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MetaCyc Enzyme: pantothenate kinase

Gene: coaA Accession Numbers: EG10922 (MetaCyc), b3974, ECK3966

Synonyms: panK, rts, ts-9

Species: Escherichia coli K-12 substr. MG1655

Subunit composition of pantothenate kinase = [CoaA]2
         pantothenate kinase monomer = CoaA

Pantothenate kinase catalyzes the first step in the biosynthesis of coenzyme A, an essential cofactor that is involved in many reactions. It is also the most highly regulated step in the pathway [Jackowski81, Jackowski84].

Pantothenate kinase is sensitive to feedback inhibition by the CoA pool [Song94, Vallari87]. Mutants that are refractory to feedback inhibition, but retain catalytic activity, have been isolated; these mutants have a higher intracellular CoA content and secrete 4'-phosphopantetheine [Rock03].

The compounds N5-Pan and N7-Pan are competitive inhibitors of pantothenate kinase [Ivey04] and can be utilized as substrates of the CoA biosynthesis pathway [Strauss02]. The phosphopantothenimide moiety is transferred to ACP, rendering it incapable of supporting fatty acid biosynthesis. Thus, N5-Pan and N7-Pan are pro-antibiotics [Zhang04], explaining earlier results [Clifton70]. Further inhibitors/substrates of pantothenate kinase have been designed and tested [Virga06].

Utilization of two different translation start sites of coaA results in proteins that differ by eight amino acids at the N terminus [Song92, Song94].

Crystal structures of pantothenate kinase in complex with AMPPNP (a nonhydrolyzable analog of ATP) or CoA have been solved, showing that the phosphate binding sites of CoA and ATP overlap, which explains their kinetic competition [Yun00]. The N-terminal region forms much of the dimer interface [Yun00]. The crystal structure of the ternary complex with ADP and patothenate shows induced fit binding of pantothenate; a mechanism of phosphoryl transfer was proposed [Ivey04].

coaA is an essential gene [Gerdes02]. Temperature-sensitive alleles have been isolated [Vallari87a, Flaks66].

Locations: cytosol

Map Position: [4,172,099 <- 4,173,049]

Molecular Weight of Polypeptide: 36.36 kD (from nucleotide sequence)

Molecular Weight of Multimer: 69.0 kD (experimental) [Song94]

pI: 6.74

Unification Links: ASAP:ABE-0013003, CGSC:17731, EchoBASE:EB0915, EcoGene:EG10922, EcoliWiki:b3974, ModBase:P0A6I3, OU-Microarray:b3974, PortEco:coaA, PR:PRO_000022308, Pride:P0A6I3, Protein Model Portal:P0A6I3, RefSeq:NP_418405, RegulonDB:EG10922, SMR:P0A6I3, String:511145.b3974, UniProt:P0A6I3

Relationship Links: InterPro:IN-FAMILY:IPR004566, InterPro:IN-FAMILY:IPR006083, InterPro:IN-FAMILY:IPR027417, Panther:IN-FAMILY:PTHR10285:SF7, PDB:Structure:1ESM, PDB:Structure:1ESN, PDB:Structure:1SQ5, Pfam:IN-FAMILY:PF00485

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, Vallari87a]
Inferred by computational analysisGO:0008152 - metabolic process [GOA01a]
Inferred by computational analysisGO:0016310 - phosphorylation [UniProtGOA11a]
Molecular Function:
Inferred from experimentInferred by computational analysisGO:0004594 - pantothenate kinase activity [GOA06, GOA01, GOA01a, Song94]
Inferred from experimentInferred by computational analysisGO:0005524 - ATP binding [UniProtGOA11a, GOA06, GOA01a, Song94]
Inferred by computational analysisGO:0000166 - nucleotide binding [UniProtGOA11a]
Inferred by computational analysisGO:0016301 - kinase activity [UniProtGOA11a, GOA01a]
Inferred by computational analysisGO:0016740 - transferase activity [UniProtGOA11a]
Cellular Component:
Inferred by computational analysisGO:0005737 - cytoplasm [UniProtGOA11, UniProtGOA11a, GOA06, GOA01a]
Inferred by computational analysisGO:0005829 - cytosol [Gaudet10, 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: pantothenate kinase

Inferred from experiment

Synonyms: ATP:pantothenate 4'-phosphotransferase

EC Number:

(R)-pantothenate + ATP → (R)-4'-phosphopantothenate + ADP + H+

The direction shown, i.e. which substrates are on the left and right sides, is in accordance with the direction of enzyme catalysis.

The reaction is physiologically favored in the direction shown.

Alternative Substrates for (R)-pantothenate: N5-Pan [Strauss02]
Alternative Substrates for ATP: GTP [Vallari87]

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

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

ATP binding to pantothenate kinase is highly cooperative; the Hill coefficient is 1.46 [Song94].

Cofactors or Prosthetic Groups: Mg2+ [Vallari87]

Inhibitors (Competitive): N5-Pan [Ivey04], N7-Pan [Ivey04], coenzyme A [Vallari87, Song94, Comment 1]

Primary Physiological Regulators of Enzyme Activity: coenzyme A

Kinetic Parameters:
Substrate Km (μM) kcat (sec-1) Citations
(R)-pantothenate 41.0 [Ivey04, BRENDA14]
(R)-pantothenate 9.0 [Vallari87, BRENDA14]
(R)-pantothenate 136.0 [Spry08, BRENDA14]
(R)-pantothenate 36.0, 136.0 [Song94]
ATP 136.0 [Spry08, BRENDA14]
ATP 136.0 [Song94, BRENDA14]
ATP 115.0, 406.0 0.071, 1.14 [Chetnani09, BRENDA14]

pH(opt): 6.3 [Vallari87]

Sequence Features

Feature Class Location Attached Group Citations Comment
Nucleotide-Phosphate-Binding-Region 95 -> 102 ATP
Inferred by computational analysis[UniProt15]
UniProt: ATP.

10/20/97 Gene b3974 from Blattner lab Genbank (v. M52) entry merged into EcoCyc gene EG10922; confirmed by SwissProt match.


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

Chetnani09: Chetnani B, Das S, Kumar P, Surolia A, Vijayan M (2009). "Mycobacterium tuberculosis pantothenate kinase: possible changes in location of ligands during enzyme action." Acta Crystallogr D Biol Crystallogr 65(Pt 4);312-25. PMID: 19307712

Clifton70: Clifton G, Bryant SR, Skinner CG (1970). "N'-(substituted) pantothenamides, antimetabolites of pantothenic acid." Arch Biochem Biophys 137(2);523-8. PMID: 4909169

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

Flaks66: Flaks JG, Leboy PS, Birge EA, Kurland CG (1966). "Mutations and genetics concerned with the ribosome." Cold Spring Harb Symp Quant Biol 31;623-31. PMID: 4866408

Gaudet10: Gaudet P, Livstone M, Thomas P (2010). "Annotation inferences using phylogenetic trees." PMID: 19578431

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."

Ivey04: Ivey RA, Zhang YM, Virga KG, Hevener K, Lee RE, Rock CO, Jackowski S, Park HW (2004). "The structure of the pantothenate kinase.ADP.pantothenate ternary complex reveals the relationship between the binding sites for substrate, allosteric regulator, and antimetabolites." J Biol Chem 279(34);35622-9. PMID: 15136582

Jackowski81: Jackowski S, Rock CO (1981). "Regulation of coenzyme A biosynthesis." J Bacteriol 148(3);926-32. PMID: 6796563

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

Rock03: Rock CO, Park HW, Jackowski S (2003). "Role of feedback regulation of pantothenate kinase (CoaA) in control of coenzyme A levels in Escherichia coli." J Bacteriol 185(11);3410-5. PMID: 12754240

Song92: Song WJ, Jackowski S (1992). "Cloning, sequencing, and expression of the pantothenate kinase (coaA) gene of Escherichia coli." J Bacteriol 1992;174(20);6411-7. PMID: 1328157

Song92a: Song WJ, Jackowski S (1992). "coaA and rts are allelic and located at kilobase 3532 on the Escherichia coli physical map." J Bacteriol 174(5);1705-6. PMID: 1311303

Song94: Song WJ, Jackowski S (1994). "Kinetics and regulation of pantothenate kinase from Escherichia coli." J Biol Chem 1994;269(43);27051-8. PMID: 7929447

Spry08: Spry C, Kirk K, Saliba KJ (2008). "Coenzyme A biosynthesis: an antimicrobial drug target." FEMS Microbiol Rev 32(1);56-106. PMID: 18173393

Strauss02: Strauss E, Begley TP (2002). "The antibiotic activity of N-pentylpantothenamide results from its conversion to ethyldethia-coenzyme a, a coenzyme a antimetabolite." J Biol Chem 277(50);48205-9. PMID: 12372838

UniProt15: UniProt Consortium (2015). "UniProt version 2015-08 released on 2015-07-22." 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."

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

Vallari87: Vallari DS, Jackowski S, Rock CO (1987). "Regulation of pantothenate kinase by coenzyme A and its thioesters." J Biol Chem 1987;262(6);2468-71. PMID: 3029083

Vallari87a: Vallari DS, Rock CO (1987). "Isolation and characterization of temperature-sensitive pantothenate kinase (coaA) mutants of Escherichia coli." J Bacteriol 169(12);5795-800. PMID: 2824448

Virga06: Virga KG, Zhang YM, Leonardi R, Ivey RA, Hevener K, Park HW, Jackowski S, Rock CO, Lee RE (2006). "Structure-activity relationships and enzyme inhibition of pantothenamide-type pantothenate kinase inhibitors." Bioorg Med Chem 14(4);1007-20. PMID: 16213731

Yun00: Yun M, Park CG, Kim JY, Rock CO, Jackowski S, Park HW (2000). "Structural basis for the feedback regulation of Escherichia coli pantothenate kinase by coenzyme A." J Biol Chem 275(36);28093-9. PMID: 10862768

Zhang04: Zhang YM, Frank MW, Virga KG, Lee RE, Rock CO, Jackowski S (2004). "Acyl carrier protein is a cellular target for the antibacterial action of the pantothenamide class of pantothenate antimetabolites." J Biol Chem 279(49);50969-75. PMID: 15459190

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
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