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MetaCyc Enzyme: 2,4-dienoyl-CoA reductase

Gene: fadH Accession Numbers: G36 (MetaCyc), b3081, ECK3071

Synonyms: ygjL

Species: Escherichia coli K-12 substr. MG1655

Summary:
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, Feng12] as well as HipB [Lin13].

Citations: [Mizugaki82, Mizugaki82a, Mizugaki83, Kimura04]

Locations: cytosol

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

Gene-Reaction Schematic: ?

GO Terms:

Biological Process: GO:0033543 - fatty acid beta-oxidation, unsaturated, even number, reductase/isomerase pathway Inferred from experiment [You89]
GO:0055114 - oxidation-reduction process Inferred by computational analysis [UniProtGOA11a, GOA01]
Molecular Function: GO:0008670 - 2,4-dienoyl-CoA reductase (NADPH) activity Inferred from experiment Inferred by computational analysis [GOA01a, You89, Dommes84]
GO:0010181 - FMN binding Inferred from experiment Inferred by computational analysis [GOA01, Liang00]
GO:0051539 - 4 iron, 4 sulfur cluster binding Inferred from experiment Inferred by computational analysis [UniProtGOA11a, Liang00]
GO:0071949 - FAD binding Inferred from experiment [Dommes84]
GO:0003824 - catalytic activity Inferred by computational analysis [GOA01]
GO:0016491 - oxidoreductase activity Inferred by computational analysis [UniProtGOA11a, GOA01]
GO:0046872 - metal ion binding Inferred by computational analysis [UniProtGOA11a]
GO:0051536 - iron-sulfur cluster binding Inferred by computational analysis [UniProtGOA11a]
Cellular Component: GO:0005829 - cytosol Inferred by computational analysis [DiazMejia09]

MultiFun Terms: metabolism biosynthesis of building blocks fatty acids and phosphatidic acid
metabolism carbon utilization fatty acids

Credits:
Imported from EcoCyc 16-Sep-2014 by Paley S , SRI International


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

trans-Δ2, cis-Δ4-decadienoyl-CoA + NADPH + H+ <=> trans-Δ2-decenoyl-CoA + NADP+

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.

Alternative Substrates for trans-Δ2, cis-Δ4-decadienoyl-CoA [Comment 1 ]: trans,trans-2,4-decadienoyl-CoA [Dommes84 , Dommes82 ]

Credits:
Imported from EcoCyc 16-Sep-2014 by Paley S , SRI International

Summary:
The enzyme is inhibited by both substrate and NADPH at higher concentrations [Dommes84].

Cofactors or Prosthetic Groups: a [4Fe-4S] iron-sulfur cluster [Comment 2, Liang00], FMN [Comment 3, Liang00], FAD [Comment 4, Dommes84]

Inhibitors (Competitive): trans-Δ2, cis-Δ4-decadienoyl-CoA [Dommes84]

Inhibitors (Noncompetitive): NADH [Dommes84]

Inhibitors (Unknown Mechanism): p-chloromercuribenzoate [Dommes84]

Primary Physiological Regulators of Enzyme Activity: NADH

Kinetic Parameters:

Substrate
Km (μM)
kcat (sec-1)
kcat/Km (sec-1 μM-1)
Citations
trans,trans-2,4-decadienoyl-CoA
2.3
16.0
[He97]
NADPH
50.0
[He97, BRENDA14]
NADPH
0.8
9.5
[Tu08, BRENDA14]

pH(opt): 7.4 [BRENDA14, Mizugaki82]


Sequence Features

Feature Class Location Citations Comment
Cleavage-of-Initial-Methionine 1
[He97, UniProt11]
UniProt: Removed.
Chain 2 -> 672
[UniProt09]
UniProt: 2,4-dienoyl-CoA reductase [NADPH];
Metal-Binding-Site 335
[UniProt10]
UniProt: Iron-sulfur (4Fe-4S); Non-Experimental Qualifier: by similarity;
Metal-Binding-Site 338
[UniProt10]
UniProt: Iron-sulfur (4Fe-4S); Non-Experimental Qualifier: by similarity;
Metal-Binding-Site 342
[UniProt10]
UniProt: Iron-sulfur (4Fe-4S); Non-Experimental Qualifier: by similarity;
Metal-Binding-Site 354
[UniProt10]
UniProt: Iron-sulfur (4Fe-4S); Non-Experimental Qualifier: by similarity;
Acetylation-Modification 564
[Yu08]
 

History:
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.


References

BRENDA14: BRENDA team (2014). "Imported from BRENDA version existing on Aug 2014." http://www.brenda-enzymes.org.

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

Dommes84: Dommes V, Kunau WH (1984). "2,4-Dienoyl coenzyme A reductases from bovine liver and Escherichia coli. Comparison of properties." J Biol Chem 1984;259(3);1781-8. PMID: 6363415

Feng10: Feng Y, Cronan JE (2010). "Overlapping repressor binding sites result in additive regulation of Escherichia coli FadH by FadR and ArcA." J Bacteriol 192(17);4289-99. PMID: 20622065

Feng12: Feng Y, Cronan JE (2012). "Crosstalk of Escherichia coli FadR with global regulators in expression of fatty acid transport genes." PLoS One 7(9);e46275. PMID: 23029459

GOA01: GOA, DDB, FB, MGI, ZFIN (2001). "Gene Ontology annotation through association of InterPro records with GO terms."

GOA01a: GOA, MGI (2001). "Gene Ontology annotation based on Enzyme Commission mapping." Genomics 74;121-128.

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

Hubbard03: Hubbard PA, Liang X, Schulz H, Kim JJ (2003). "The crystal structure and reaction mechanism of Escherichia coli 2,4-dienoyl-CoA reductase." J Biol Chem 278(39);37553-60. PMID: 12840019

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

UniProt09: UniProt Consortium (2009). "UniProt version 15.8 released on 2009-10-01 00:00:00." Database.

UniProt10: UniProt Consortium (2010). "UniProt version 2010-07 released on 2010-06-15 00:00:00." Database.

UniProt11: UniProt Consortium (2011). "UniProt version 2011-06 released on 2011-06-30 00:00:00." Database.

UniProtGOA11a: UniProt-GOA (2011). "Gene Ontology annotation based on manual assignment of UniProtKB keywords in UniProtKB/Swiss-Prot entries."

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

Yu08: Yu BJ, Kim JA, Moon JH, Ryu SE, Pan JG (2008). "The diversity of lysine-acetylated proteins in Escherichia coli." J Microbiol Biotechnol 18(9);1529-36. PMID: 18852508


Report Errors or Provide Feedback
Please cite the following article in publications resulting from the use of MetaCyc: Caspi et al, Nucleic Acids Research 42:D459-D471 2014
Page generated by SRI International Pathway Tools version 18.5 on Mon Nov 24, 2014, BIOCYC13A.