Escherichia coli K-12 substr. MG1655 Enzyme: ATP phosphoribosyltransferase

Gene: hisG Accession Numbers: EG10449 (EcoCyc), b2019, ECK2014

Regulation Summary Diagram: ?

Regulation summary diagram for hisG

Subunit composition of ATP phosphoribosyltransferase = [HisG]2

ATP phosphoribosyltransferase (HisG) catalyzes the first step in the pathway of histidine biosynthesis.

HisG synthesizes phosphoribosyl-ATP via a displacement of the first carbon of 5-phosphoribosyl 1-pyrophosphate by the first nitrogen on the purine ring of ATP [Tebar76, Kronenberg75, Kleeman75].

ATP phosphoribosyltransferase functions as a dimer [Tebar78]. Interaction with histidine induces formation of a catalytically inactive hexamer. In this hexameric state, the active site is unavailable. In constrast, AMP inhibits HisG function by binding in the 5-phosphoribosyl 1-pyrophosphate site and occluding the ATP binding site [DallLarsen76, Lohkamp04]. Crystal structures of HisG bound to AMP and bound to phosphoribosyl-ATP have been solved to 2.7 Å and 2.9 Å resolution, respectively [Lohkamp00, Lohkamp04]. The structure of HisG has also been studied via spin-label and EPR methods [Tebar77, Tebar77a].

Gene Citations: [Alifano92]

Locations: cytosol

Map Position: [2,088,216 -> 2,089,115] (45.01 centisomes, 162°)
Length: 900 bp / 299 aa

Molecular Weight of Polypeptide: 33.367 kD (from nucleotide sequence)

Molecular Weight of Multimer: 67.0 kD (experimental) [Tebar78]

Unification Links: ASAP:ABE-0006713 , CGSC:630 , EchoBASE:EB0444 , EcoGene:EG10449 , EcoliWiki:b2019 , ModBase:P60757 , OU-Microarray:b2019 , PortEco:hisG , PR:PRO_000022896 , Pride:P60757 , Protein Model Portal:P60757 , RefSeq:NP_416523 , RegulonDB:EG10449 , SMR:P60757 , String:511145.b2019 , UniProt:P60757

Relationship Links: InterPro:IN-FAMILY:IPR001348 , InterPro:IN-FAMILY:IPR011322 , InterPro:IN-FAMILY:IPR013115 , InterPro:IN-FAMILY:IPR013820 , InterPro:IN-FAMILY:IPR015867 , InterPro:IN-FAMILY:IPR018198 , InterPro:IN-FAMILY:IPR020621 , Panther:IN-FAMILY:PTHR21403 , PDB:Structure:1h3d , PDB:Structure:1H3D , PDB:Structure:1q1k , PDB:Structure:1Q1K , Pfam:IN-FAMILY:PF01634 , Pfam:IN-FAMILY:PF08029 , Prosite:IN-FAMILY:PS01316

Gene-Reaction Schematic: ?

Gene-Reaction Schematic

Genetic Regulation Schematic: ?

Genetic regulation schematic for hisG

GO Terms:

Biological Process: GO:0000105 - histidine biosynthetic process Inferred from experiment Inferred by computational analysis [UniProtGOA12, UniProtGOA11a, GOA06, GOA01a, Kronenberg75]
GO:0008652 - cellular amino acid biosynthetic process Inferred by computational analysis [UniProtGOA11a]
Molecular Function: GO:0003879 - ATP phosphoribosyltransferase activity Inferred from experiment Inferred by computational analysis [GOA06, GOA01, GOA01a, Kronenberg75]
GO:0000166 - nucleotide binding Inferred by computational analysis [UniProtGOA11a]
GO:0000287 - magnesium ion binding Inferred by computational analysis [GOA06, GOA01a]
GO:0005524 - ATP binding Inferred by computational analysis [UniProtGOA11a]
GO:0016740 - transferase activity Inferred by computational analysis [UniProtGOA11a]
GO:0016757 - transferase activity, transferring glycosyl groups Inferred by computational analysis [UniProtGOA11a]
GO:0046872 - metal ion binding Inferred by computational analysis [UniProtGOA11a]
Cellular Component: GO:0005829 - cytosol Inferred from experiment Inferred by computational analysis [DiazMejia09, Ishihama08, LopezCampistrou05]
GO:0005737 - cytoplasm Inferred by computational analysis [UniProtGOA11, UniProtGOA11a, GOA06, GOA01a]

MultiFun Terms: metabolism biosynthesis of building blocks amino acids histidine

Essentiality data for hisG knockouts: ?

Growth Medium Growth? T (°C) O2 pH Osm/L Growth Observations
LB Lennox Yes 37 Aerobic 7   Yes [Baba06, Comment 1]
M9 medium with 0.4% glucose No 37 Aerobic 7.2 0.27 No [Patrick07, Comment 2]
M9 medium with 1% glycerol No 37 Aerobic 7.2 0.35 No [Joyce06]
MOPS medium with 0.4% glucose Indeterminate 37 Aerobic 7.2 0.22 Yes [Baba06, Comment 1]
No [Feist07, Comment 3]

Created 17-Aug-2007 by Shearer A , SRI International
Curated 17-Aug-2007 by Shearer A , SRI International
Last-Curated ? 07-Oct-2013 by Kubo A , SRI International

Enzymatic reaction of: ATP phosphoribosyltransferase

EC Number:

1-(5-phospho-β-D-ribosyl)-ATP + diphosphate <=> ATP + 5-phospho-α-D-ribose 1-diphosphate + 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.

This reaction is reversible.

In Pathways: superpathway of histidine, purine, and pyrimidine biosynthesis , L-histidine biosynthesis

This reaction is reversible [Kleeman75, Tebar76].

Dinitrophenol and AMP are both competitive inhibitors with respect to ATP [Tebar76, DallLarsen75].

Inhibitors (Allosteric): L-histidine [Tebar76]

Inhibitors (Competitive): 2,4-dinitrophenol [DallLarsen75] , AMP [Tebar76]

Primary Physiological Regulators of Enzyme Activity: AMP , L-histidine

Sequence Features

Protein sequence of HisG with features indicated

Feature Class Location Citations Comment
Sequence-Conflict 6
[Verde81, UniProt10]
UniProt: (in Ref. 6; CAA23549);
Sequence-Conflict 49 -> 50
[Carlomagno88, UniProt10]
UniProt: (in Ref. 1; CAA31811);
Sequence-Conflict 263
[Carlomagno88, UniProt10]
UniProt: (in Ref. 1; CAA31811);

Gene Local Context (not to scale): ?

Gene local context diagram

Transcription Units:

Transcription-unit diagram

Transcription-unit diagram

Transcription-unit diagram


10/20/97 Gene b2019 from Blattner lab Genbank (v. M52) entry merged into EcoCyc gene EG10449; confirmed by SwissProt match.


Alifano92: Alifano P, Carlomagno MS, Bruni CB (1992). "Location of the hisGDCBHAFI operon on the physical map of Escherichia coli." J Bacteriol 1992;174(11);3830-1. PMID: 1592835

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

Carlomagno88: Carlomagno MS, Chiariotti L, Alifano P, Nappo AG, Bruni CB (1988). "Structure and function of the Salmonella typhimurium and Escherichia coli K-12 histidine operons." J Mol Biol 1988;203(3);585-606. PMID: 3062174

DallLarsen75: Dall-Larsen T, Fasold H, Klungsoyr L, Kryvi H, Meyer C, Ortanderl F (1975). "Affinity labelling to - SH groups in adenosine - triphosphate - phosphoribosyl transferase with the dinitrophenyl group from S-dinitrophenyl-6-mercaptopurine-riboside 5'-phosphate." Eur J Biochem 60(1);103-7. PMID: 1204631

DallLarsen76: Dall-Larsen T, Klungsoyr L (1976). "The binding of specific ligands to adenosine-triphosphate phosphoribosyltransferase." Eur J Biochem 69(1);195-201. PMID: 991855

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

Feist07: Feist AM, Henry CS, Reed JL, Krummenacker M, Joyce AR, Karp PD, Broadbelt LJ, Hatzimanikatis V, Palsson BO (2007). "A genome-scale metabolic reconstruction for Escherichia coli K-12 MG1655 that accounts for 1260 ORFs and thermodynamic information." Mol Syst Biol 3;121. PMID: 17593909

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."

Goldschmidt70: Goldschmidt EP, Cater MS, Matney TS, Butler MA, Greene A (1970). "Genetic analysis of the histidine operon in Escherichia coli K12." Genetics 66(2);219-29. PMID: 4934197

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

Joyce06: Joyce AR, Reed JL, White A, Edwards R, Osterman A, Baba T, Mori H, Lesely SA, Palsson BO, Agarwalla S (2006). "Experimental and computational assessment of conditionally essential genes in Escherichia coli." J Bacteriol 188(23);8259-71. PMID: 17012394

Kleeman75: Kleeman J, Parsons SM (1975). "A sensitive assay for the reverse reaction of the first histidine biosynthetic enzyme." Anal Biochem 68(1);236-41. PMID: 1190438

Kronenberg75: Kronenberg HM, Vogel T, Goldberger RF (1975). "A new and highly sensitive assay for the ATP phosphoribosyltransferase that catalyzes the first step of histidine biosynthesis." Anal Biochem 65(1-2);380-8. PMID: 165751

Lohkamp00: Lohkamp B, Coggins JR, Lapthorn AJ (2000). "Purification, crystallization and preliminary X-ray crystallographic analysis of ATP-phosphoribosyltransferase from Escherichia coli." Acta Crystallogr D Biol Crystallogr 56(Pt 11);1488-91. PMID: 11185885

Lohkamp04: Lohkamp B, McDermott G, Campbell SA, Coggins JR, Lapthorn AJ (2004). "The structure of Escherichia coli ATP-phosphoribosyltransferase: identification of substrate binding sites and mode of AMP inhibition." J Mol Biol 336(1);131-44. PMID: 14741209

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

Patrick07: Patrick WM, Quandt EM, Swartzlander DB, Matsumura I (2007). "Multicopy suppression underpins metabolic evolvability." Mol Biol Evol 24(12);2716-22. PMID: 17884825

Tebar76: Tebar AR, Ballesteros AO (1976). "Kinetic properties of ATP phosphoribosyltransferase of Escherichia coli." Mol Cell Biochem 11(3);131-6. PMID: 781521

Tebar77: Tebar AR, Ballesteros A, Soria J (1977). "Spin label studies of ATP phosphoribosyltransferase of E. coli." Experientia 33(8);1014-6. PMID: 196892

Tebar77a: Tebar AR, Ballesteros A, Soria J (1977). "Mn2+ electron spin resonance studies on ATP phosphoribosyltransferase from E. coli." Experientia 33(10);1292-4. PMID: 198234

Tebar78: Tebar AR, Leyva JC, Laynez J, Ballesteros A (1978). "The action of inhibitors (histidine and AMP) on the ATP phosphoribosyltransferase of E. coli." Rev Esp Fisiol 34(2);159-66. PMID: 358336

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

Verde81: Verde P, Frunzio R, di Nocera PP, Blasi F, Bruni CB (1981). "Identification, nucleotide sequence and expression of the regulatory region of the histidine operon of Escherichia coli K-12." Nucleic Acids Res 9(9);2075-86. PMID: 6170941

Other References Related to Gene Regulation

Di78: Di Nocera PP, Blasi F, Di Lauro R, Frunzio R, Bruni CB (1978). "Nucleotide sequence of the attenuator region of the histidine operon of Escherichia coli K-12." Proc Natl Acad Sci U S A 75(9);4276-80. PMID: 360215

Frunzio81: Frunzio R, Bruni CB, Blasi F (1981). "In vivo and in vitro detection of the leader RNA of the histidine operon of Escherichia coli K-12." Proc Natl Acad Sci U S A 78(5);2767-71. PMID: 6166940

Lee12: Lee JH, Lennon CW, Ross W, Gourse RL (2012). "Role of the coiled-coil tip of Escherichia coli DksA in promoter control." J Mol Biol 416(4);503-17. PMID: 22200485

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Please cite the following article in publications resulting from the use of EcoCyc: Nucleic Acids Research 41:D605-12 2013
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