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Escherichia coli K-12 substr. MG1655 Pathway: superpathway of adenosine nucleotides de novo biosynthesis II
Traceable author statement to experimental support

Pathway diagram: superpathway of adenosine nucleotides de novo biosynthesis II

If an enzyme name is shown in bold, there is experimental evidence for this enzymatic activity.

Locations of Mapped Genes:

Schematic showing all replicons, marked with selected genes

Genetic Regulation Schematic

Genetic regulation schematic for superpathway of adenosine nucleotides de novo biosynthesis II

Superclasses: BiosynthesisNucleosides and Nucleotides BiosynthesisPurine Nucleotide BiosynthesisPurine Nucleotides De Novo Biosynthesis

General Background

De novo biosynthesis of purines starts with the synthesis of IMP which can be converted to all other purines. In E. coli IMP is synthesized in a total of 11 enzymatic reactions in which the purine ring is formed by stepwise addition of small molecules to 5-phospho-α-D-ribose-1-phosphate (PRPP). The first five reactions are shown in pathways 5-aminoimidazole ribonucleotide biosynthesis I and 5-aminoimidazole ribonucleotide biosynthesis II which illustrate the alternative use of two phosphoribosylglycinamide formyltransferases encoded by purN and purT. The last six reactions leading to IMP are shown in pathway inosine-5'-phosphate biosynthesis I. IMP can then be converted to guanosine nucleotides as shown in pathway superpathway of guanosine nucleotides de novo biosynthesis II, or adenosine nucleotides as shown in this pathway.

About This Pathway

IMP is converted to adenylo-succinate by the enzyme adenylosuccinate synthetase (PurA) and the latter compound is converted to the first adenosine nucleotide, AMP, by the adenylosuccinate lyase activity of PurB.

AMP is then converted to ADP and subsequently to ATP. The AMP to ADP conversion is catalyzed by adenylate kinase, a specific nucleoside monophosphate kinase. Numerous reactions can convert ADP to ATP and they can be found in multiple pathways including fueling pathways such as anaerobic respiration, TCA-aerobic respiration, fermentation, and glycolysis. However, a major source for this conversion is the ATP synthase / thiamin triphosphate synthase complex, which is membrane bound and utilizes a proton gradient across membranes to phosphorylate ADP. This is the reaction depicted in this pathway.

ADP can also be converted to the deoxy form dADP by either ribonucleoside diphosphate reductase 1 (NrdAB) or ribonucleoside-diphosphate reductase 2 (NrdEF). dADP is converted to dATP by nucleoside diphosphate kinase (Ndk). Under strictly anaerobic conditions, the ATP reductase activity of the class III ribonucleotide reductase NrdD can convert ATP to its deoxy form.

In bacteria, genetic studies have indicated that the majority of de novo purine biosynthetic genes are unlinked, but may act as a single unit of regulation controlled by the PurR repressor protein [Meng90].

Review: Jensen, K.F., G. Dandanell, B. Hove-Jensen, and M. Willemoes (2008) "Nucleotides, Nucleosides and Nucleobases" EcoSal 3.6.2 [ECOSAL]

Superpathways: superpathway of purine nucleotides de novo biosynthesis II, superpathway of histidine, purine, and pyrimidine biosynthesis

Subpathways: adenosine deoxyribonucleotides de novo biosynthesis II, adenosine ribonucleotides de novo biosynthesis

Variants: superpathway of guanosine nucleotides de novo biosynthesis II

Created 13-Jan-2009 by Caspi R, SRI International
Last-Curated 03-Jan-2012 by Fulcher C, SRI International


ECOSAL: "Escherichia coli and Salmonella: Cellular and Molecular Biology." Online edition.

Meng90: Meng LM, Kilstrup M, Nygaard P (1990). "Autoregulation of PurR repressor synthesis and involvement of purR in the regulation of purB, purC, purL, purMN and guaBA expression in Escherichia coli." Eur J Biochem 1990;187(2);373-9. PMID: 2404765

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

Abrahams94: Abrahams JP, Leslie AG, Lutter R, Walker JE (1994). "Structure at 2.8 A resolution of F1-ATPase from bovine heart mitochondria." Nature 370(6491);621-8. PMID: 8065448

Aksimentiev04: Aksimentiev A, Balabin IA, Fillingame RH, Schulten K (2004). "Insights into the molecular mechanism of rotation in the Fo sector of ATP synthase." Biophys J 86(3);1332-44. PMID: 14990464

Allard92: Allard P, Kuprin S, Shen B, Ehrenberg A (1992). "Binding of the competitive inhibitor dCDP to ribonucleoside-diphosphate reductase from Escherichia coli studied by 1H NMR. Different properties of the large protein subunit and the holoenzyme." Eur J Biochem 1992;208(3);635-42. PMID: 1396671

Almaula95: Almaula N, Lu Q, Delgado J, Belkin S, Inouye M (1995). "Nucleoside diphosphate kinase from Escherichia coli." J Bacteriol 177(9);2524-9. PMID: 7730286

alShawi92: al-Shawi MK, Senior AE (1992). "Catalytic sites of Escherichia coli F1-ATPase. Characterization of unisite catalysis at varied pH." Biochemistry 31(3);878-85. PMID: 1531027

Andersson99: Andersson ME, Hogbom M, Rinaldo-Matthis A, Andersson KK, Sjoberg BM, Nordlund P (1999). "The Crystal Structure of an Azide Complex of the Diferrous R2 Subunit of Ribonucleotide Reductase Displays a Novel Carboxylate Shift with Important Mechanistic Implications for Diiron-Catalyzed Oxygen Activation." J. Am. Chem. Soc. 121: 2346-2352.

Andrews11: Andrews SC (2011). "Making DNA without iron - induction of a manganese-dependent ribonucleotide reductase in response to iron starvation." Mol Microbiol 80(2);286-9. PMID: 21371140

Angevine03: Angevine CM, Herold KA, Fillingame RH (2003). "Aqueous access pathways in subunit a of rotary ATP synthase extend to both sides of the membrane." Proc Natl Acad Sci U S A 100(23);13179-83. PMID: 14595019

Angevine07: Angevine CM, Herold KA, Vincent OD, Fillingame RH (2007). "Aqueous access pathways in ATP synthase subunit a. Reactivity of cysteine substituted into transmembrane helices 1, 3, and 5." J Biol Chem 282(12);9001-7. PMID: 17234633

Arifuzzaman06: Arifuzzaman M, Maeda M, Itoh A, Nishikata K, Takita C, Saito R, Ara T, Nakahigashi K, Huang HC, Hirai A, Tsuzuki K, Nakamura S, Altaf-Ul-Amin M, Oshima T, Baba T, Yamamoto N, Kawamura T, Ioka-Nakamichi T, Kitagawa M, Tomita M, Kanaya S, Wada C, Mori H (2006). "Large-scale identification of protein-protein interaction of Escherichia coli K-12." Genome Res 16(5);686-91. PMID: 16606699

Aris85: Aris JP, Klionsky DJ, Simoni RD (1985). "The Fo subunits of the Escherichia coli F1Fo-ATP synthase are sufficient to form a functional proton pore." J Biol Chem 260(20);11207-15. PMID: 2863271

Artin09: Artin E, Wang J, Lohman GJ, Yokoyama K, Yu G, Griffin RG, Bar G, Stubbe J (2009). "Insight into the mechanism of inactivation of ribonucleotide reductase by gemcitabine 5'-diphosphate in the presence or absence of reductant." Biochemistry 48(49);11622-9. PMID: 19899770

Assarsson01: Assarsson M, Andersson ME, Hogbom M, Persson BO, Sahlin M, Barra AL, Sjoberg BM, Nordlund P, Graslund A (2001). "Restoring proper radical generation by azide binding to the iron site of the E238A mutant R2 protein of ribonucleotide reductase from Escherichia coli." J Biol Chem 276(29);26852-9. PMID: 11328804

Bairoch93: Bairoch A, Boeckmann B (1993). "The SWISS-PROT protein sequence data bank, recent developments." Nucleic Acids Res. 21:3093-3096. PMID: 8332529

Ballhausen09: Ballhausen B, Altendorf K, Deckers-Hebestreit G (2009). "Constant c10 ring stoichiometry in the Escherichia coli ATP synthase analyzed by cross-linking." J Bacteriol 191(7);2400-4. PMID: 19181809

Barzu83: Barzu O, Michelson S (1983). "Simple and fast purification of Escherichia coli adenylate kinase." FEBS Lett 1983;153(2);280-4. PMID: 6311616

Bass87: Bass MB, Fromm HJ, Stayton MM (1987). "Overproduction, purification, and characterization of adenylosuccinate synthetase from Escherichia coli." Arch Biochem Biophys 1987;256(1);335-42. PMID: 3038024

BekeSomfai11: Beke-Somfai T, Lincoln P, Norden B (2011). "Double-lock ratchet mechanism revealing the role of alphaSER-344 in FoF1 ATP synthase." Proc Natl Acad Sci U S A 108(12);4828-33. PMID: 21383131

Bennett04: Bennett SE, Chen CY, Mosbaugh DW (2004). "Escherichia coli nucleoside diphosphate kinase does not act as a uracil-processing DNA repair nuclease." Proc Natl Acad Sci U S A 101(17);6391-6. PMID: 15096615

Berardi99: Berardi MJ, Bushweller JH (1999). "Binding specificity and mechanistic insight into glutaredoxin-catalyzed protein disulfide reduction." J Mol Biol 292(1);151-61. PMID: 10493864

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Please cite the following article in publications resulting from the use of EcoCyc: Nucleic Acids Research 41:D605-12 2013
Page generated by Pathway Tools version 19.5 (software by SRI International) on Sat Apr 30, 2016, biocyc13.