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Escherichia coli K-12 substr. MG1655 Enzyme: CDP-diglyceride synthetase



Gene: cdsA Accession Numbers: EG10139 (EcoCyc), b0175, ECK0174

Synonyms: cds

Regulation Summary Diagram: ?

Summary:
CDP-diglyceride synthetase catalyzes the synthesis of a CDP-diacylglycerol, the activated form of a 1,2-diacyl-sn-glycerol 3-phosphate (phosphatidic acid). CDP-diacylglycerol is positioned at a branchpoint in the lipid biosynthetic pathway where it reacts with sn-glycerol 3-phosphate to form an L-1-phosphatidylglycerol-phosphate, or with L-serine to form an L-1-phosphatidylserine. It is the source of the phosphatidyl group for all of the major phospholipids in E. coli [KANFER64, Chang67, Carter68, Raetz73, Tunaitis73, Hirschberg72, Langley78].

The properties of both the partially purified [Langley78] and purified [Sparrow85] enzyme have been studied. Mutants in cdsA contain significantly elevated levels of a 1,2-diacyl-sn-glycerol 3-phosphate (phosphatidic acid) in vivo [Ganong80, Ganong82, Ganong83].

Reviews: [Dowhan97], and Cronan, J.E. Jr., and C.O. Rock (2008) "Biosynthesis of Membrane Lipids" EcoSal 3.6.4 [ECOSAL]

Gene Citations: [Icho85]

Locations: inner membrane

Map Position: [195,677 -> 196,534] (4.22 centisomes)
Length: 858 bp / 285 aa

Molecular Weight of Polypeptide: 31.454 kD (from nucleotide sequence), 27.0 kD (experimental) [Sparrow85 ]

pI: 9.11

Unification Links: ASAP:ABE-0000600 , CGSC:930 , EchoBASE:EB0137 , EcoGene:EG10139 , EcoliWiki:b0175 , OU-Microarray:b0175 , PortEco:cdsA , PR:PRO_000022266 , Protein Model Portal:P0ABG1 , RefSeq:NP_414717 , RegulonDB:EG10139 , String:511145.b0175 , UniProt:P0ABG1

Relationship Links: InterPro:IN-FAMILY:IPR000374 , Pfam:IN-FAMILY:PF01148 , Prosite:IN-FAMILY:PS01315

Gene-Reaction Schematic: ?

GO Terms:

Biological Process: GO:0016024 - CDP-diacylglycerol biosynthetic process Inferred from experiment Inferred by computational analysis [UniProtGOA12, Ganong82, Langley78]
GO:0006629 - lipid metabolic process Inferred by computational analysis [UniProtGOA11]
GO:0008654 - phospholipid biosynthetic process Inferred by computational analysis [UniProtGOA11]
Molecular Function: GO:0004605 - phosphatidate cytidylyltransferase activity Inferred from experiment Inferred by computational analysis [GOA01a, Langley78]
GO:0016740 - transferase activity Inferred by computational analysis [UniProtGOA11]
GO:0016772 - transferase activity, transferring phosphorus-containing groups Inferred by computational analysis [GOA01]
GO:0016779 - nucleotidyltransferase activity Inferred by computational analysis [UniProtGOA11]
Cellular Component: GO:0005886 - plasma membrane Inferred from experiment Inferred by computational analysis [UniProtGOA11a, UniProtGOA11, DiazMejia09, Daley05, Langley78]
GO:0016020 - membrane Inferred by computational analysis [UniProtGOA11, GOA01]
GO:0016021 - integral component of membrane Inferred by computational analysis [UniProtGOA11]

MultiFun Terms: cell structure membrane
metabolism biosynthesis of building blocks fatty acids and phosphatidic acid
metabolism biosynthesis of macromolecules (cellular constituents) phospholipid

Essentiality data for cdsA knockouts: ?

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

Credits:
Last-Curated ? 06-Jun-2013 by Fulcher C , SRI International


Enzymatic reaction of: CTP:phosphatidate cytidyltransferase (CDP-diglyceride synthetase)

Synonyms: CTP:phosphatidic acid cytidylyltransferase, CDP-diglyceride pyrophosphorylase, CDP-diglyceride synthase, CDP diacylglycerol synthase, CDP-DAG synthase, CDP-DG synthase, phosphatide cytidylyltransferase

EC Number: 2.7.7.41

CTP + a 1,2-diacyl-sn-glycerol 3-phosphate + H+ <=> a CDP-diacylglycerol + diphosphate

The reaction direction shown, that is, A + B ↔ C + D versus C + D ↔ A + B, is in accordance with the Enzyme Commission system.

The reaction is favored in the direction shown.

In Pathways: phospholipid biosynthesis I , CDP-diacylglycerol biosynthesis II , CDP-diacylglycerol biosynthesis I


Enzymatic reaction of: CTP:2,3,4-saturated L-phosphatidate cytidylyltransferase (CDP-diglyceride synthetase)

EC Number: 2.7.7.41

CTP + a 2,3,4-saturated L-phosphatidate + H+ <=> a CDP-2,3,4-saturated-diacylglycerol + diphosphate

The reaction direction shown, that is, A + B ↔ C + D versus C + D ↔ A + B, is in accordance with the Enzyme Commission system.

The reaction is physiologically favored in the direction shown.

Alternative Substrates for CTP [Comment 2 ]: dCTP [Langley78 ]

Summary:
The enzyme has an absolute requirement for a divalent cation, and K+ also enhanced activity [Langley78]. The catalyzed reaction is reversible in vitro [Sparrow85]. The enzyme has been shown to utilize both CTP and dCTP nucleotides in vitro, producing both CDP-diacylglycerol and dCDP-diacylglycerol. These two products also occur in vivo although their physiological significance is not known. The enzyme did not utilize ATP, UTP, dATP, dTTP or dGTP [Langley78, Ganong82].

The enzyme strikingly preferred a 1,2-diacyl-sn-glycerol 3-phosphate (phosphatidic acid) substrates containing at least one double bond in their fatty acyl moieties. The routine assay substrate was phosphatidic acid made from egg phosphatidylcholine [Sparrow85].

Cofactors or Prosthetic Groups: Mg2+ [Comment 3, Langley78], K+ [Comment 4, Langley78]

Activators (Unknown Mechanism): a phospholipid [Langley78] , AMP [Langley78, Comment 5] , digitonin [Langley78, Comment 6] , Brij 97 [Langley78]

Inhibitors (Competitive): dCTP [Langley78, Comment 7] , CTP [Langley78, Comment 8]

Inhibitors (Unknown Mechanism): EDTA [Langley78]


Sequence Features

Feature Class Location Citations Comment
Transmembrane-Region 31 -> 51
[UniProt10]
UniProt: Helical;; Non-Experimental Qualifier: potential;
Transmembrane-Region 56 -> 76
[UniProt10]
UniProt: Helical;; Non-Experimental Qualifier: potential;
Transmembrane-Region 93 -> 113
[UniProt10]
UniProt: Helical;; Non-Experimental Qualifier: potential;
Transmembrane-Region 121 -> 141
[UniProt10]
UniProt: Helical;; Non-Experimental Qualifier: potential;
Transmembrane-Region 151 -> 171
[UniProt10]
UniProt: Helical;; Non-Experimental Qualifier: potential;
Transmembrane-Region 190 -> 210
[UniProt10]
UniProt: Helical;; Non-Experimental Qualifier: potential;
Transmembrane-Region 213 -> 233
[UniProt10]
UniProt: Helical;; Non-Experimental Qualifier: potential;
Transmembrane-Region 264 -> 284
[UniProt10]
UniProt: Helical;; Non-Experimental Qualifier: potential;


Gene Local Context (not to scale): ?

Transcription Unit:

Notes:

History:
Peter D. Karp on Wed Jan 18, 2006:
Gene left-end position adjusted based on analysis performed in the 2005 E. coli annotation update [Riley06 ].
10/20/97 Gene b0175 from Blattner lab Genbank (v. M52) entry merged into EcoCyc gene EG10139; confirmed by SwissProt match.


References

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

Carter68: Carter JR (1968). "Cytidine triphosphate: phosphatidic acid cytidyltransferase in Escherichia coli." J Lipid Res 9(6);748-54. PMID: 4879388

Chang67: Chang YY, Kennedy EP (1967). "Pathways for the synthesis of glycerophosphatides in Escherichia coli." J Biol Chem 242(3);516-9. PMID: 5336962

Daley05: Daley DO, Rapp M, Granseth E, Melen K, Drew D, von Heijne G (2005). "Global topology analysis of the Escherichia coli inner membrane proteome." Science 308(5726);1321-3. PMID: 15919996

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

Dowhan97: Dowhan W (1997). "CDP-diacylglycerol synthase of microorganisms." Biochim Biophys Acta 1348(1-2);157-65. PMID: 9370328

ECOSAL: "Escherichia coli and Salmonella: Cellular and Molecular Biology." Online edition.

Ganong80: Ganong BR, Leonard JM, Raetz CR (1980). "Phosphatidic acid accumulation in the membranes of Escherichia coli mutants defective in CDP-diglyceride synthetase." J Biol Chem 255(4);1623-9. PMID: 6243645

Ganong82: Ganong BR, Raetz CR (1982). "Massive accumulation of phosphatidic acid in conditionally lethal CDP-diglyceride synthetase mutants and cytidine auxotrophs of Escherichia coli." J Biol Chem 257(1);389-94. PMID: 6273438

Ganong83: Ganong BR, Raetz CR (1983). "pH-sensitive CDP-diglyceride synthetase mutants of Escherichia coli: phenotypic suppression by mutations at a second site." J Bacteriol 153(2);731-8. PMID: 6296051

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.

Hirschberg72: Hirschberg CB, Kennedy EP (1972). "Mechanism of the enzymatic synthesis of cardiolipin in Escherichia coli." Proc Natl Acad Sci U S A 69(3);648-51. PMID: 4551982

Icho85: Icho T, Sparrow CP, Raetz CR (1985). "Molecular cloning and sequencing of the gene for CDP-diglyceride synthetase of Escherichia coli." J Biol Chem 260(22);12078-83. PMID: 2995358

KANFER64: KANFER J, KENNEDY EP (1964). "METABOLISM AND FUNCTION OF BACTERIAL LIPIDS. II. BIOSYNTHESIS OF PHOSPHOLIPIDS IN ESCHERICHIA COLI." J Biol Chem 239;1720-6. PMID: 14213340

Langley78: Langley KE, Kennedy EP (1978). "Partial purification and properties of CTP:phosphatidic acid cytidylyltransferase from membranes of Escherichia coli." J Bacteriol 1978;136(1);85-95. PMID: 30751

Raetz73: Raetz CR, Kennedy EP (1973). "Function of cytidine diphosphate-diglyceride and deoxycytidine diphosphate-diglyceride in the biogenesis of membrane lipids in Escherichia coli." J Biol Chem 248(3);1098-105. PMID: 4567788

Riley06: Riley M, Abe T, Arnaud MB, Berlyn MK, Blattner FR, Chaudhuri RR, Glasner JD, Horiuchi T, Keseler IM, Kosuge T, Mori H, Perna NT, Plunkett G, Rudd KE, Serres MH, Thomas GH, Thomson NR, Wishart D, Wanner BL (2006). "Escherichia coli K-12: a cooperatively developed annotation snapshot--2005." Nucleic Acids Res 34(1);1-9. PMID: 16397293

Sparrow85: Sparrow CP, Raetz CR (1985). "Purification and properties of the membrane-bound CDP-diglyceride synthetase from Escherichia coli." J Biol Chem 1985;260(22);12084-91. PMID: 2995359

Tunaitis73: Tunaitis E, Cronan JE (1973). "Characterization of the cardiolipin synthetase activity of Escherichia coli envelopes." Arch Biochem Biophys 155(2);420-7. PMID: 4574544

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

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

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

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


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 Wed Nov 26, 2014, biocyc13.