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Escherichia coli K-12 substr. MG1655 Enzyme: GTP cyclohydrolase I

Gene: folE Accession Numbers: EG11375 (EcoCyc), b2153, ECK2146

Regulation Summary Diagram: ?

Regulation summary diagram for folE

Subunit composition of GTP cyclohydrolase I = [FolE]10
         GTP cyclohydrolase I monomer = FolE

GTP cyclohydrolase I is an allosteric enzyme that catalyzes the first step in the biosynthesis of tetrahydrofolate [Burg68, Katzenmeier91, Schoedon92] and the modified base queuosine [Phillips08]. The enzymatic reaction has a complex mechanism and appears to encompass four steps, with the intermediates being enzyme-bound. Detailed studies of the kinetics and reaction mechanism of the enzyme have been performed [Nar95, Schramek01a, Schramek02, Rebelo03].

Crystal structures and electron microscope observations of GTP cyclohydrolase I have shown a homodecamer that forms a torus [Schmid92, Nar95a, Meining95, Rebelo03]. The active site appears to be located between dimers, and the active enzyme is composed of a pentamer of five dimers [Nar95, Lee02c]. A catalytically active zinc ion is coordinated by C110, C181, and H113 [Rebelo03]. Each polypeptide seems to contain one GTP binding site [Yim76, Katzenmeier91].

FolE is sensitive to oxidative stress [Leichert04].

A folE deletion mutant lacks the queuosine ribonucleoside in tRNAs, indicating that folE is required for preQ0 biosynthesis from GTP [Phillips08]. folE gene expression is repressed by MetJ [Marincs06].

FolE: [Ritz93]

Locations: cytosol

Map Position: [2,241,006 <- 2,241,674] (48.3 centisomes, 174°)
Length: 669 bp / 222 aa

Molecular Weight of Polypeptide: 24.831 kD (from nucleotide sequence)

Molecular Weight of Multimer: 250.0 kD (experimental) [Lee02c]

pI: 7.28

Unification Links: ASAP:ABE-0007117 , CGSC:32718 , DIP:DIP-9676N , EchoBASE:EB1349 , EcoGene:EG11375 , EcoliWiki:b2153 , EcoO157Cyc:FOLE-MONOMER , Mint:MINT-6732927 , OU-Microarray:b2153 , PortEco:folE , Pride:P0A6T5 , Protein Model Portal:P0A6T5 , RefSeq:NP_416658 , RegulonDB:EG11375 , SMR:P0A6T5 , String:511145.b2153 , UniProt:P0A6T5

Relationship Links: InterPro:IN-FAMILY:IPR001474 , InterPro:IN-FAMILY:IPR018234 , InterPro:IN-FAMILY:IPR020602 , Panther:IN-FAMILY:PTHR11109 , PDB:Structure:1A8R , PDB:Structure:1A9C , PDB:Structure:1FBX , PDB:Structure:1GTP , PDB:Structure:1N3R , PDB:Structure:1N3S , PDB:Structure:1N3T , Pfam:IN-FAMILY:PF01227 , Prosite:IN-FAMILY:PS00859 , Prosite:IN-FAMILY:PS00860

Gene-Reaction Schematic: ?

Gene-Reaction Schematic

Genetic Regulation Schematic: ?

Genetic regulation schematic for folE

GO Terms:

Biological Process: GO:0008616 - queuosine biosynthetic process Inferred from experiment [Phillips08]
GO:0006729 - tetrahydrobiopterin biosynthetic process Inferred by computational analysis [Gaudet10]
GO:0006730 - one-carbon metabolic process Inferred by computational analysis [UniProtGOA11a, GOA06]
GO:0008152 - metabolic process Inferred by computational analysis [UniProtGOA11a]
GO:0035998 - 7,8-dihydroneopterin 3'-triphosphate biosynthetic process Inferred by computational analysis [UniProtGOA12]
GO:0046654 - tetrahydrofolate biosynthetic process Inferred by computational analysis [GOA06, GOA01a]
Molecular Function: GO:0003934 - GTP cyclohydrolase I activity Inferred from experiment Inferred by computational analysis [GOA06, GOA01, GOA01a, Nar95]
GO:0005525 - GTP binding Inferred from experiment Inferred by computational analysis [UniProtGOA11a, Yim76]
GO:0008270 - zinc ion binding Inferred from experiment Inferred by computational analysis [GOA06, Auerbach00]
GO:0000166 - nucleotide binding Inferred by computational analysis [UniProtGOA11a]
GO:0003824 - catalytic activity Inferred by computational analysis [UniProtGOA11a]
GO:0016787 - hydrolase activity Inferred by computational analysis [UniProtGOA11a]
GO:0046872 - metal ion binding Inferred by computational analysis [UniProtGOA11a]
Cellular Component: GO:0005737 - cytoplasm Inferred from experiment Inferred by computational analysis [GOA01a, Yim76, Burg68]
GO:0005829 - cytosol Inferred from experiment Inferred by computational analysis [DiazMejia09, Ishihama08]
GO:0043234 - protein complex Inferred from experiment [Yim76, Nar95a]

MultiFun Terms: metabolism biosynthesis of building blocks cofactors, small molecule carriers folic acid

Essentiality data for folE knockouts: ?

Growth Medium Growth? T (°C) O2 pH Osm/L Growth Observations
LB Lennox No 37 Aerobic 7   No [Baba06, Comment 1]

Last-Curated ? 25-Apr-2011 by Keseler I , SRI International

Enzymatic reaction of: GTP cyclohydrolase

Synonyms: GTP 7,8-8,9-dihydrolase

EC Number:

GTP + H2O <=> formate + 7,8-dihydroneopterin 3'-triphosphate + H+

The reaction direction shown, that is, A + B ↔ C + D versus C + D ↔ A + B, is in accordance with the Enzyme Commission system.

The reaction is favored in the direction shown.

Alternative Substrates [Comment 2]:

In Pathways: superpathway of chorismate metabolism , superpathway of tetrahydrofolate biosynthesis , 6-hydroxymethyl-dihydropterin diphosphate biosynthesis I , preQ0 biosynthesis , tetrahydromonapterin biosynthesis

Purification of the enzyme reported in [Burg68, Yim76] used E. coli B. The source of the enzyme reported in [Schoedon92] is unclear.

Cofactors or Prosthetic Groups: Zn2+ [Auerbach00]

Activators (Unknown Mechanism): K+ [Schoedon92]

Inhibitors (Allosteric): tetrahydrobiopterin [Schoedon92, Comment 3]

Inhibitors (Competitive): guanosine tetraphosphate (Kic = 0.13µM) [Yim76] , ATP (Kic = 0.25µM) [Yim76] , dGTP (Kic = 0.24µM) [Yim76] , GDP (Kic = 1.5µM) [Yim76] , UTP (Kic = 2.9µM) [Yim76] , dTTP (Kic = 1.6µM) [Yim76] , ADP (Kic = 10µM) [Yim76]

Inhibitors (Uncompetitive): phosphate [Yim76]

Kinetic Parameters:

Km (μM)

T(opt): 42 °C [BRENDA14, Burg68], 60 °C [Lee02c]

pH(opt): 8 [BRENDA14, Burg68], 8.5 [Lee02c]

Sequence Features

Protein sequence of GTP cyclohydrolase I monomer with features indicated

Feature Class Location Citations Comment
Cleavage-of-Initial-Methionine 1
[Schoedon92, Link97, UniProt10a, Katzenmeier91]
UniProt: Removed;
Chain 2 -> 222
UniProt: GTP cyclohydrolase 1;
Metal-Binding-Site 111
UniProt: Zinc.
Metal-Binding-Site 114
UniProt: Zinc.
Acetylation-Modification 137
Metal-Binding-Site 182
UniProt: Zinc.

Gene Local Context (not to scale): ?

Gene local context diagram

Transcription Unit:

Transcription-unit diagram


10/20/97 Gene b2153 from Blattner lab Genbank (v. M52) entry merged into EcoCyc gene EG11375; confirmed by SwissProt match.


Auerbach00: Auerbach G, Herrmann A, Bracher A, Bader G, Gutlich M, Fischer M, Neukamm M, Garrido-Franco M, Richardson J, Nar H, Huber R, Bacher A (2000). "Zinc plays a key role in human and bacterial GTP cyclohydrolase I." Proc Natl Acad Sci U S A 97(25);13567-72. PMID: 11087827

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

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

Burg68: Burg AW, Brown GM (1968). "The biosynthesis of folic acid. 8. Purification and properties of the enzyme that catalyzes the production of formate from carbon atom 8 of guanosine triphosphate." J Biol Chem 1968;243(9);2349-58. PMID: 4296838

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

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

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."

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

Katzenmeier91: Katzenmeier G, Schmid C, Kellermann J, Lottspeich F, Bacher A (1991). "Biosynthesis of tetrahydrofolate. Sequence of GTP cyclohydrolase I from Escherichia coli." Biol Chem Hoppe Seyler 1991;372(11);991-7. PMID: 1665332

Lee02c: Lee S, Ahn C, Park E, Hwang DS, Yim J (2002). "Biochemical characterization of oligomerization of Escherichia coli GTP cyclohydrolase I." J Biochem Mol Biol 35(3);255-61. PMID: 12297008

Leichert04: Leichert LI, Jakob U (2004). "Protein thiol modifications visualized in vivo." PLoS Biol 2(11);e333. PMID: 15502869

Link97: Link AJ, Robison K, Church GM (1997). "Comparing the predicted and observed properties of proteins encoded in the genome of Escherichia coli K-12." Electrophoresis 18(8);1259-313. PMID: 9298646

Marincs06: Marincs F, Manfield IW, Stead JA, McDowall KJ, Stockley PG (2006). "Transcript analysis reveals an extended regulon and the importance of protein-protein co-operativity for the Escherichia coli methionine repressor." Biochem J 396(2);227-34. PMID: 16515535

Meining95: Meining W, Bacher A, Bachmann L, Schmid C, Weinkauf S, Huber R, Nar H (1995). "Elucidation of crystal packing by X-ray diffraction and freeze-etching electron microscopy. Studies on GTP cyclohydrolase I of Escherichia coli." J Mol Biol 253(1);208-18. PMID: 7473713

Nar95: Nar H, Huber R, Auerbach G, Fischer M, Hosl C, Ritz H, Bracher A, Meining W, Eberhardt S, Bacher A (1995). "Active site topology and reaction mechanism of GTP cyclohydrolase I." Proc Natl Acad Sci U S A 92(26);12120-5. PMID: 8618856

Nar95a: Nar H, Huber R, Meining W, Schmid C, Weinkauf S, Bacher A (1995). "Atomic structure of GTP cyclohydrolase I." Structure 3(5);459-66. PMID: 7663943

Phillips08: Phillips G, El Yacoubi B, Lyons B, Alvarez S, Iwata-Reuyl D, de Crecy-Lagard V (2008). "Biosynthesis of 7-deazaguanosine-modified tRNA nucleosides: a new role for GTP cyclohydrolase I." J Bacteriol 190(24):7876-84. PMID: 18931107

Rebelo03: Rebelo J, Auerbach G, Bader G, Bracher A, Nar H, Hosl C, Schramek N, Kaiser J, Bacher A, Huber R, Fischer M (2003). "Biosynthesis of pteridines. Reaction mechanism of GTP cyclohydrolase I." J Mol Biol 326(2);503-16. PMID: 12559918

Ritz93: Ritz H, Keller G, Richter G, Katzenmeier G, Bacher A (1993). "Location of the gene coding for GTP cyclohydrolase I on the physical map of Escherichia coli." J Bacteriol 175(5);1553. PMID: 8444819

Schmid92: Schmid C, Ladenstein R, Luecke H, Huber R, Bacher A (1992). "Crystallization and preliminary crystallographic characterization of GTP cyclohydrolase I from Escherichia coli." J Mol Biol 226(4);1279-81. PMID: 1518056

Schoedon92: Schoedon G, Redweik U, Frank G, Cotton RG, Blau N (1992). "Allosteric characteristics of GTP cyclohydrolase I from Escherichia coli." Eur J Biochem 1992;210(2);561-8. PMID: 1459137

Schramek01a: Schramek N, Bracher A, Bacher A (2001). "Ring opening is not rate-limiting in the GTP cyclohydrolase I reaction." J Biol Chem 276(4);2622-6. PMID: 11056154

Schramek02: Schramek N, Bracher A, Fischer M, Auerbach G, Nar H, Huber R, Bacher A (2002). "Reaction mechanism of GTP cyclohydrolase I: single turnover experiments using a kinetically competent reaction intermediate." J Mol Biol 316(3);829-37. PMID: 11866535

UniProt09: UniProt Consortium (2009). "UniProt version 15.8 released on 2009-10-01 00:00:00." Database.

UniProt10a: UniProt Consortium (2010). "UniProt version 2010-11 released on 2010-11-02 00:00:00." Database.

UniProt15: UniProt Consortium (2015). "UniProt version 2015-01 released on 2015-01-16 00:00:00." Database.

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."

Yim76: Yim JJ, Brown GM (1976). "Characteristics of guanosine triphosphate cyclohydrolase I purified from Escherichia coli." J Biol Chem 1976;251(16);5087-94. PMID: 821948

Yu08: Yu BJ, Kim JA, Moon JH, Ryu SE, Pan JG (2008). "The diversity of lysine-acetylated proteins in Escherichia coli." J Microbiol Biotechnol 18(9);1529-36. PMID: 18852508

Other References Related to Gene Regulation

Durand10: Durand S, Storz G (2010). "Reprogramming of anaerobic metabolism by the FnrS small RNA." Mol Microbiol 75(5);1215-31. PMID: 20070527

Huerta03: Huerta AM, Collado-Vides J (2003). "Sigma70 promoters in Escherichia coli: specific transcription in dense regions of overlapping promoter-like signals." J Mol Biol 333(2);261-78. PMID: 14529615

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