherichia coli on the addition of unsaturated fatty acids." J Biochem 91(4);1453-6. PMID: 7047514
Mizugaki82a: Mizugaki M, Kimura C, Nishimaki T, Yamamoto H, Sagi M, Nishimura S, Yamanaka H (1982). "Studies on the metabolism of unsaturated fatty acids. X. Purification and some properties of 2,4-dienoyl-CoA reductase from Escherichia coli." J Biochem 92(5);1671-4. PMID: 6759505
Mizugaki83: Mizugaki M, Kimura C, Nishimaki T, Kawaguchi A, Okuda S, Yamanaka H (1983). "Studies on the metabolism of unsaturated fatty acids. XII. Reaction catalyzed by 2,4-dienoyl-CoA reductase of Escherichia coli." J Biochem 94(2);409-13. PMID: 6355075
Tu08: Tu X, Hubbard PA, Kim JJ, Schulz H (2008). "Two distinct proton donors at the active site of Escherichia coli 2,4-dienoyl-CoA reductase are responsible for the formation of different products." Biochemistry 47(4);1167-75. PMID: 18171025
You89: You SY, Cosloy S, Schulz H (1989). "Evidence for the essential function of 2,4-dienoyl-coenzyme A reductase in the beta-oxidation of unsaturated fatty acids in vivo. Isolation and characterization of an Escherichia coli mutant with a defective 2,4-dienoyl-coenzyme A reductase." J Biol Chem 1989;264(28);16489-95. PMID: 2506179
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