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MetaCyc Polypeptide: imidazole glycerol phosphate synthase, HisF subunit

Gene: hisF Accession Numbers: EG10448 (MetaCyc), b2025, ECK2020

Synonyms: hisF enzyme

Species: Escherichia coli K-12 substr. MG1655

Component of: imidazole glycerol phosphate synthase (extended summary available)

Summary:
HisF is the synthase subunit of imidazole glycerol phosphate synthase (HisFH). HisFH catalyzes the fifth step of histidine biosynthesis, as well as generates aminoimidazole carboxamide ribonucleotide, an intermediate in purine nucleotide biosynthesis.

The two components of the HisFH dimer work together to catalyze the addition of nitrogen from glutamine to the imidazole ring of phosphoribulosylformimino-AICAR-phosphate to generate aminoimidazole carboxamide ribonucleotide, D-erythro-imidazole-glycerol-phosphate, and glutamate [Klem93]. Although isolated HisH has no activity, isolated HisF catalyzes an ammonia-dependent reaction that uses ammonia as a nitrogen donor in the place of the physiological donor glutamine [Klem93]. The kinetics of HisFH have been modeled [Demin04].

HisFH is a 1:1 dimer of HisF and HisH [Klem93]. The critical residues involved in subunit interaction in general and in the specific case of cooperation of the two active sites have been examined [Klem01, Myers05].

The predicted structure of HisFH, which shows a conserved core region and variable domain has been described [ODonoghue].

Locations: cytosol

Map Position: [2,093,868 -> 2,094,644]

Molecular Weight of Polypeptide: 28.454 kD (from nucleotide sequence)

Unification Links: ASAP:ABE-0006727 , CGSC:631 , EchoBASE:EB0443 , EcoGene:EG10448 , EcoliWiki:b2025 , ModBase:P60664 , OU-Microarray:b2025 , PortEco:hisF , PR:PRO_000022895 , Pride:P60664 , Protein Model Portal:P60664 , RefSeq:NP_416529 , RegulonDB:EG10448 , SMR:P60664 , String:511145.b2025 , UniProt:P60664

Relationship Links: InterPro:IN-FAMILY:IPR004651 , InterPro:IN-FAMILY:IPR006062 , InterPro:IN-FAMILY:IPR011060 , InterPro:IN-FAMILY:IPR013785 , Pfam:IN-FAMILY:PF00977

Gene-Reaction Schematic: ?

GO Terms:

Biological Process: GO:0000105 - histidine biosynthetic process Inferred from experiment Inferred by computational analysis [UniProtGOA12, UniProtGOA11a, GOA06, GOA01a, Klem93]
GO:0008152 - metabolic process Inferred by computational analysis [GOA01a]
GO:0008652 - cellular amino acid biosynthetic process Inferred by computational analysis [UniProtGOA11a]
Molecular Function: GO:0000107 - imidazoleglycerol-phosphate synthase activity Inferred from experiment Inferred by computational analysis [GOA06, GOA01a, Klem93]
GO:0003824 - catalytic activity Inferred by computational analysis [GOA01a]
GO:0016829 - lyase activity Inferred by computational analysis [UniProtGOA11a]
Cellular Component: GO:0005829 - cytosol Inferred from experiment Inferred by computational analysis [DiazMejia09, LopezCampistrou05]
GO:0009382 - imidazoleglycerol-phosphate synthase complex Inferred from experiment [Klem93]
GO:0005737 - cytoplasm Inferred by computational analysis [UniProtGOA11, UniProtGOA11a, GOA06, GOA01a]

MultiFun Terms: metabolism biosynthesis of building blocks amino acids histidine

Credits:
Imported from EcoCyc 16-Sep-2014 by Paley S , SRI International


Subunit of: imidazole glycerol phosphate synthase

Species: Escherichia coli K-12 substr. MG1655

Subunit composition of imidazole glycerol phosphate synthase = [HisH][HisF]
         imidazole glycerol phosphate synthase, HisH subunit = HisH (extended summary available)
         imidazole glycerol phosphate synthase, HisF subunit = HisF (extended summary available)

Summary:
Imidazole glycerol phosphate synthase (HisFH) is a heterodimer that carries out the fifth step in histidine biosynthesis, as well as generating aminoimidazole carboxamide ribonucleotide, an intermediate in purine nucleotide biosynthesis.

The two components of the HisFH dimer work together to catalyze the addition of nitrogen from glutamine to the imidazole ring of phosphoribulosylformimino-AICAR-phosphate to generate aminoimidazole carboxamide ribonucleotide, D-erythro-imidazole-glycerol-phosphate, and glutamate [Klem93]. Although isolated HisH has no activity, isolated HisF catalyzes an ammonia-dependent reaction that uses ammonia as a nitrogen donor in the place of the physiological donor glutamine [Klem93]. The kinetics of HisFH have been modeled [Demin04].

HisFH is a 1:1 dimer of HisF and HisH [Klem93]. The critical residues involved in subunit interaction in general and in the specific case of cooperation of the two active sites have been examined [Klem01, Myers05].

Credits:
Imported from EcoCyc 16-Sep-2014 by Paley S , SRI International


Enzymatic reaction of: imidazole glycerol phosphate synthase

EC Number: 2.4.2.-

phosphoribulosylformimino-AICAR-P + L-glutamine <=> L-glutamate + D-erythro-imidazole-glycerol-phosphate + 5-amino-1-(5-phospho-D-ribosyl)imidazole-4-carboxamide + 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.

The reaction is irreversible in the direction shown.

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

Credits:
Imported from EcoCyc 16-Sep-2014 by Paley S , SRI International

Summary:
The kM for ammonia in the variant reaction catalyzed by isolated HisF is 17 mM [Klem93].

Inhibitors (Unknown Mechanism): Mg2+ [Klem93] , Mn2+ [Klem93]

Kinetic Parameters:

Substrate
Km (μM)
Citations
L-glutamine
240.0
[Klem93]
phosphoribulosylformimino-AICAR-P
28.1
[Klem93]


Sequence Features

Feature Class Location Citations Comment
Mutagenesis-Variant 5
[Klem01, UniProt11]
Alternate sequence: H; UniProt: Loss of IGP synthase activity. Weak IGP synthase activity and reduced hisH activity in vitro.
Alternate sequence: A; UniProt: Loss of activity.
Active-Site 11
[UniProt10a]
UniProt: Non-Experimental Qualifier: potential;
Mutagenesis-Variant 46
[Klem01, UniProt11]
Alternate sequence: G; UniProt: Loss of IGP synthase activity. Weak IGP synthase and hisH activities in vitro.
Alternate sequence: A; UniProt: Loss of activity.
Mutagenesis-Variant 123
[Klem01, UniProt11]
Alternate sequence: R; UniProt: Loss of IGP synthase activity. Weak hisH activity in vitro.
Alternate sequence: A; UniProt: Decrease in activity.
Mutagenesis-Variant 124
[Klem01, UniProt11]
Alternate sequence: R; UniProt: Loss of IGP synthase activity. Weak hisH activity in vitro.
Alternate sequence: A; UniProt: No change in activity.
Active-Site 130
[UniProt10a]
UniProt: Non-Experimental Qualifier: potential;

History:
10/20/97 Gene b2025 from Blattner lab Genbank (v. M52) entry merged into EcoCyc gene EG10448; confirmed by SwissProt match.


References

Demin04: Demin OV, Goryanin II, Dronov S, Lebedeva GV (2004). "Kinetic model of imidazologlycerol-phosphate synthetase from Escherichia coli." Biochemistry (Mosc) 69(12);1324-35. PMID: 15627387

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

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."

Klem01: Klem TJ, Chen Y, Davisson VJ (2001). "Subunit interactions and glutamine utilization by Escherichia coli imidazole glycerol phosphate synthase." J Bacteriol 183(3);989-96. PMID: 11208798

Klem93: Klem TJ, Davisson VJ (1993). "Imidazole glycerol phosphate synthase: the glutamine amidotransferase in histidine biosynthesis." Biochemistry 1993;32(19);5177-86. PMID: 8494895

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

Myers05: Myers RS, Amaro RE, Luthey-Schulten ZA, Davisson VJ (2005). "Reaction coupling through interdomain contacts in imidazole glycerol phosphate synthase." Biochemistry 44(36);11974-85. PMID: 16142895

ODonoghue: O'Donoghue P, Amaro RE, Luthey-Schulten Z "On the structure of hisH: protein structure prediction in the context of structural and functional genomics." J Struct Biol 134(2-3);257-68. PMID: 11551184

UniProt10a: UniProt Consortium (2010). "UniProt version 2010-07 released on 2010-06-15 00:00:00." Database.

UniProt11: UniProt Consortium (2011). "UniProt version 2011-06 released on 2011-06-30 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."


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
Page generated by SRI International Pathway Tools version 18.5 on Fri Nov 28, 2014, BIOCYC14B.