If an enzyme name is shown in bold, there is experimental evidence for this enzymatic activity.
Locations of Mapped Genes:
|Superclasses:||Biosynthesis → Cofactors, Prosthetic Groups, Electron Carriers Biosynthesis → Vitamins Biosynthesis → Folate Biosynthesis → 6-Hydroxymethyl-Dihydropterin Diphosphate Biosynthesis|
Reduced folate cofactors are required for the syntheses of various essential cell nutrients. E. coli and other microorganisms must synthesize folates de novo as they lack the transport pathway to take up folate cofactors.
(2-amino-4-hydroxy-7,8-dihydropteridin-6-yl)methyl diphosphate is the pterin precursor for the biosynthesis of tetrahydropteroyl mono-L-glutamate. This pterin is synthesized from GTP in a pathway that starts with GTP cyclohydrolase I, which converts GTP into 7,8-dihydroneopterin 3'-triphosphate. The NudB pyrophosphohydrolase then generates 7,8-dihydroneopterin 3'-phosphate. The remaining phosphate group may be removed by one or more non-specific phosphatases. The resulting 7,8-dihydroneopterin is fist converted to 6-hydroxymethyl-7,8-dihydropterin by dihydroneopterin aldolase and subsequently phosphorylated to (2-amino-4-hydroxy-7,8-dihydropteridin-6-yl)methyl diphosphate by FolK.
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
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
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
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
Blaszczyk14: Blaszczyk J, Lu Z, Li Y, Yan H, Ji X (2014). "Crystallographic and molecular dynamics simulation analysis of Escherichia coli dihydroneopterin aldolase." Cell Biosci 4(1);52. PMID: 25264482
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
Eydallin07: Eydallin G, Viale AM, Moran-Zorzano MT, Munoz FJ, Montero M, Baroja-Fernandez E, Pozueta-Romero J (2007). "Genome-wide screening of genes affecting glycogen metabolism in Escherichia coli K-12." FEBS Lett 581(16);2947-53. PMID: 17543954
Gabelli07: Gabelli SB, Bianchet MA, Xu W, Dunn CA, Niu ZD, Amzel LM, Bessman MJ (2007). "Structure and function of the E. coli dihydroneopterin triphosphate pyrophosphatase: a Nudix enzyme involved in folate biosynthesis." Structure 15(8);1014-22. PMID: 17698004
Garcon04: Garcon A, Bermingham A, Lian LY, Derrick JP (2004). "Kinetic and structural characterization of a product complex of 6-hydroxymethyl-7,8-dihydropterin pyrophosphokinase from Escherichia coli." Biochem J 380(Pt 3);867-73. PMID: 15018613
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