If an enzyme name is shown in bold, there is experimental evidence for this enzymatic activity.
|Superclasses:||Biosynthesis → Nucleosides and Nucleotides Biosynthesis → Purine Nucleotide Biosynthesis → Purine Nucleotides De Novo Biosynthesis|
Expected Taxonomic Range: Bacteria
Purine nucleotides participate in many aspects of cellular metabolism including the structure of DNA and RNA, serving as enzyme cofactors, functioning in cellular signaling, acting as phosphate group donors, and generating cellular energy. Maintenance of the proper balance of intracellular pools of these nucleotides is critical to normal function. This occurs through a combination of de novo biosynthesis and salvage pathways for pre-existing purine bases, nucleosides and nucleotides.
The de novo biosynthetic pathway for purine nucleotides is highly conserved among organisms, but its regulation and the organization of the genes encoding the enzymes vary. This fourteen step pathway contains ten steps that branch at IMP to form AMP and GMP, each in two steps. Regulation of the pathway has been well studied in microbes such as Escherichia coli, Bacillus subtilis and Saccharomyces cerevisiae, but little is known about its regulation in higher eukaryotes (metazoa, and plants [Senecoff96]). The pathway appears to vary in archaea [White97]. Some organisms, such as the mycoplasmas, do not biosynthesize purine and pyrimidine bases de novo and must rely on salvage pathways [Wang01].
In bacterial systems genetic studies indicate that the majority of de novo purine biosynthetic genes are unlinked but may act as a single unit of regulation controlled by the PurR transcriptional repressor protein. In Escherichia coli the 14 reactions involved in the de novo synthesis of AMP and GMP are catalyzed by 12 known genes. These genes occur mostly as unlinked single units or as small functional operons carrying two or, at the most, three structural genes each. The purR gene encodes the repressor controlling the synthesis of all of these enzymes. Sequences similar to the protected region (PUR box) in purF are present in the regulatory regions of purMN. The expression of purR was shown to be autoregulated, probably through blocking of transcription elongation by binding of PurR to the two PUR boxes. So far, six genes/operons have been reported to contain PUR box-like sequences. The purine biosynthetic pathway is controlled by feedback regulation of activity as well as at the level of transcription [Meng90].
Reactions that convert ADP to ATP are found in multiple pathways, including fueling pathways such as anaerobic respiration, TCA-aerobic respiration, fermentation, and glycolysis, and are thus not included in this pathway.
Subpathways: guanosine ribonucleotides de novo biosynthesis , guanosine deoxyribonucleotides de novo biosynthesis II , superpathway of guanosine nucleotides de novo biosynthesis II , superpathway of adenosine nucleotides de novo biosynthesis II , inosine-5'-phosphate biosynthesis I , 5-aminoimidazole ribonucleotide biosynthesis II , adenosine deoxyribonucleotides de novo biosynthesis II , adenosine ribonucleotides de novo biosynthesis
Unification Links: EcoCyc:DENOVOPURINE2-PWY
Martha Arnaud on Tue Jan 21, 2003:
This pathway supersedes the pathway formerly called "purine biosynthesis."
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
Neidhardt96: Neidhardt FC, Curtiss III R, Ingraham JL, Lin ECC, Low Jr KB, Magasanik B, Reznikoff WS, Riley M, Schaechter M, Umbarger HE "Escherichia coli and Salmonella, Cellular and Molecular Biology, Second Edition." American Society for Microbiology, Washington, D.C., 1996.
Senecoff96: Senecoff JF, McKinney EC, Meagher RB (1996). "De novo purine synthesis in Arabidopsis thaliana. II. The PUR7 gene encoding 5'-phosphoribosyl-4-(N-succinocarboxamide)-5-aminoimidazole synthetase is expressed in rapidly dividing tissues." Plant Physiol 112(3);905-17. PMID: 8938402
Wang01: Wang L, Westberg J, Bolske G, Eriksson S (2001). "Novel deoxynucleoside-phosphorylating enzymes in mycoplasmas: evidence for efficient utilization of deoxynucleosides." Mol Microbiol 42(4);1065-73. PMID: 11737647
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
Aiba89: Aiba A, Mizobuchi K (1989). "Nucleotide sequence analysis of genes purH and purD involved in the de novo purine nucleotide biosynthesis of Escherichia coli." J Biol Chem 1989;264(35);21239-46. PMID: 2687276
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
Alenin92: Alenin VV, Ostanin KV, Kostikova TR, Domkin VD, Zubova VA, Smirnov MN (1992). "[Substrate specificity of phosphoribosyl-aminoimidazole-succinocarboxamide synthetase (SAICAR-synthetase) from Saccharomyces cerevisiae yeast]." Biokhimiia 1992;57(6);845-55. PMID: 1420588
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
Anand04: Anand R, Hoskins AA, Stubbe J, Ealick SE (2004). "Domain organization of Salmonella typhimurium formylglycinamide ribonucleotide amidotransferase revealed by X-ray crystallography." Biochemistry 43(32);10328-42. PMID: 15301531
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.
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
Axelrod08: Axelrod HL, McMullan D, Krishna SS, Miller MD, Elsliger MA, Abdubek P, Ambing E, Astakhova T, Carlton D, Chiu HJ, Clayton T, Duan L, Feuerhelm J, Grzechnik SK, Hale J, Han GW, Haugen J, Jaroszewski L, Jin KK, Klock HE, Knuth MW, Koesema E, Morse AT, Nigoghossian E, Okach L, Oommachen S, Paulsen J, Quijano K, Reyes R, Rife CL, van den Bedem H, Weekes D, White A, Wolf G, Xu Q, Hodgson KO, Wooley J, Deacon AM, Godzik A, Lesley SA, Wilson IA (2008). "Crystal structure of AICAR transformylase IMP cyclohydrolase (TM1249) from Thermotoga maritima at 1.88 A resolution." Proteins 71(2);1042-9. PMID: 18260100
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
Showing only 20 references. To show more, press the button "Show all references".
©2014 SRI International, 333 Ravenswood Avenue, Menlo Park, CA 94025-3493