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discounted EARLY registration ends Dec 31, 2014
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Metabolic Modeling Tutorial
discounted EARLY registration ends Dec 31, 2014
BioCyc websites down
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Metabolic Modeling Tutorial
discounted EARLY registration ends Dec 31, 2014
BioCyc websites down
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discounted EARLY registration ends Dec 31, 2014
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Escherichia coli K-12 substr. MG1655 Pathway: superpathway of guanosine 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:

Genetic Regulation Schematic: ?

Superclasses: Biosynthesis Nucleosides and Nucleotides Biosynthesis Purine Nucleotide Biosynthesis Purine Nucleotides De Novo Biosynthesis
Superpathways

Summary:
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 this pathway, or adenosine nucleotides as shown in pathway superpathway of guanosine nucleotides de novo biosynthesis II.

About This Pathway

The conversion of IMP to GMP is catalyzed by the consecutive action of IMP dehydrogenase and GMP synthetase encoded by guaB and guaA, respectively. The former enzyme is the first committed step in GMP synthesis. The latter enzyme catalyzes the replacement of an oxygen atom at the 2-position of XMP with an amino group, utilizing either L-glutamine or ammonia. The specific kinase product of gene gmk converts GMP to GDP. GMP can also be supplied by a salvage pathway as indicated by the pathway link. However, rapidly growing cells may require more GMP than can be supplied by the salvage pathway (reviewed in [Hedstrom09]).

Both GDP and GTP can be converted to the deoxy forms of the nucleotide. GTP is converted to dGTP by ribonucleoside-triphosphate reductase, while GDP can be converted to dGDP by either ribonucleoside diphosphate reductase 1 or ribonucleoside-diphosphate reductase 2. Finally, nucleoside diphosphate kinase can also convert dGDP to dGTP.

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: guanosine deoxyribonucleotides de novo biosynthesis II , guanosine ribonucleotides de novo biosynthesis

Variants: superpathway of adenosine nucleotides de novo biosynthesis II

Credits:
Created 13-Jan-2009 by Caspi R , SRI International
Last-Curated ? 05-Jan-2012 by Fulcher C , SRI International


References

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

Hedstrom09: Hedstrom L (2009). "IMP dehydrogenase: structure, mechanism, and inhibition." Chem Rev 109(7);2903-28. PMID: 19480389

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

Abbott06: Abbott JL, Newell JM, Lightcap CM, Olanich ME, Loughlin DT, Weller MA, Lam G, Pollack S, Patton WA (2006). "The Effects of Removing the GAT Domain from E. coli GMP Synthetase." Protein J 25;483-491. PMID: 17103135

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

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

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

Bairoch93a: Bairoch A, Boeckmann B (1993). "The SWISS-PROT protein sequence data bank, recent developments." Nucleic Acids Res. 21:3093-3096. PMID: 8332529

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

Bernard00: Bernard MA, Ray NB, Olcott MC, Hendricks SP, Mathews CK (2000). "Metabolic functions of microbial nucleoside diphosphate kinases." J Bioenerg Biomembr 32(3);259-67. PMID: 11768309

Boal10: Boal AK, Cotruvo JA, Stubbe J, Rosenzweig AC (2010). "Structural basis for activation of class Ib ribonucleotide reductase." Science 329(5998);1526-30. PMID: 20688982

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

Brignole12: Brignole EJ, Ando N, Zimanyi CM, Drennan CL (2012). "The prototypic class Ia ribonucleotide reductase from Escherichia coli: still surprising after all these years." Biochem Soc Trans 40(3);523-30. PMID: 22616862

Brown69: Brown NC, Canellakis ZN, Lundin B, Reichard P, Thelander L (1969). "Ribonucleoside diphosphate reductase. Purification of the two subunits, proteins B1 and B2." Eur J Biochem 1969;9(4);561-73. PMID: 4896737

Brown69a: Brown NC, Reichard P (1969). "Ribonucleoside diphosphate reductase. Formation of active and inactive complexes of proteins B1 and B2." J Mol Biol 46(1);25-38. PMID: 4902211

Butland05: Butland G, Peregrin-Alvarez JM, Li J, Yang W, Yang X, Canadien V, Starostine A, Richards D, Beattie B, Krogan N, Davey M, Parkinson J, Greenblatt J, Emili A (2005). "Interaction network containing conserved and essential protein complexes in Escherichia coli." Nature 433(7025);531-7. PMID: 15690043

Casado91: Casado C, Llagostera M, Barbe J (1991). "Expression of nrdA and nrdB genes of Escherichia coli is decreased under anaerobiosis." FEMS Microbiol Lett 1991;67(2);153-7. PMID: 1778429

Chittur01: Chittur SV, Klem TJ, Shafer CM, Davisson VJ (2001). "Mechanism for acivicin inactivation of triad glutamine amidotransferases." Biochemistry 40(4);876-87. PMID: 11170408

Cotruvo08: Cotruvo JA, Stubbe J (2008). "NrdI, a flavodoxin involved in maintenance of the diferric-tyrosyl radical cofactor in Escherichia coli class Ib ribonucleotide reductase." Proc Natl Acad Sci U S A 105(38):14383-8. PMID: 18799738

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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 SRI International Pathway Tools version 18.5 on Fri Dec 19, 2014, BIOCYC14A.