Metabolic Modeling Tutorial
discounted EARLY registration ends Dec 31, 2014
BioCyc websites down
12/28 - 12/31
for maintenance.
Metabolic Modeling Tutorial
discounted EARLY registration ends Dec 31, 2014
BioCyc websites down
12/28 - 12/31
for maintenance.
Metabolic Modeling Tutorial
discounted EARLY registration ends Dec 31, 2014
BioCyc websites down
12/28 - 12/31
for maintenance.
Metabolic Modeling Tutorial
discounted EARLY registration ends Dec 31, 2014
BioCyc websites down
12/28 - 12/31
for maintenance.
Metabolic Modeling Tutorial
discounted EARLY registration ends Dec 31, 2014
BioCyc websites down
12/28 - 12/31
for maintenance.
twitter

MetaCyc Enzyme: fatty acyl-CoA synthetase

Gene: fadD Accession Numbers: EG11530 (MetaCyc), b1805, ECK1803

Synonyms: oldD

Species: Escherichia coli K-12 substr. MG1655

Subunit composition of fatty acyl-CoA synthetase = [FadD]2

Summary:
Long chain fatty acid CoA-ligase, also known as acyl-CoA synthetase or synthase, plays a pivotal role in the transport and activation of exogenous fatty acids prior to their subsequent degradation or incorporation into phospholipids. This is the rate limiting step of β-oxidation in E. coli [Kameda81]. The enzyme catalyzes the esterification of fatty acids into metabolically active CoA thioesters concomitant with transport. The reaction proceeds by a two-step mechanism. The enzyme has broad chain length specificity, with maximal activities associated with fatty acids ranging in length between C-12 and C-18. The enzyme appears to be partially membrane-associated [Black92].

Long chain fatty acid uptake into inner membrane vesicles is dependent on the level of FadD in the vesicles [Schmelter04]. Import of labelled oleate is abolished in fadD null strains [Weimar02]. Specific mutations in fadD that abolish or reduce the formation of fatty acyl-CoA likewise abolish or reduce the import of exogenous long chain fatty acids [Weimar02]. It has been suggested that FadD specifically associates with the inner membrane in response to the presence of long chain fatty acids [Weimar02].

Review: [Dirusso04]

Locations [Comment 1]: inner membrane, cytosol

Map Position: [1,886,085 <- 1,887,770]

Molecular Weight of Polypeptide: 62.332 kD (from nucleotide sequence), 62 kD (experimental) [Black92 ]

pI: 6.61

Unification Links: ASAP:ABE-0006005 , CGSC:792 , EchoBASE:EB1492 , EcoGene:EG11530 , EcoliWiki:b1805 , ModBase:P69451 , OU-Microarray:b1805 , PortEco:fadD , PR:PRO_000022568 , Pride:P69451 , Protein Model Portal:P69451 , RefSeq:NP_416319 , RegulonDB:EG11530 , SMR:P69451 , String:511145.b1805 , UniProt:P69451

Relationship Links: InterPro:IN-FAMILY:IPR000873 , InterPro:IN-FAMILY:IPR020845 , InterPro:IN-FAMILY:IPR025110 , Pfam:IN-FAMILY:PF00501 , Pfam:IN-FAMILY:PF13193 , Prosite:IN-FAMILY:PS00455

Gene-Reaction Schematic: ?

Instance reactions of [a 2,3,4-saturated fatty acid + ATP + coenzyme A → a 2,3,4-saturated fatty acyl CoA + AMP + diphosphate] (6.2.1.3):
i1: phytanate + ATP + coenzyme A → phytanoyl-CoA + AMP + diphosphate (6.2.1.24)

i2: octanoate + ATP + coenzyme A → octanoyl-CoA + AMP + diphosphate (6.2.1.3)

i3: decanoate + ATP + coenzyme A → decanoyl-CoA + AMP + diphosphate (6.2.1.3)

i4: hexanoate + ATP + coenzyme A → hexanoyl-CoA + AMP + diphosphate (6.2.1.-)

i5: palmitate + ATP + coenzyme A → palmitoyl-CoA + AMP + diphosphate (6.2.1.3)

i6: pristanate + ATP + coenzyme A → pristanoyl-CoA + AMP + diphosphate (6.2.1.3)

GO Terms:

Biological Process: GO:0001676 - long-chain fatty acid metabolic process Inferred by computational analysis Inferred from experiment [Black97, Kameda81, Black92, GOA01]
GO:0006629 - lipid metabolic process Inferred from experiment Inferred by computational analysis [UniProtGOA11a, Hsu91a]
GO:0006631 - fatty acid metabolic process Inferred from experiment Inferred by computational analysis [UniProtGOA11a, Hsu91a]
GO:0006635 - fatty acid beta-oxidation Inferred from experiment [Kameda81]
GO:0006637 - acyl-CoA metabolic process Inferred from experiment [Kameda81]
GO:0008654 - phospholipid biosynthetic process Inferred from experiment [Hsu91a]
GO:0008152 - metabolic process Inferred by computational analysis [GOA01a]
Molecular Function: GO:0004467 - long-chain fatty acid-CoA ligase activity Inferred from experiment Inferred by computational analysis [GOA01, Black97, Black92, Kameda81]
GO:0005504 - fatty acid binding Inferred from experiment [Black97]
GO:0070538 - oleic acid binding Inferred from experiment [Black97]
GO:0000166 - nucleotide binding Inferred by computational analysis [UniProtGOA11a]
GO:0003824 - catalytic activity Inferred by computational analysis [GOA01a]
GO:0005524 - ATP binding Inferred by computational analysis [UniProtGOA11a]
GO:0016874 - ligase activity Inferred by computational analysis [UniProtGOA11a]
Cellular Component: GO:0005737 - cytoplasm Inferred from experiment [Black97]
GO:0005829 - cytosol Author statement Inferred by computational analysis [DiazMejia09, Weimar02]
GO:0009898 - cytoplasmic side of plasma membrane Author statement [Weimar02]
GO:0016020 - membrane Inferred by computational analysis [UniProtGOA11, UniProtGOA11a]

MultiFun Terms: metabolism biosynthesis of macromolecules (cellular constituents) phospholipid
metabolism carbon utilization fatty acids

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


Enzymatic reaction of: fatty acyl-CoA synthetase

Synonyms: long chain fatty acid CoA-ligase, acyl-activating enzyme, acyl-CoA synthase, fatty acid thiokinase (long-chain), lignoceroyl-CoA synthase, long-chain acyl-CoA synthetase, palmitoyl-CoA synthase, arachidonyl-CoA synthetase, acid:CoA ligase (AMP forming)

a 2,3,4-saturated fatty acid + ATP + coenzyme A <=> a 2,3,4-saturated fatty acyl CoA + AMP + diphosphate

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 [Comment 2]:

In Pathways: fatty acid β-oxidation I

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

Cofactors or Prosthetic Groups: Mg2+

Inhibitors (Unknown Mechanism): perchlorate , thiocyanate

Kinetic Parameters:

Substrate
Km (μM)
kcat (sec-1)
kcat/Km (sec-1 μM-1)
Citations
ATP
33.0
[Kameda81, BRENDA14]
ATP
25.0, 50.0
[Kameda85a, BRENDA14]
ATP
0.029
[Weimar02, BRENDA14]
coenzyme A
34.0, 35.0, 53.0
[Kameda85a, BRENDA14]

pH(opt): 7.8 [BRENDA14, Kameda85a], 8.1 [BRENDA14, Kameda85a], 8.5 [BRENDA14, Kameda85a]


Sequence Features

Feature Class Location Citations Comment
Sequence-Conflict 34 -> 51
[Black92, UniProt10a]
Alternate sequence: GALRRSTCVCEYGGGNDL; UniProt: (in Ref. 2; AAA23752);
Mutagenesis-Variant 213
[Weimar02, UniProt11]
Alternate sequence: A; UniProt: Loss of activity.
Nucleotide-Phosphate-Binding-Region 213 -> 224
[UniProt10]
UniProt: ATP; Non-Experimental Qualifier: probably;
Mutagenesis-Variant 214
[Weimar02, UniProt11]
Alternate sequence: A; UniProt: 10% of wild-type activity.
Mutagenesis-Variant 216
[Weimar02, UniProt11]
Alternate sequence: A; UniProt: Decreases activity.
Mutagenesis-Variant 217
[Weimar02, UniProt11]
Alternate sequence: A; UniProt: Decreases activity.
Mutagenesis-Variant 219
[Weimar02, UniProt11]
Alternate sequence: A; UniProt: Decreases activity.
Mutagenesis-Variant 222
[Weimar02, UniProt11]
Alternate sequence: A; UniProt: Decreases activity.
Mutagenesis-Variant 361
[Weimar02, UniProt11]
Alternate sequence: A; UniProt: Loss of activity.
Sequence-Conflict 468 -> 490
[Black92, UniProt10a]
Alternate sequence: TRLKMSSCSMVAYRKSRLLAYLP; UniProt: (in Ref. 2; AAA23752);
Sequence-Conflict 496
[Black92, UniProt10a]
Alternate sequence: G; UniProt: (in Ref. 2; AAA23752);
Sequence-Conflict 555 -> 561
[Black92, UniProt10a]
Alternate sequence: QSGQ; UniProt: (in Ref. 2; AAA23752);

History:
10/20/97 Gene b1805 from Blattner lab Genbank (v. M52) entry merged into EcoCyc gene EG11530; confirmed by SwissProt match.


References

Black92: Black PN, DiRusso CC, Metzger AK, Heimert TL (1992). "Cloning, sequencing, and expression of the fadD gene of Escherichia coli encoding acyl coenzyme A synthetase." J Biol Chem 1992;267(35);25513-20. PMID: 1460045

Black97: Black PN, Zhang Q, Weimar JD, DiRusso CC (1997). "Mutational analysis of a fatty acyl-coenzyme A synthetase signature motif identifies seven amino acid residues that modulate fatty acid substrate specificity." J Biol Chem 272(8);4896-903. PMID: 9030548

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

Dirusso04: Dirusso CC, Black PN (2004). "Bacterial long chain fatty acid transport: gateway to a fatty acid-responsive signaling system." J Biol Chem 279(48);49563-6. PMID: 15347640

GOA01: GOA, MGI (2001). "Gene Ontology annotation based on Enzyme Commission mapping." Genomics 74;121-128.

GOA01a: GOA, DDB, FB, MGI, ZFIN (2001). "Gene Ontology annotation through association of InterPro records with GO terms."

Hsu91a: Hsu L, Jackowski S, Rock CO (1991). "Isolation and characterization of Escherichia coli K-12 mutants lacking both 2-acyl-glycerophosphoethanolamine acyltransferase and acyl-acyl carrier protein synthetase activity." J Biol Chem 1991;266(21);13783-8. PMID: 1649829

Kameda81: Kameda K, Nunn WD (1981). "Purification and characterization of acyl coenzyme A synthetase from Escherichia coli." J Biol Chem 1981;256(11);5702-7. PMID: 7016858

Kameda85: Kameda K, Suzuki LK, Imai Y (1985). "Further purification, characterization and salt activation of acyl-CoA synthetase from Escherichia coli." Biochim Biophys Acta 1985;840(1);29-36. PMID: 3888279

Kameda85a: Kameda K, Imai Y (1985). "Isolation and characterization of the multiple charge isoforms of acyl-CoA synthetase from Escherichia coli." Biochim Biophys Acta 832(3);343-50. PMID: 3907712

Schmelter04: Schmelter T, Trigatti BL, Gerber GE, Mangroo D (2004). "Biochemical demonstration of the involvement of fatty acyl-CoA synthetase in fatty acid translocation across the plasma membrane." J Biol Chem 279(23);24163-70. PMID: 15067008

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

UniProt10a: UniProt Consortium (2010). "UniProt version 2010-11 released on 2010-11-02 00:00:00." Database.

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

UniProtGOA11: UniProt-GOA (2011). "Gene Ontology annotation based on the manual assignment of UniProtKB Subcellular Location terms in UniProtKB/Swiss-Prot entries."

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

Weimar02: Weimar JD, DiRusso CC, Delio R, Black PN (2002). "Functional role of fatty acyl-coenzyme A synthetase in the transmembrane movement and activation of exogenous long-chain fatty acids. Amino acid residues within the ATP/AMP signature motif of Escherichia coli FadD are required for enzyme activity and fatty acid transport." J Biol Chem 277(33);29369-76. PMID: 12034706


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 Sat Dec 20, 2014, biocyc11.