If an enzyme name is shown in bold, there is experimental evidence for this enzymatic activity.
Locations of Mapped Genes:
|Superclasses:||Biosynthesis → Nucleosides and Nucleotides Biosynthesis → Purine Nucleotide Biosynthesis → Purine Nucleotides De Novo Biosynthesis|
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]
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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
Artin et al., 2009: 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
Assarsson et al., 2001: 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
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
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
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Berardi & Bushweller, 1999: 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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