If an enzyme name is shown in bold, there is experimental evidence for this enzymatic activity.
Locations of Mapped Genes:
Synonyms: deazapurine biosynthesis
|Superclasses:||Biosynthesis → Secondary Metabolites Biosynthesis|
7-Deazapurines are compounds that contain pyrrolopyrimidine functional groups (similar to purines, but lackinging one of the nitrogens in the pentameric ring). These compounds form a structurally diverse class of nucleoside analogues that often possess antibiotic, antineoplastic, or antiviral activities.
An important 7-deazapurine compound is queuosine, a modified nucleoside that is present in certain tRNAs in bacteria and most eukaryotes (with the exception of mycoplasmas and yeast), but not in the archaea [IwataReuyl03]. The pathway describing the biosynthesis of queuosine can be found at queuosine biosynthesis.
The biosynthesis of all 7-deazapurines proceeds via the common intermediate preQ0, which is produced in four steps from the nucleotide GTP. The pathway starts with the conversion of GTP to 7,8-dihydroneopterin 3'-triphosphate by GTP cyclohydrolase I, an enzyme that is also involved in the biosynthesis of tetrahydropteroyl mono-L-glutamate. 7,8-dihydroneopterin 3'-triphosphate is converted to 6-carboxy-5,6,7,8-tetrahydropterin by the action of 6-carboxy-5,6,7,8-tetrahydropterin synthase.
This intermediate is converted to 7-carboxy-7-deazaguanine by an unusual transformation catalyzed by 7-carboxy-7-deazaguanine synthase (queE), a member of the radical SAM enzyme superfamily. The corresponding E. coli enzyme has not yet been identified, but an ortholog, queE, exists.
Finally, the carboxylate moiety of 7-carboxy-7-deazaguanine is converted to a nitrile in an ATP-dependent reaction in which ammonia serves as the nitrogen source. The reaction is catalyzed by 7-cyano-7-deazaguanine synthase, generating the final product, preQ0 [McCarty09].
McCarty09: McCarty RM, Somogyi A, Lin G, Jacobsen NE, Bandarian V (2009). "The deazapurine biosynthetic pathway revealed: in vitro enzymatic synthesis of PreQ(0) from guanosine 5'-triphosphate in four steps." Biochemistry 48(18);3847-52. PMID: 19354300
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
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
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
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
Gaur05: Gaur R, Varshney U (2005). "Genetic analysis identifies a function for the queC (ybaX) gene product at an initial step in the queuosine biosynthetic pathway in Escherichia coli." J Bacteriol 187(20);6893-901. PMID: 16199558
Katzenmeier91: Katzenmeier G, Schmid C, Kellermann J, Lottspeich F, Bacher A (1991). "Biosynthesis of tetrahydrofolate. Sequence of GTP cyclohydrolase I from Escherichia coli." Biol Chem Hoppe Seyler 1991;372(11);991-7. PMID: 1665332
Marincs06: Marincs F, Manfield IW, Stead JA, McDowall KJ, Stockley PG (2006). "Transcript analysis reveals an extended regulon and the importance of protein-protein co-operativity for the Escherichia coli methionine repressor." Biochem J 396(2);227-34. PMID: 16515535
Meining95: Meining W, Bacher A, Bachmann L, Schmid C, Weinkauf S, Huber R, Nar H (1995). "Elucidation of crystal packing by X-ray diffraction and freeze-etching electron microscopy. Studies on GTP cyclohydrolase I of Escherichia coli." J Mol Biol 253(1);208-18. PMID: 7473713
Miles14: Miles ZD, Roberts SA, McCarty RM, Bandarian V (2014). "Biochemical and structural studies of 6-carboxy-5,6,7,8-tetrahydropterin synthase reveal the molecular basis of catalytic promiscuity within the tunnel-fold superfamily." J Biol Chem 289(34);23641-52. PMID: 24990950
Nar95a: Nar H, Huber R, Auerbach G, Fischer M, Hosl C, Ritz H, Bracher A, Meining W, Eberhardt S, Bacher A (1995). "Active site topology and reaction mechanism of GTP cyclohydrolase I." Proc Natl Acad Sci U S A 92(26);12120-5. PMID: 8618856
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