Metabolic Modeling Tutorial
discounted EARLY registration ends Dec 31, 2014
Metabolic Modeling Tutorial
discounted EARLY registration ends Dec 31, 2014
Metabolic Modeling Tutorial
discounted EARLY registration ends Dec 31, 2014
Metabolic Modeling Tutorial
discounted EARLY registration ends Dec 31, 2014
Metabolic Modeling Tutorial
discounted EARLY registration ends Dec 31, 2014
twitter

MetaCyc Enzyme: GTP cyclohydrolase I

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

Species: Escherichia coli K-12 substr. MG1655

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

Summary:
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, Schramek01, 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, Lee02a]. 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]

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

Molecular Weight of Multimer: 250.0 kD (experimental) [Lee02a]

pI: 7.28

Unification Links: ASAP:ABE-0007117 , CGSC:32718 , 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: ?

GO Terms:

Biological Process: GO:0008616 - queuosine biosynthetic process Inferred from experiment [Phillips08]
GO:0006730 - one-carbon metabolic process Inferred by computational analysis [UniProtGOA11, GOA06]
GO:0008152 - metabolic process Inferred by computational analysis [UniProtGOA11]
GO:0035998 - 7,8-dihydroneopterin 3'-triphosphate biosynthetic process Inferred by computational analysis [UniProtGOA12]
GO:0046654 - tetrahydrofolate biosynthetic process Inferred by computational analysis [GOA06, GOA01]
Molecular Function: GO:0003934 - GTP cyclohydrolase I activity Inferred from experiment Inferred by computational analysis [GOA06, GOA01a, GOA01, Nar95]
GO:0005525 - GTP binding Inferred from experiment Inferred by computational analysis [UniProtGOA11, Yim76]
GO:0008270 - zinc ion binding Inferred from experiment Inferred by computational analysis [GOA06, Auerbach00]
GO:0000166 - nucleotide binding Inferred by computational analysis [UniProtGOA11]
GO:0003824 - catalytic activity Inferred by computational analysis [UniProtGOA11]
GO:0016787 - hydrolase activity Inferred by computational analysis [UniProtGOA11]
GO:0046872 - metal ion binding Inferred by computational analysis [UniProtGOA11]
Cellular Component: GO:0005737 - cytoplasm Inferred from experiment Inferred by computational analysis [GOA01, 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

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


Enzymatic reaction of: GTP cyclohydrolase

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

EC Number: 3.5.4.16

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 1]:

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

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

Summary:
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 2]

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:

Substrate
Km (μM)
Citations
GTP
100.0
[Schoedon92]

T(opt): 42 °C [BRENDA14, Burg68], 60 °C [Lee02a]

pH(opt): 8 [BRENDA14, Burg68], 8.5 [Lee02a]


Sequence Features

Feature Class Location Citations Comment
Cleavage-of-Initial-Methionine 1
[UniProt10]
UniProt: Removed;
Chain 2 -> 222
[UniProt09]
UniProt: GTP cyclohydrolase 1;
Metal-Binding-Site 111
[UniProt10]
UniProt: Zinc;
Metal-Binding-Site 114
[UniProt10]
UniProt: Zinc;
Acetylation-Modification 137
[Yu08]
 
Metal-Binding-Site 182
[UniProt10]
UniProt: Zinc;

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


References

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

BRENDA14: BRENDA team (2014). "Imported from BRENDA version existing on Aug 2014." http://www.brenda-enzymes.org.

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

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."

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

Lee02a: 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

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

Schramek01: 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.

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 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


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 Sat Nov 22, 2014, biocyc13.