The Regulation of Activity of Phosphoribosylpyrophosphate Amidotransferase by Purine Ribonucleotides: A Potential Feedback Control of Purine Biosynthesis

Wyngaarden, James Β.; Ashton, Doris M.

doi:10.1016/s0021-9258(18)70036-7

Cited by 243 publications

(7 citation statements)

References 34 publications

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“…Alterations in the regulation of de novo purine biosynthesis could also bring 25 0 F. D. GILLIN et al about the observed changes in exogenous hypoxanthine utilization characteristic of our mutants. The first enzyme of de novo purine biosynthesis, glutamine: phosphoribosylpyrophosphate amidotransferase (EC 2.42.14) is inhibited by purines (WYNGAARDEN and ASHTON 1959;CASKEY, ASHTON and WYNGAARDEN 1964) and purine analogue ribonucleotides (MCCOLLISTER, GILBERT and ASHTON 1964), and is the site of feedback control for the de novo purine biosynthetic pathway. An 8-AG-resistant mutant of Schizosaccharomyces pombe ( NAGY 1970) which appears defective in amidotransferase feedback inhibition has now been identified.…”

Section: -Azaguanine Resistance 249mentioning

confidence: 99%

8-Azaguanine Resistance in Mammalian Cells I. Hypoxanthine-Guanine Phosphoribosyltransferase

et al. 1972

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Chinese hamster cells were treated with ethyl methanesulfonate or N-methyl-N'-nitro-N-nitrosoguanidine, and mutants resistant to 8-azaguanine were selected and characterized. Hypoxanthine-guanine phosphoribosyltransferase activity of sixteen mutants is extremely negative, making them suitable for reversion to HGPRTase+. Ten of the extremely negative mutants revert at a frequency higher than 10-7 suggesting their point mutational character. The remaining mutants have demonstrable HGPRTase activity and are not useful for reversion analysis. Five of these mutants have < 2% HGPRTase and are presumably also HGPRTase point mutants. The remaining 14 mutants utilize exogenous hypoxanthine for nucleic acid synthesis poorly, and possess 20-150% of wild-type HGPRTase activity in in vitro. Their mechanism of 8-azaguanine resistance is not yet defined.

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Section: -Azaguanine Resistance 249mentioning

confidence: 99%

8-Azaguanine Resistance in Mammalian Cells I. Hypoxanthine-Guanine Phosphoribosyltransferase

et al. 1972

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“…In the case of PRPP amidotransferase, K m of free ammonia is 400 times that of glutamine ( , ). Therefore, a high concentration of exogenous 15 NH 4 OAc is desired in order to increase the chance of intercepting any intermediate(s) formed during OST catalysis.…”

Section: Resultsmentioning

confidence: 99%

¹³C- and ¹⁵N-Labeled Peptide Substrates as Mechanistic Probes of Oligosaccharyltransferase

Coward

1997

Biochemistry

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The carboxamide moiety that links the carbohydrate and protein moieties in N-linked glycoproteins has been unambiguously determined to arise intact from asparagine by the use of chemically synthesized Bz-[4-13C, 15N]Asn-Leu-Thr-NH2 as an oligosaccharyltransferase (OST) substrate. Bz-[4-13C]Asn-Leu-Thr-NH2 was also synthesized and used to evaluate a proposed mechanism of OST catalysis similar to that of glutamine-dependent amidotransferases using 15NH4OAc as a potential external nucleophile. Analysis of NMR and MS spectra of the isotopically labeled peptides and the resulting biosynthesized glycopeptides indicates that free 15NH3 is not lost from the doubly labeled substrate during catalysis nor can exogenous 15NH3 intercept any of several postulated enzyme-bound species. These results indicate that OST-catalyzed glycosylation does not follow a mechanism involving the transient generation of exchangeable "NH3". Thus, in contrast to several glutamine-dependent amidotransferases, OST catalysis does not lead to transient scission of the asparagine beta-carboxamide C-N bond. Together with previously published results, these data argue against nucleophilic activation of the asparagine beta-carboxamide moiety being the underlying chemical mechanism for OST-catalyzed glycosylation of peptides.

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“…The PRPP amidotransferase activity in the dialyzed extracts was measured by the method of Wyngaarden and Ashton (1959) which depends on a coupled reaction with glutamate dehydrogenase and 3-acetylpyridine analogue of DPN for the spectometric estimation of glutamate produced by the amidotransferase. The assay system consisted of Tris-HC1 buffer, pH 8.0, 50 ~moles; MgCl~, 3 ~moles; PI~PP, Na salt, 0.25 ~mole; 1-glutamine, 1 ~mole; 3-acetylpyridine DPN, 0.6 ~mole; glutamie dehydrogenase, 0.05 ml of a four-fold dilution (freshly made in distilled water) of a purified, ammonium sulfate-free enzyme solution; I~eurospora extract, 0,05 ml in a final volume of 1.0 ml.…”

Section: A Phosphoribosylpyrophosphate Amidotransferase (Prpp Amidotransferase) Activity In the Revcrtantsmentioning

confidence: 99%

An unlinked mutation affecting control of purine metabolism in a revertant of an ad-7 auxotroph of Neurospora crassa lacking the phosphoribosylpyrophosphate amidotransferase

Jha

1972

Molec. Gen. Genetics

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Prototrophic revertants of an ad-7 mutant recover phosphoribosylpyrophosphate amidotransferase activity, indicating ad-7 is the structural gene for the first enzyme in the de novo biosynthesis of purine nucleotides. Some revertants excrete purines and cross-feed ad-3A conidia which have a lesion in the de novo pathway. A mutant apu, not linked to ad-7 or ad-8, is responsible for the ability to excrete purines. This mutation is not allelic to a mutant in the aza-1 locus which is also known to excrete purines.

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The Regulation of Activity of Phosphoribosylpyrophosphate Amidotransferase by Purine Ribonucleotides: A Potential Feedback Control of Purine Biosynthesis

Cited by 243 publications

References 34 publications

8-Azaguanine Resistance in Mammalian Cells I. Hypoxanthine-Guanine Phosphoribosyltransferase

8-Azaguanine Resistance in Mammalian Cells I. Hypoxanthine-Guanine Phosphoribosyltransferase

¹³C- and ¹⁵N-Labeled Peptide Substrates as Mechanistic Probes of Oligosaccharyltransferase

An unlinked mutation affecting control of purine metabolism in a revertant of an ad-7 auxotroph of Neurospora crassa lacking the phosphoribosylpyrophosphate amidotransferase

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The Regulation of Activity of Phosphoribosylpyrophosphate Amidotransferase by Purine Ribonucleotides: A Potential Feedback Control of Purine Biosynthesis

Cited by 243 publications

References 34 publications

8-Azaguanine Resistance in Mammalian Cells I. Hypoxanthine-Guanine Phosphoribosyltransferase

8-Azaguanine Resistance in Mammalian Cells I. Hypoxanthine-Guanine Phosphoribosyltransferase

13C- and 15N-Labeled Peptide Substrates as Mechanistic Probes of Oligosaccharyltransferase

An unlinked mutation affecting control of purine metabolism in a revertant of an ad-7 auxotroph of Neurospora crassa lacking the phosphoribosylpyrophosphate amidotransferase

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¹³C- and ¹⁵N-Labeled Peptide Substrates as Mechanistic Probes of Oligosaccharyltransferase