MetaCyc Enzyme: phosphopantetheine adenylyltransferase

Gene: coaD Accession Numbers: EG11190 (MetaCyc), b3634, ECK3624

Synonyms: yicA, kdtB, PPAT

Species: Escherichia coli K-12 substr. MG1655

Subunit composition of phosphopantetheine adenylyltransferase = [CoaD]6
         pantetheine-phosphate adenylyltransferase monomer = CoaD

Phosphopantetheine adenylyltransferase (PPAT) catalyzes the transfer of an adenyly group from ATP to 4'-phosphopantetheine [Geerlof99]. This is the penultimate reaction and a secondary rate-limiting step in CoA biosynthesis [Jackowski84].

Coenzyme A binds to the enzyme, but did not appear to influence catalytic activity of the reverse reaction [Geerlof99]. However, CoA is a competitive inhibitor of the forward reaction [Miller07].

The enzyme is homohexameric in solution, behaving as a dimer of trimers [Geerlof99]. Crystal structures of PPAT have been solved, and the catalytic mechanism and substrate interactions have been characterized [Izard99, Izard99a, Izard02, Izard03]. The reverse reaction appears to proceed via a ternary complex mechanism [Geerlof99]; product inhibition studies of the forward reaction are consistent with a random bi-bi kinetic mechanism [Miller07].

coaD is essential for growth in complex media [Freiberg01, Gerdes02]. CoaD is not similar to the mammalian PPAT and is therefore a potential antimicrobial drug target; inhibitors of the enzyme have been found and tested [Zhao03].

Citations: [Miller10]

Locations: cytosol

Map Position: [3,807,848 -> 3,808,327]

Molecular Weight of Polypeptide: 17.837 kD (from nucleotide sequence), 18.4 kD (experimental) [Geerlof99]

Molecular Weight of Multimer: 108.0 kD (experimental) [Geerlof99]

Unification Links: ASAP:ABE-0011875, CGSC:33900, DIP:DIP-35966N, EchoBASE:EB1176, EcoGene:EG11190, EcoliWiki:b3634, EcoO157Cyc:KDTB-MONOMER, ModBase:P0A6I6, OU-Microarray:b3634, PortEco:coaD, PR:PRO_000022310, Protein Model Portal:P0A6I6, RefSeq:NP_418091, RegulonDB:EG11190, SMR:P0A6I6, String:511145.b3634, UniProt:P0A6I6

Relationship Links: InterPro:IN-FAMILY:IPR001980, InterPro:IN-FAMILY:IPR004821, InterPro:IN-FAMILY:IPR014729, PDB:Structure:1B6T, PDB:Structure:1GN8, PDB:Structure:1H1T, PDB:Structure:1QJC, Pfam:IN-FAMILY:PF01467, Prints:IN-FAMILY:PR01020

Gene-Reaction Schematic

Gene-Reaction Schematic

GO Terms:
Biological Process:
Inferred from experimentInferred by computational analysisGO:0015937 - coenzyme A biosynthetic process [UniProtGOA12, UniProtGOA11a, GOA06, GOA01a, Miller07]
Inferred by computational analysisGO:0009058 - biosynthetic process [GOA01a]
Molecular Function:
Inferred from experimentInferred by computational analysisGO:0004595 - pantetheine-phosphate adenylyltransferase activity [GOA06, GOA01, GOA01a, Miller07]
Inferred by computational analysisGO:0000166 - nucleotide binding [UniProtGOA11a]
Inferred by computational analysisGO:0003824 - catalytic activity [GOA01a]
Inferred by computational analysisGO:0005524 - ATP binding [UniProtGOA11a]
Inferred by computational analysisGO:0016740 - transferase activity [UniProtGOA11a]
Inferred by computational analysisGO:0016779 - nucleotidyltransferase activity [UniProtGOA11a]
Cellular Component:
Inferred by computational analysisGO:0005737 - cytoplasm [UniProtGOA11, UniProtGOA11a, GOA06]
Inferred by computational analysisGO:0005829 - cytosol [DiazMejia09]

MultiFun Terms: metabolismbiosynthesis of building blockscofactors, small molecule carriersCoenzyme A and its modification

Imported from EcoCyc 30-Sep-2015 by Paley S, SRI International

Enzymatic reaction of: phosphopantetheine adenylyltransferase

Inferred from experiment

Synonyms: dephospho-CoA pyrophosphorylase, ATP:pantetheine-4'-phosphate adenylyltransferase, pantetheine-phosphate adenylyltransferase

EC Number:

4'-phosphopantetheine + ATP + H+ → 3'-dephospho-CoA + diphosphate

The direction shown, i.e. which substrates are on the left and right sides, is in accordance with the Enzyme Commission system.

The reaction is favored in the direction shown.

In Pathways: pantothenate and coenzyme A biosynthesis I, coenzyme A biosynthesis I

Imported from EcoCyc 30-Sep-2015 by Paley S, SRI International

Although enzyme assays have been performed in both the forward and reverse direction [Geerlof99, Miller07], the removal of PPi by pyrophospatase in vivo will strongly favor the forward direction. The equilibrium constant in vitro is between 1.25 and 1.95, favoring the forward direction [Miller07].

Cofactors or Prosthetic Groups: Mg2+ [Geerlof99]

Inhibitors (Competitive): coenzyme A [Miller07]

Primary Physiological Regulators of Enzyme Activity: coenzyme A

Kinetic Parameters:
Substrate Km (μM) kcat (sec-1) kcat/Km (sec-1 μM-1) Citations
3'-dephospho-CoA 17.0 [Miller07, BRENDA14]
3'-dephospho-CoA 7.0 [Izard02, BRENDA14]
3'-dephospho-CoA 7.0 9.2e-4 1.3e-4 [Geerlof99, BRENDA14]
4'-phosphopantetheine 4.7 [Miller07]
ATP 220.0 [Miller07, BRENDA14]
diphosphate 22.0 [Geerlof99, BRENDA14]
diphosphate 230.0, 220.0 [Miller07, BRENDA14]

pH(opt): 6.9 [Geerlof99]

10/20/97 Gene b3634 from Blattner lab Genbank (v. M52) entry merged into EcoCyc gene EG11190.


BRENDA14: BRENDA team (2014). Imported from BRENDA version existing on Aug 2014.

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

Freiberg01: Freiberg C, Wieland B, Spaltmann F, Ehlert K, Brotz H, Labischinski H (2001). "Identification of novel essential Escherichia coli genes conserved among pathogenic bacteria." J Mol Microbiol Biotechnol 3(3);483-9. PMID: 11361082

Geerlof99: Geerlof A, Lewendon A, Shaw WV (1999). "Purification and characterization of phosphopantetheine adenylyltransferase from Escherichia coli." J Biol Chem 1999;274(38);27105-11. PMID: 10480925

Gerdes02: Gerdes SY, Scholle MD, D'Souza M, Bernal A, Baev MV, Farrell M, Kurnasov OV, Daugherty MD, Mseeh F, Polanuyer BM, Campbell JW, Anantha S, Shatalin KY, Chowdhury SA, Fonstein MY, Osterman AL (2002). "From genetic footprinting to antimicrobial drug targets: examples in cofactor biosynthetic pathways." J Bacteriol 184(16);4555-72. PMID: 12142426

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."

GOA06: GOA, SIB (2006). "Electronic Gene Ontology annotations created by transferring manual GO annotations between orthologous microbial proteins."

Izard02: Izard T (2002). "The crystal structures of phosphopantetheine adenylyltransferase with bound substrates reveal the enzyme's catalytic mechanism." J Mol Biol 315(4);487-95. PMID: 11812124

Izard03: Izard T (2003). "A novel adenylate binding site confers phosphopantetheine adenylyltransferase interactions with coenzyme A." J Bacteriol 185(14);4074-80. PMID: 12837781

Izard99: Izard T, Geerlof A (1999). "The crystal structure of a novel bacterial adenylyltransferase reveals half of sites reactivity." EMBO J 1999;18(8);2021-30. PMID: 10205156

Izard99a: Izard T, Geerlof A, Lewendon A, Barker JJ (1999). "Cubic crystals of phosphopantetheine adenylyltransferase from Escherichia coli." Acta Crystallogr D Biol Crystallogr 1999;55 ( Pt 6);1226-8. PMID: 10329792

Jackowski84: Jackowski S, Rock CO (1984). "Metabolism of 4'-phosphopantetheine in Escherichia coli." J Bacteriol 158(1);115-20. PMID: 6370952

Miller07: Miller JR, Ohren J, Sarver RW, Mueller WT, de Dreu P, Case H, Thanabal V (2007). "Phosphopantetheine adenylyltransferase from Escherichia coli: investigation of the kinetic mechanism and role in regulation of coenzyme A biosynthesis." J Bacteriol 189(22);8196-205. PMID: 17873050

Miller10: Miller JR, Thanabal V, Melnick MM, Lall M, Donovan C, Sarver RW, Lee DY, Ohren J, Emerson D (2010). "The use of biochemical and biophysical tools for triage of high-throughput screening hits - A case study with Escherichia coli phosphopantetheine adenylyltransferase." Chem Biol Drug Des 75(5);444-54. PMID: 20486930

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."

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

Zhao03: Zhao L, Allanson NM, Thomson SP, Maclean JK, Barker JJ, Primrose WU, Tyler PD, Lewendon A (2003). "Inhibitors of phosphopantetheine adenylyltransferase." Eur J Med Chem 38(4);345-9. PMID: 12750020

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Please cite the following article in publications resulting from the use of MetaCyc: Caspi et al, Nucleic Acids Research 42:D459-D471 2014
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