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Escherichia coli K-12 substr. MG1655 Enzyme: biotin carboxylase



Gene: accC Accession Numbers: EG10276 (EcoCyc), b3256, ECK3243

Synonyms: fabG

Regulation Summary Diagram: ?

Component of: acetyl-CoA carboxylase (extended summary available)

Subunit composition of biotin carboxylase = [AccC]2

Summary:
Mutations in the homologous and functionally identical subunit in mammalian proprionyl-CoA carboxylase and 3-methylcrotonyl-CoA carboxylase result in the metabolic deficiency diseases of propionic acidemia or methylcrotonylglycinuria. Kinetic analysis of mutants analogous to the disease-causing mutants has been performed to determine the function of those residues [Sloane04].

Studies with dimerization-deficient accC mutants showed that only dimeric biotin carboxylase fulfills its physiological function in vivo [Smith12].

Gene Citations: [Karow92a, Li93]

Locations: cytosol

Map Position: [3,403,939 -> 3,405,288] (73.37 centisomes)
Length: 1350 bp / 449 aa

Molecular Weight of Polypeptide: 49.321 kD (from nucleotide sequence)

pI: 7.08

Unification Links: ASAP:ABE-0010677 , CGSC:29834 , DIP:DIP-9035N , EchoBASE:EB0272 , EcoGene:EG10276 , EcoliWiki:b3256 , Mint:MINT-1266968 , ModBase:P24182 , OU-Microarray:b3256 , PortEco:accC , PR:PRO_000022034 , Pride:P24182 , Protein Model Portal:P24182 , RefSeq:NP_417722 , RegulonDB:EG10276 , SMR:P24182 , String:511145.b3256 , UniProt:P24182

Relationship Links: InterPro:IN-FAMILY:IPR004549 , InterPro:IN-FAMILY:IPR005479 , InterPro:IN-FAMILY:IPR005481 , InterPro:IN-FAMILY:IPR005482 , InterPro:IN-FAMILY:IPR011054 , InterPro:IN-FAMILY:IPR011761 , InterPro:IN-FAMILY:IPR011764 , InterPro:IN-FAMILY:IPR013815 , InterPro:IN-FAMILY:IPR013816 , InterPro:IN-FAMILY:IPR016185 , PDB:Structure:1BNC , PDB:Structure:1DV1 , PDB:Structure:1DV2 , PDB:Structure:1K69 , PDB:Structure:2GPS , PDB:Structure:2GPW , PDB:Structure:2J9G , PDB:Structure:2V58 , PDB:Structure:2V59 , PDB:Structure:2V5A , PDB:Structure:2VR1 , PDB:Structure:2W6M , PDB:Structure:2W6N , PDB:Structure:2W6O , PDB:Structure:2W6P , PDB:Structure:2W6Q , PDB:Structure:2W6Z , PDB:Structure:2W70 , PDB:Structure:2W71 , PDB:Structure:3G8C , PDB:Structure:3G8D , PDB:Structure:3JZF , PDB:Structure:3JZI , PDB:Structure:3RUP , PDB:Structure:3RV3 , PDB:Structure:3RV4 , PDB:Structure:4HR7 , Pfam:IN-FAMILY:PF00289 , Pfam:IN-FAMILY:PF02785 , Pfam:IN-FAMILY:PF02786 , Prosite:IN-FAMILY:PS00866 , Prosite:IN-FAMILY:PS00867 , Prosite:IN-FAMILY:PS50975 , Prosite:IN-FAMILY:PS50979 , Smart:IN-FAMILY:SM00878

In Paralogous Gene Group: 10 (2 members)

Gene-Reaction Schematic: ?

Genetic Regulation Schematic: ?

GO Terms:

Biological Process: GO:0006633 - fatty acid biosynthetic process Inferred from experiment Inferred by computational analysis [UniProtGOA11a, Davis00]
GO:0045717 - negative regulation of fatty acid biosynthetic process Inferred from experiment [AbdelHamid07]
GO:0006629 - lipid metabolic process Inferred by computational analysis [UniProtGOA11a]
GO:0006631 - fatty acid metabolic process Inferred by computational analysis [UniProtGOA11a]
GO:0008152 - metabolic process Inferred by computational analysis [GOA01a]
GO:2001295 - malonyl-CoA biosynthetic process Inferred by computational analysis [UniProtGOA12]
Molecular Function: GO:0004075 - biotin carboxylase activity Inferred from experiment Inferred by computational analysis [GOA01, GOA01a, Davis00]
GO:0005515 - protein binding Inferred from experiment [Rajagopala14, Arifuzzaman06, Butland05]
GO:0042803 - protein homodimerization activity Inferred from experiment [Smith12]
GO:0000166 - nucleotide binding Inferred by computational analysis [UniProtGOA11a]
GO:0003824 - catalytic activity Inferred by computational analysis [GOA01a]
GO:0003989 - acetyl-CoA carboxylase activity Inferred by computational analysis [GOA01]
GO:0005524 - ATP binding Inferred by computational analysis [UniProtGOA11a, GOA01a]
GO:0016874 - ligase activity Inferred by computational analysis [UniProtGOA11a, GOA01a]
GO:0046872 - metal ion binding Inferred by computational analysis [GOA01a]
Cellular Component: GO:0005829 - cytosol Inferred from experiment Inferred by computational analysis [DiazMejia09, Ishihama08, LopezCampistrou05]
GO:0005737 - cytoplasm Inferred by curator [Davis00]

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

Essentiality data for accC knockouts: ?

Growth Medium Growth? T (°C) O2 pH Osm/L Growth Observations
LB Lennox No 37 Aerobic 7   No [Baba06, Comment 1]

Enzymatic reaction of: biotin carboxylase

Synonyms: biotin carboxyl carrier protein:carbon dioxide ligase (ADP-forming)

EC Number: 6.3.4.14

a biotinylated [BCCP dimer] + hydrogen carbonate + ATP <=> a carboxylated-biotinylated [BCCP dimer] + ADP + phosphate + H+

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. [Polakis74]

Alternative Substrates for a biotinylated [BCCP dimer]: biotin [Kondo84a ]

In Pathways: biotin-carboxyl carrier protein assembly

Summary:
The acetyl-CoA carboxylase complex is composed of four different subunits. One of which, biotin carboxylase, mediates the first step of the acetyl-CoA carboxylase reaction. The overall reaction takes place in two distinct half-reactions, with a carboxyltransferase carrying out the second half [Kondo91, Magnuson93].

Inhibitors (Competitive): phosphonoacetate [Blanchard99a, Comment 2]

Inhibitors (Noncompetitive): biotin [Blanchard99a, Comment 3] , phosphonoacetate [Blanchard99a, Comment 4]

Primary Physiological Regulators of Enzyme Activity: biotin


Subunit of: acetyl-CoA carboxylase

Subunit composition of acetyl-CoA carboxylase = [(AccA)2(AccD)2][(AccC)2][(AccB)2]
         acetyl-CoA carboxyltransferase = (AccA)2(AccD)2 (extended summary available)
                 acetyl-CoA carboxyltransferase, α subunit = AccA (summary available)
                 acetyl-CoA carboxyltransferase, β subunit = AccD (summary available)
         biotin carboxylase = (AccC)2
         biotin carboxyl carrier protein (dimer) = (AccB)2 (summary available)
                 biotinylated biotin-carboxyl carrier protein = AccB

Summary:
The enzyme acetyl-CoA carboxylase is one of the key enzymes in the biosynthesis of fatty acids (see superpathway of fatty acid biosynthesis initiation (E. coli)). The enzyme belongs to the family of enzymes that catalyze the intermolecular transfer of carboxyl groups via the transient formation of a carboxyphosphate intermediate covalently linked to a biotin prosthetic group [Barber05]. For a thorough discussion of this protein, please see the pathway biotin-carboxyl carrier protein assembly.

The E. coli enzyme complex is composed of two catalytic units and one carrier protein, encoded by four different genes. The catalytic units are biotin carboxylase (BC), a homodimer encoded by the accC gene, and acetyl-CoA carboxylase (ACCT), an α2β2 tetramer, encoded by the accA and accD genes. The carrier protein is the biotin carboxyl carrier protein (dimer) (BCCP), a homodimer encoded by the accB gene.

The BCCP monomer is biotinylated by the enzyme biotin-[acetyl-CoA-carboxylase] ligase. Following dimerization of the biotinylated monomers, biotin carboxylase (BC) catalyzes the addition of CO2 to the carrier protein dimer, forming a carboxylated-biotinylated [BCCP dimer] (carboxy-BCCP). a carboxylated-biotinylated [BCCP dimer] in turn is the substrate for ACCT, which transfers the carboxy group to acetyl-CoA, resulting in the formation of malonyl-CoA and the regeneration of biotin carboxyl carrier protein (dimer). Both biotinylation and carboxylation of the carrier protein require ATP, while the last step, transfer of the carboxy group to acetyl-CoA, does not [Barber05].

Coordinated overexpression of accA, accB, accC and accD increases the biosynthesis of fatty acids [Davis00].

Review: [Cronan02]

GO Terms:

Molecular Function: GO:0003989 - acetyl-CoA carboxylase activity Inferred from experiment [Soriano06]


Enzymatic reaction of: acetyl-CoA carboxylase

EC Number: 6.4.1.2

ATP + acetyl-CoA + hydrogen carbonate <=> malonyl-CoA + ADP + phosphate + H+

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.

In Pathways: superpathway of fatty acid biosynthesis I (E. coli) , superpathway of fatty acid biosynthesis initiation (E. coli) , fatty acid biosynthesis initiation I

Summary:
Acetyl-CoA carboxylase is inhibited by acylated derivatives of ACP. The inhibition is of a mixed type, i.e. a combination of competitive and noncompetitive inhibition. The competitive nature of the inhibition suggests an interaction with the acetyl-CoA binding site. This in turn suggests that the acyl-ACP is binding with the acetyl-CoA carboxyltransferase component of the enzyme complex. [Davis01]

Cofactors or Prosthetic Groups: biotin

Inhibitors (Other): an apo-[acp] [Davis01]

Kinetic Parameters:

Substrate
Km (μM)
Citations
acetyl-CoA
18.0
[Soriano06]
ATP
60.0
[Soriano06]


Sequence Features

Feature Class Location Citations Comment
Conserved-Region 1 -> 445
[UniProt09]
UniProt: Biotin carboxylation;
Mutagenesis-Variant 19
[Shen06a, UniProt11]
Alternate sequence: R → E; UniProt: Loss of homodimerization. No effect on ATP binding.
Mutagenesis-Variant 23
[Shen06a, UniProt11]
Alternate sequence: E → R; UniProt: Loss of homodimerization. No effect on ATP binding.
Amino-Acid-Sites-That-Bind 116
[UniProt10]
UniProt: ATP;
Conserved-Region 120 -> 317
[UniProt09]
UniProt: ATP-grasp;
Sequence-Conflict 136
[Alix89, UniProt10]
Alternate sequence: G → A; UniProt: (in Ref. 7);
Sequence-Conflict 160
[Alix89, UniProt10]
Alternate sequence: A → P; UniProt: (in Ref. 7);
Amino-Acid-Sites-That-Bind 201
[UniProt10]
UniProt: ATP;
Amino-Acid-Sites-That-Bind 236
[UniProt10]
UniProt: ATP;
Sequence-Conflict 260 -> 261
[Li92d, UniProt10]
Alternate sequence: CA → SR; UniProt: (in Ref. 2);
Active-Site 292
[UniProt10a]
UniProt: Non-Experimental Qualifier: potential;
Sequence-Conflict 313
[Kondo91, UniProt10]
Alternate sequence: L → M; UniProt: (in Ref. 1; AAA23748);
Mutagenesis-Variant 363
[Shen06a, UniProt11]
Alternate sequence: F → A; UniProt: Loss of homodimerization. No effect on ATP binding.
Mutagenesis-Variant 366
[Shen06a, UniProt11]
Alternate sequence: R → E; UniProt: Loss of homodimerization. No effect on ATP binding.


Gene Local Context (not to scale): ?

Transcription Unit:

Notes:

History:
10/20/97 Gene b3256 from Blattner lab Genbank (v. M52) entry merged into EcoCyc gene EG10276; confirmed by SwissProt match.


References

AbdelHamid07: Abdel-Hamid AM, Cronan JE (2007). "Coordinate expression of the acetyl coenzyme A carboxylase genes, accB and accC, is necessary for normal regulation of biotin synthesis in Escherichia coli." J Bacteriol 189(2);369-76. PMID: 17056747

Alix89: Alix JH (1989). "A rapid procedure for cloning genes from lambda libraries by complementation of E. coli defective mutants: application to the fabE region of the E. coli chromosome." DNA 8(10);779-89. PMID: 2575489

Arifuzzaman06: Arifuzzaman M, Maeda M, Itoh A, Nishikata K, Takita C, Saito R, Ara T, Nakahigashi K, Huang HC, Hirai A, Tsuzuki K, Nakamura S, Altaf-Ul-Amin M, Oshima T, Baba T, Yamamoto N, Kawamura T, Ioka-Nakamichi T, Kitagawa M, Tomita M, Kanaya S, Wada C, Mori H (2006). "Large-scale identification of protein-protein interaction of Escherichia coli K-12." Genome Res 16(5);686-91. PMID: 16606699

Baba06: Baba T, Ara T, Hasegawa M, Takai Y, Okumura Y, Baba M, Datsenko KA, Tomita M, Wanner BL, Mori H (2006). "Construction of Escherichia coli K-12 in-frame, single-gene knockout mutants: the Keio collection." Mol Syst Biol 2;2006.0008. PMID: 16738554

Barber05: Barber MC, Price NT, Travers MT (2005). "Structure and regulation of acetyl-CoA carboxylase genes of metazoa." Biochim Biophys Acta 1733(1);1-28. PMID: 15749055

Blanchard99a: Blanchard CZ, Amspacher D, Strongin R, Waldrop GL (1999). "Inhibition of biotin carboxylase by a reaction intermediate analog: implications for the kinetic mechanism." Biochem Biophys Res Commun 1999;266(2);466-71. PMID: 10600526

Butland05: Butland G, Peregrin-Alvarez JM, Li J, Yang W, Yang X, Canadien V, Starostine A, Richards D, Beattie B, Krogan N, Davey M, Parkinson J, Greenblatt J, Emili A (2005). "Interaction network containing conserved and essential protein complexes in Escherichia coli." Nature 433(7025);531-7. PMID: 15690043

Cronan02: Cronan JE, Waldrop GL (2002). "Multi-subunit acetyl-CoA carboxylases." Prog Lipid Res 41(5);407-35. PMID: 12121720

Davis00: Davis MS, Solbiati J, Cronan JE (2000). "Overproduction of acetyl-CoA carboxylase activity increases the rate of fatty acid biosynthesis in Escherichia coli." J Biol Chem 275(37);28593-8. PMID: 10893421

Davis01: Davis MS, Cronan, Jr. JE (2001). "Inhibition of Escherichia coli acetyl coenzyme A carboxylase by acyl-acyl carrier protein." J Bacteriol. 183(4):1499-503. PMID: 11157970

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

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."

Ishihama08: Ishihama Y, Schmidt T, Rappsilber J, Mann M, Hartl FU, Kerner MJ, Frishman D (2008). "Protein abundance profiling of the Escherichia coli cytosol." BMC Genomics 9;102. PMID: 18304323

Karow92a: Karow M, Fayet O, Georgopoulos C (1992). "The lethal phenotype caused by null mutations in the Escherichia coli htrB gene is suppressed by mutations in the accBC operon, encoding two subunits of acetyl coenzyme A carboxylase." J Bacteriol 174(22);7407-18. PMID: 1358874

Kondo84a: Kondo H, Uno S, Komizo Y, Sunamoto J (1984). "Importance of methionine residues in the enzymatic carboxylation of biotin-containing peptides representing the local biotinyl site of E. coli acetyl-CoA carboxylase." Int J Pept Protein Res 1984;23(6);559-64. PMID: 6147321

Kondo91: Kondo H, Shiratsuchi K, Yoshimoto T, Masuda T, Kitazono A, Tsuru D, Anai M, Sekiguchi M, Tanabe T (1991). "Acetyl-CoA carboxylase from Escherichia coli: gene organization and nucleotide sequence of the biotin carboxylase subunit." Proc Natl Acad Sci U S A 1991;88(21);9730-3. PMID: 1682920

Li92d: Li SJ, Cronan JE (1992). "The gene encoding the biotin carboxylase subunit of Escherichia coli acetyl-CoA carboxylase." J Biol Chem 267(2);855-63. PMID: 1370469

Li93: Li SJ, Cronan JE (1993). "Growth rate regulation of Escherichia coli acetyl coenzyme A carboxylase, which catalyzes the first committed step of lipid biosynthesis." J Bacteriol 1993;175(2);332-40. PMID: 7678242

LopezCampistrou05: Lopez-Campistrous A, Semchuk P, Burke L, Palmer-Stone T, Brokx SJ, Broderick G, Bottorff D, Bolch S, Weiner JH, Ellison MJ (2005). "Localization, annotation, and comparison of the Escherichia coli K-12 proteome under two states of growth." Mol Cell Proteomics 4(8);1205-9. PMID: 15911532

Magnuson93: Magnuson K, Jackowski S, Rock CO, Cronan JE (1993). "Regulation of fatty acid biosynthesis in Escherichia coli." Microbiol Rev 1993;57(3);522-42. PMID: 8246839

Polakis74: Polakis SE, Guchhait RB, Zwergel EE, Lane MD, Cooper TG (1974). "Acetyl coenzyme A carboxylase system of Escherichia coli. Studies on the mechanisms of the biotin carboxylase- and carboxyltransferase-catalyzed reactions." J Biol Chem 249(20);6657-67. PMID: 4154091

Rajagopala14: Rajagopala SV, Sikorski P, Kumar A, Mosca R, Vlasblom J, Arnold R, Franca-Koh J, Pakala SB, Phanse S, Ceol A, Hauser R, Siszler G, Wuchty S, Emili A, Babu M, Aloy P, Pieper R, Uetz P (2014). "The binary protein-protein interaction landscape of Escherichia coli." Nat Biotechnol 32(3);285-90. PMID: 24561554

Shen06a: Shen Y, Chou CY, Chang GG, Tong L (2006). "Is dimerization required for the catalytic activity of bacterial biotin carboxylase?." Mol Cell 22(6);807-18. PMID: 16793549

Sloane04: Sloane V, Waldrop GL (2004). "Kinetic characterization of mutations found in propionic acidemia and methylcrotonylglycinuria: evidence for cooperativity in biotin carboxylase." J Biol Chem 279(16);15772-8. PMID: 14960587

Smith12: Smith AC, Cronan JE (2012). "Dimerization of the bacterial biotin carboxylase subunit is required for acetyl coenzyme A carboxylase activity in vivo." J Bacteriol 194(1);72-8. PMID: 22037404

Soriano06: Soriano A, Radice AD, Herbitter AH, Langsdorf EF, Stafford JM, Chan S, Wang S, Liu YH, Black TA (2006). "Escherichia coli acetyl-coenzyme A carboxylase: characterization and development of a high-throughput assay." Anal Biochem 349(2);268-76. PMID: 16325142

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

UniProt10: UniProt Consortium (2010). "UniProt version 2010-11 released on 2010-11-02 00:00:00." Database.

UniProt10a: 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."

UniProtGOA12: UniProt-GOA (2012). "Gene Ontology annotation based on UniPathway vocabulary mapping."

Other References Related to Gene Regulation

James04: James ES, Cronan JE (2004). "Expression of two Escherichia coli acetyl-CoA carboxylase subunits is autoregulated." J Biol Chem 279(4);2520-7. PMID: 14594796

Vanet93: Vanet A, Plumbridge JA, Alix JH (1993). "Cotranscription of two genes necessary for ribosomal protein L11 methylation (prmA) and pantothenate transport (panF) in Escherichia coli K-12." J Bacteriol 1993;175(22);7178-88. PMID: 8226664


Report Errors or Provide Feedback
Please cite the following article in publications resulting from the use of EcoCyc: Nucleic Acids Research 41:D605-12 2013
Page generated by SRI International Pathway Tools version 18.5 on Thu Dec 18, 2014, BIOCYC13A.