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discounted EARLY registration ends Dec 31, 2014
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12/28 - 12/31
for maintenance.
Metabolic Modeling Tutorial
discounted EARLY registration ends Dec 31, 2014
BioCyc websites MAYBE down
12/28 - 12/31
for maintenance.
Metabolic Modeling Tutorial
discounted EARLY registration ends Dec 31, 2014
BioCyc websites MAYBE down
12/28 - 12/31
for maintenance.
Metabolic Modeling Tutorial
discounted EARLY registration ends Dec 31, 2014
BioCyc websites MAYBE down
12/28 - 12/31
for maintenance.
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MetaCyc Pathway: 6-hydroxymethyl-dihydropterin diphosphate biosynthesis I

Enzyme View:

This view shows enzymes only for those organisms listed below, in the list of taxa known to possess the pathway. If an enzyme name is shown in bold, there is experimental evidence for this enzymatic activity.

Superclasses: Biosynthesis Cofactors, Prosthetic Groups, Electron Carriers Biosynthesis Vitamins Biosynthesis Folate Biosynthesis 6-Hydroxymethyl-Dihydropterin Diphosphate Biosynthesis

Some taxa known to possess this pathway include ? : Arabidopsis thaliana col , Escherichia coli K-12 substr. MG1655 , Lactococcus lactis , Pisum sativum , Saccharomyces cerevisiae , Solanum lycopersicum , Spinacia oleracea

Expected Taxonomic Range: Bacteria , Fungi , Viridiplantae

Summary:
(2-amino-4-hydroxy-7,8-dihydropteridin-6-yl)methyl diphosphate (6-hydroxymethyl-dihydropterin diphosphate) is the pterin precursor for the biosynthesis of several important cofactors, including tetrahydropteroyl mono-L-glutamate, methanopterin and sarcinapterin. The compound is always synthesized from GTP, but the enzymes involve may differ among organisms.

This pathway, which is found in bacteria, fungi and plants, starts with GTP cyclohydrolase I, an enzyme that converts GTP into 7,8-dihydroneopterin 3'-triphosphate. The triphosphate motif is removed in a process that is still not completely understood, and the resulting 7,8-dihydroneopterin is converted to 6-hydroxymethyl-7,8-dihydropterin by dihydroneopterin aldolase (FolB).

In plants the pterin moiety is formed from GTP in the cytosol.

Superpathways: superpathway of tetrahydrofolate biosynthesis , superpathway of chorismate metabolism , superpathway of tetrahydrofolate biosynthesis and salvage

Variants: 6-hydroxymethyl-dihydropterin diphosphate biosynthesis II (archaea) , 6-hydroxymethyl-dihydropterin diphosphate biosynthesis III (Chlamydia)

Unification Links: EcoCyc:PWY-6147

Credits:
Created 05-Mar-2009 by Caspi R , SRI International


References

Basset02: Basset G, Quinlivan EP, Ziemak MJ, Diaz De La Garza R, Fischer M, Schiffmann S, Bacher A, Gregory JF, Hanson AD (2002). "Folate synthesis in plants: the first step of the pterin branch is mediated by a unique bimodular GTP cyclohydrolase I." Proc Natl Acad Sci U S A 99(19);12489-94. PMID: 12221287

Other References Related to Enzymes, Genes, Subpathways, and Substrates of this Pathway

Adams14: Adams NE, Thiaville JJ, Proestos J, Juarez-Vazquez AL, McCoy AJ, Barona-Gomez F, Iwata-Reuyl D, de Crecy-Lagard V, Maurelli AT (2014). "Promiscuous and adaptable enzymes fill "holes" in the tetrahydrofolate pathway in Chlamydia species." MBio 5(4). PMID: 25006229

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

Babitzke92: Babitzke P, Gollnick P, Yanofsky C (1992). "The mtrAB operon of Bacillus subtilis encodes GTP cyclohydrolase I (MtrA), an enzyme involved in folic acid biosynthesis, and MtrB, a regulator of tryptophan biosynthesis." J Bacteriol 174(7);2059-64. PMID: 1551827

Ballantine94: Ballantine SP, Volpe F, Delves CJ (1994). "The hydroxymethyldihydropterin pyrophosphokinase domain of the multifunctional folic acid synthesis Fas protein of Pneumocystis carinii expressed as an independent enzyme in Escherichia coli: refolding and characterization of the recombinant enzyme." Protein Expr Purif 5(4);371-8. PMID: 7950384

Bauer04: Bauer S, Schott AK, Illarionova V, Bacher A, Huber R, Fischer M (2004). "Biosynthesis of tetrahydrofolate in plants: crystal structure of 7,8-dihydroneopterin aldolase from Arabidopsis thaliana reveals a novel aldolase class." J Mol Biol 339(4);967-79. PMID: 15165863

Bermingham00: Bermingham A, Bottomley JR, Primrose WU, Derrick JP (2000). "Equilibrium and kinetic studies of substrate binding to 6-hydroxymethyl-7,8-dihydropterin pyrophosphokinase from Escherichia coli." J Biol Chem 275(24);17962-7. PMID: 10751386

Bermingham02: Bermingham A, Derrick JP (2002). "The folic acid biosynthesis pathway in bacteria: evaluation of potential for antibacterial drug discovery." Bioessays 24(7);637-48. PMID: 12111724

Blaszczyk00: Blaszczyk J, Shi G, Yan H, Ji X (2000). "Catalytic center assembly of HPPK as revealed by the crystal structure of a ternary complex at 1.25 A resolution." Structure 8(10);1049-58. PMID: 11080626

Blaszczyk03: Blaszczyk J, Li Y, Shi G, Yan H, Ji X (2003). "Dynamic roles of arginine residues 82 and 92 of Escherichia coli 6-hydroxymethyl-7,8-dihydropterin pyrophosphokinase: crystallographic studies." Biochemistry 42(6);1573-80. PMID: 12578370

Blaszczyk04: Blaszczyk J, Li Y, Wu Y, Shi G, Ji X, Yan H (2004). "Essential roles of a dynamic loop in the catalysis of 6-hydroxymethyl-7,8-dihydropterin pyrophosphokinase." Biochemistry 43(6);1469-77. PMID: 14769023

Blaszczyk04a: Blaszczyk J, Shi G, Li Y, Yan H, Ji X (2004). "Reaction trajectory of pyrophosphoryl transfer catalyzed by 6-hydroxymethyl-7,8-dihydropterin pyrophosphokinase." Structure (Camb) 12(3);467-75. PMID: 15016362

Bolotin01: Bolotin A, Wincker P, Mauger S, Jaillon O, Malarme K, Weissenbach J, Ehrlich SD, Sorokin A (2001). "The complete genome sequence of the lactic acid bacterium Lactococcus lactis ssp. lactis IL1403." Genome Res 11(5);731-53. PMID: 11337471

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

Brown71: Brown GM (1971). "The biosynthesis of pteridines." Adv Enzymol Relat Areas Mol Biol 1971;35;35-77. PMID: 4361155

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

deCrecyLagard12: de Crecy-Lagard V, Phillips G, Grochowski LL, El Yacoubi B, Jenney F, Adams MW, Murzin AG, White RH (2012). "Comparative genomics guided discovery of two missing archaeal enzyme families involved in the biosynthesis of the pterin moiety of tetrahydromethanopterin and tetrahydrofolate." ACS Chem Biol 7(11);1807-16. PMID: 22931285

Derrick08: Derrick JP (2008). "The structure and mechanism of 6-hydroxymethyl-7,8-dihydropterin pyrophosphokinase." Vitam Horm 79;411-33. PMID: 18804704

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

Dobrzanska02: Dobrzanska M, Szurmak B, Wyslouch-Cieszynska A, Kraszewska E (2002). "Cloning and characterization of the first member of the Nudix family from Arabidopsis thaliana." J Biol Chem 277(52);50482-6. PMID: 12399474

El06: El Yacoubi B, Bonnett S, Anderson JN, Swairjo MA, Iwata-Reuyl D, de Crecy-Lagard V (2006). "Discovery of a new prokaryotic type I GTP cyclohydrolase family." J Biol Chem 281(49);37586-93. PMID: 17032654

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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 Thu Dec 25, 2014, BIOCYC14B.