Escherichia coli K-12 substr. MG1655 Enzyme: imidazoleglycerol-phosphate dehydratase / histidinol-phosphatase

Gene: hisB Accession Numbers: EG10445 (EcoCyc), b2022, ECK2017

Regulation Summary Diagram: ?

Regulation summary diagram for hisB

Subunit composition of imidazoleglycerol-phosphate dehydratase / histidinol-phosphatase = [HisB]2

The bifunctional imidazoleglycerol-phosphate dehydratase / histidinol-phosphatase (HisB) carries out the sixth and eighth step of histidine biosynthesis. HisB catalyzes two key reactions in histidine biosynthesis. The first is dehydration of D-erythro-imidazole-glycerol-phosphate to yield imidazole acetol-phosphate [Parker95]. The second is a phosphatase reaction that converts L-histidinol-phosphate into histidinol [Grisolia82].

Much initial work was done on the gene and enzyme from Salmonella typhimurium. The two enzymatic activities were found to reside in distinct domains of the enzyme. The amino-terminal end was shown to have histidinol phosphate phosphatase activity, while the carboxy-terminal domain catalyzed the dehydration of imidazole glycerol-3-phosphate [Loper61, Brady73, Houston74, Chumley81]. A model for the evolution of the bifunctional hisB gene has been proposed [Brilli04].

The amino-terminal domain of HisB (HisB-N) belongs to the superfamily of haloacid dehalogenase (HAD)-like hydrolases. Using a variety of possible substrates (not including histidinol phosphate), no phosphatase activity was detected; thus, the enzyme may be highly substrate-specific. [Kuznetsova06]

Crystal structures of HisB-N isolated from E. coli O157:H7 have been solved and the functional significance of its metal ion requirements elucidated. A catalytic mechanism differing from that of other HAD-like hydrolases has been proposed [Rangarajan06].

A high-throughput study of protein complexes in E. coli has identified HisB as a homomultimeric protein [Lasserre06]. The E. coli O157:H7 HisB-N is a dimer both in solution and the crystal structure. The full-length HisB protein associates into large oligomers; the authors suggest that the basic unit of HisB is a hexamer [Rangarajan06].

Gene Citations: [Grisolia83, Alifano92]

Locations: cytosol

Map Position: [2,091,492 -> 2,092,559] (45.08 centisomes, 162°)
Length: 1068 bp / 355 aa

Molecular Weight of Polypeptide: 40.278 kD (from nucleotide sequence), 40.5 kD (experimental) [Carlomagno88 ]

Unification Links: ASAP:ABE-0006720 , CGSC:635 , DIP:DIP-9901N , EchoBASE:EB0440 , EcoGene:EG10445 , EcoliWiki:b2022 , ModBase:P06987 , OU-Microarray:b2022 , PortEco:hisB , PR:PRO_000022892 , Pride:P06987 , Protein Model Portal:P06987 , RefSeq:NP_416526 , RegulonDB:EG10445 , SMR:P06987 , String:511145.b2022 , UniProt:P06987

Relationship Links: InterPro:IN-FAMILY:IPR000807 , InterPro:IN-FAMILY:IPR005954 , InterPro:IN-FAMILY:IPR006543 , InterPro:IN-FAMILY:IPR006549 , InterPro:IN-FAMILY:IPR013954 , InterPro:IN-FAMILY:IPR020565 , InterPro:IN-FAMILY:IPR020566 , InterPro:IN-FAMILY:IPR020568 , InterPro:IN-FAMILY:IPR023214 , Panther:IN-FAMILY:PTHR23133:SF2 , PDB:IN-FAMILY:2FPR , PDB:IN-FAMILY:2FPS , PDB:IN-FAMILY:2FPU , PDB:IN-FAMILY:2FPW , PDB:IN-FAMILY:2FPX , Pfam:IN-FAMILY:PF00475 , Pfam:IN-FAMILY:PF08645 , Prosite:IN-FAMILY:PS00954 , Prosite:IN-FAMILY:PS00955

In Paralogous Gene Group: 64 (3 members)

Gene-Reaction Schematic: ?

Gene-Reaction Schematic

Genetic Regulation Schematic: ?

Genetic regulation schematic for hisB

GO Terms:

Biological Process: GO:0000105 - histidine biosynthetic process Inferred from experiment Inferred by computational analysis [UniProtGOA12, UniProtGOA11a, GOA06, GOA01, Parker95]
GO:0016311 - dephosphorylation Inferred from experiment Inferred by computational analysis [GOA06, GOA01a, GOA01, Grisolia82]
GO:0008152 - metabolic process Inferred by computational analysis [UniProtGOA11a]
GO:0008652 - cellular amino acid biosynthetic process Inferred by computational analysis [UniProtGOA11a]
Molecular Function: GO:0004401 - histidinol-phosphatase activity Inferred from experiment Inferred by computational analysis [GOA06, GOA01a, GOA01, Grisolia82]
GO:0004424 - imidazoleglycerol-phosphate dehydratase activity Inferred from experiment Inferred by computational analysis [GOA06, GOA01a, GOA01, Parker95]
GO:0005515 - protein binding Inferred from experiment [Rajagopala14]
GO:0042802 - identical protein binding Inferred from experiment [Rajagopala14]
GO:0003824 - catalytic activity Inferred by computational analysis [UniProtGOA11a]
GO:0016787 - hydrolase activity Inferred by computational analysis [UniProtGOA11a]
GO:0016791 - phosphatase activity Inferred by computational analysis [GOA01]
GO:0016829 - lyase activity Inferred by computational analysis [UniProtGOA11a]
Cellular Component: GO:0005737 - cytoplasm Inferred by computational analysis [UniProtGOA11, UniProtGOA11a, GOA06, GOA01]
GO:0005829 - cytosol Inferred by computational analysis [DiazMejia09]

MultiFun Terms: metabolism biosynthesis of building blocks amino acids histidine

Essentiality data for hisB knockouts: ?

Growth Medium Growth? T (°C) O2 pH Osm/L Growth Observations
LB enriched Yes 37 Aerobic 6.95   Yes [Gerdes03, Comment 1]
LB Lennox Yes 37 Aerobic 7   Yes [Baba06, Comment 2]
M9 medium with 0.4% glucose No 37 Aerobic 7.2 0.27 No [Patrick07, Comment 3]
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 2]
No [Feist07, Comment 4]

Curated 03-Oct-2006 by Keseler I , SRI International
Curated 22-Aug-2007 by Shearer A , SRI International
Last-Curated ? 07-Oct-2013 by Kubo A , SRI International

Enzymatic reaction of: imidazoleglycerol-phosphate dehydratase

Synonyms: D-erythro imidazoleglycerol-phosphate dehydratase-histidinol phosphate phosphatase

EC Number:

D-erythro-imidazole-glycerol-phosphate <=> imidazole acetol-phosphate + H2O

The reaction direction shown, that is, A + B ↔ C + D versus C + D ↔ A + B, is in accordance with the direction of enzyme catalysis.

The reaction is irreversible in the direction shown.

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

The abbreviation IGP is used commonly for imidazoleglycerol-phosphate. This is not to be confused with the IGP of the tryptophan pathway in which IGP signifies indole glycerol-phosphate.

Cofactors or Prosthetic Groups: Mg2+

Alternative Cofactors for Mg2+: Mn2+

Inhibitors (Competitive): 3-amino-1,2,4-triazole [Brady73] , phosphate [Brady73]

Inhibitors (Unknown Mechanism): Zn2+ [Brady73]

Enzymatic reaction of: histidinol-phosphatase

Synonyms: histidinolphosphate phosphatase, L-Histidinol-phosphate phosphohydrolase, HPase, HAD21

EC Number:

L-histidinol-phosphate + H2O <=> histidinol + phosphate

The reaction direction shown, that is, A + B ↔ C + D versus C + D ↔ A + B, is in accordance with the direction in which it was curated.

The reaction is irreversible in the direction shown.

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

Cofactors or Prosthetic Groups: Mg2+

Inhibitors (Competitive): L-histidine [Brady73] , histidinol [Brady73]

Sequence Features

Protein sequence of HisB with features indicated

Feature Class Location Citations Comment
Protein-Segment 1 -> 166
UniProt: Histidinol-phosphatase; Sequence Annotation Type: region of interest;
Protein-Segment 167 -> 355
UniProt: Imidazoleglycerol-phosphate dehydratase; Sequence Annotation Type: region of interest;

Gene Local Context (not to scale): ?

Gene local context diagram

Transcription Units:

Transcription-unit diagram

Transcription-unit diagram

Transcription-unit diagram


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 b2022 from Blattner lab Genbank (v. M52) entry merged into EcoCyc gene EG10445; 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

Brady73: Brady DR, Houston LL (1973). "Some properties of the catalytic sites of imidazoleglycerol phosphate dehydratase-histidinol phosphate phosphatase, a bifunctional enzyme from Salmonella typhimurium." J Biol Chem 1973;248(7);2588-92. PMID: 4349042

Brilli04: Brilli M, Fani R (2004). "Molecular evolution of hisB genes." J Mol Evol 58(2);225-37. PMID: 15042344

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

Chumley81: Chumley FG, Roth JR (1981). "Genetic fusions that place the lactose genes under histidine operon control." J Mol Biol 145(4);697-712. PMID: 6267294

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

Gerdes03: Gerdes SY, Scholle MD, Campbell JW, Balazsi G, Ravasz E, Daugherty MD, Somera AL, Kyrpides NC, Anderson I, Gelfand MS, Bhattacharya A, Kapatral V, D'Souza M, Baev MV, Grechkin Y, Mseeh F, Fonstein MY, Overbeek R, Barabasi AL, Oltvai ZN, Osterman AL (2003). "Experimental determination and system level analysis of essential genes in Escherichia coli MG1655." J Bacteriol 185(19);5673-84. PMID: 13129938

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.

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

Grisolia82: Grisolia V, Carlomagno MS, Bruni CB (1982). "Cloning and expression of the distal portion of the histidine operon of Escherichia coli K-12." J Bacteriol 151(2);692-700. PMID: 6284708

Grisolia83: Grisolia V, Riccio A, Bruni CB (1983). "Structure and function of the internal promoter (hisBp) of the Escherichia coli K-12 histidine operon." J Bacteriol 155(3);1288-96. PMID: 6309747

Houston74: Houston LL, Graham ME (1974). "Divalent metal ion effects on a mutant histidinol phosphate phosphatase from Salmonella typhimurium." Arch Biochem Biophys 162(2);513-22. PMID: 4366369

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

Kuznetsova06: Kuznetsova E, Proudfoot M, Gonzalez CF, Brown G, Omelchenko MV, Borozan I, Carmel L, Wolf YI, Mori H, Savchenko AV, Arrowsmith CH, Koonin EV, Edwards AM, Yakunin AF (2006). "Genome-wide analysis of substrate specificities of the Escherichia coli haloacid dehalogenase-like phosphatase family." J Biol Chem 281(47):36149-61. PMID: 16990279

Lasserre06: Lasserre JP, Beyne E, Pyndiah S, Lapaillerie D, Claverol S, Bonneu M (2006). "A complexomic study of Escherichia coli using two-dimensional blue native/SDS polyacrylamide gel electrophoresis." Electrophoresis 27(16);3306-21. PMID: 16858726

Loper61: Loper JC (1961). "Enzyme complementation in mixed extracts of mutants from the Salmonella histidine B locus." Proc Natl Acad Sci U S A 47;1440-50. PMID: 13763426

Parker95: Parker, A.R., Moore, J.A., Schwab, J.M., Davisson, V.J. (1995). "Escherichia coli Imidazoleglycerol Phosphate Dehydratase: Spectroscopic Characterization of the Enzymic Product and the Steric Course of the Reaction." Journal of the American Chemical Society.

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

Rajagopala14: Rajagopala SV, Sikorski P, Kumar A, Mosca R, Vlasblom J, Arnold R, Franca-Koh J, Pakala SB, Phanse S, Ceol A, Hauser R, Siszler G, Wuchty S, Emili A, Babu M, Aloy P, Pieper R, Uetz P (2014). "The binary protein-protein interaction landscape of Escherichia coli." Nat Biotechnol 32(3);285-90. PMID: 24561554

Rangarajan06: Rangarajan ES, Proteau A, Wagner J, Hung MN, Matte A, Cygler M (2006). "Structural snapshots of Escherichia coli histidinol phosphate phosphatase along the reaction pathway." J Biol Chem 281(49):37930-41. PMID: 16966333

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

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 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."

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

Lee12a: 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

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

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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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