|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, Vallari87a]. 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 [Zhang04a], explaining earlier results [Clifton70]. Further inhibitors/substrates of pantothenate kinase have been designed and tested [Virga06].
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 [Yun00a]. The N-terminal region forms much of the dimer interface [Yun00a]. 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].
|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]
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
|MultiFun Terms:||metabolism → biosynthesis of building blocks → cofactors, small molecule carriers → Coenzyme A and its modification|
Enzymatic reaction of: pantothenate kinase
Synonyms: ATP:pantothenate 4'-phosphotransferase
EC Number: 126.96.36.199(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]
ATP binding to pantothenate kinase is highly cooperative; the Hill coefficient is 1.46 [Song94].
Primary Physiological Regulators of Enzyme Activity: coenzyme AKinetic Parameters:
|Substrate||Km (μM)||kcat (sec-1)||Citations|
|ATP||115.0, 406.0||0.071, 1.14||[Chetnani09, BRENDA14]|
pH(opt): 6.3 [Vallari87a]
|Feature Class||Location||Attached Group||Citations||Comment|
|Nucleotide-Phosphate-Binding-Region||95 -> 102||ATP|
10/20/97 Gene b3974 from Blattner lab Genbank (v. M52) entry merged into EcoCyc gene EG10922; confirmed by SwissProt match.
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
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
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
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
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
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
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
Yun00a: 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
Zhang04a: 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
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