GUD1 (YDL238c) encodes Saccharomyces cerevisiae guanine deaminase, an enzyme expressed during post‐diauxic growth

Saint-Marc, Christelle; Daignan‐Fornier, Bertrand

doi:10.1002/yea.1186

Cited by 15 publications

(15 citation statements)

References 15 publications

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“…Phosphate is an abundant molecule that is incorporated into ATP and transferred from ATP to a large number of small -Marc and Daignan-Fornier (2004) biomolecules including nucleotides, sugars, and lipids, but also macromolecules such as proteins. In yeast, the total phosphate concentration is in the hundred-millimolar range.…”

Section: Identification Of Phosphate-responsive Genesmentioning

confidence: 99%

Regulation of Amino Acid, Nucleotide, and Phosphate Metabolism in Saccharomyces cerevisiae

2012

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Ever since the beginning of biochemical analysis, yeast has been a pioneering model for studying the regulation of eukaryotic metabolism. During the last three decades, the combination of powerful yeast genetics and genome-wide approaches has led to a more integrated view of metabolic regulation. Multiple layers of regulation, from suprapathway control to individual gene responses, have been discovered. Constitutive and dedicated systems that are critical in sensing of the intra- and extracellular environment have been identified, and there is a growing awareness of their involvement in the highly regulated intracellular compartmentalization of proteins and metabolites. This review focuses on recent developments in the field of amino acid, nucleotide, and phosphate metabolism and provides illustrative examples of how yeast cells combine a variety of mechanisms to achieve coordinated regulation of multiple metabolic pathways. Importantly, common schemes have emerged, which reveal mechanisms conserved among various pathways, such as those involved in metabolite sensing and transcriptional regulation by noncoding RNAs or by metabolic intermediates. Thanks to the remarkable sophistication offered by the yeast experimental system, a picture of the intimate connections between the metabolomic and the transcriptome is becoming clear.

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Section: Identification Of Phosphate-responsive Genesmentioning

confidence: 99%

Regulation of Amino Acid, Nucleotide, and Phosphate Metabolism in Saccharomyces cerevisiae

2012

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“…GDA is a metalloenzyme that catalyzes the first step in purine catabolism by converting guanine to xanthine by hydrolytic deamination. GDA also regulates the total cellular purine-derived nucleotide pool by converting adenylic derivatives to guanine [1-2]. Since GDA activity is involved in guanine metabolism, this enzyme is essential for the regulation of intracellular levels of guanylic derivatives [2].…”

Section: Introductionmentioning

confidence: 99%

“…GDA also regulates the total cellular purine-derived nucleotide pool by converting adenylic derivatives to guanine [1-2]. Since GDA activity is involved in guanine metabolism, this enzyme is essential for the regulation of intracellular levels of guanylic derivatives [2]. Furthermore, in higher eukaryotes, GDA (also known as cypin) plays an important role in the development of neuronal morphology [3-5].…”

Section: Introductionmentioning

confidence: 99%

Identification of small molecule compounds with higher binding affinity to guanine deaminase (cypin) than guanine

Fernández

Sweet

Welsh³

et al. 2010

Bioorganic & Medicinal Chemistry

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Guanine deaminase (GDA; cypin) is an important metalloenzyme that processes the first step in purine catabolism, converting guanine to xanthine by hydrolytic deamination. In higher eukaryotes, GDA also plays an important role in the development of neuronal morphology by regulating dendritic arborization. In addition to its role in the maturing brain, GDA is thought to be involved in proper liver function since increased levels of GDA activity have been correlated with liver disease and transplant rejection. Although mammalian GDA is an attractive and potential drug target for treatment of both liver diseases and cognitive disorders, prospective novel inhibitors and/or activators of this enzyme have not been actively pursued. In this study, we employed the combination of protein structure analysis and experimental kinetic studies to seek novel potential ligands for human guanine deaminase. Using virtual screening and biochemical analysis, we identified common small molecule compounds that demonstrate a higher binding affinity to GDA than does guanine. In vitro analysis demonstrates that these compounds inhibit guanine deamination, and more surprisingly, affect GDA (cypin)-mediated microtubule assembly. The results in this study provide evidence that an in silico drug discovery strategy coupled with in vitro validation assays can be successfully implemented to discover compounds that may possess therapeutic value for the treatment of diseases and disorders where GDA activity is abnormal.

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“…Guanine deaminase, a critical enzyme in purine salvage, was elevated both at transcriptional (GUD1) (12.86-fold) and translational (1.78-fold) levels. This enzyme catalyzes the hydrolytic deamination of guanine, producing xanthine and ammonia [89]. Up transcripted 3',5'-cyclic-nucleotide phosphodiesterase (PDE1) catalyzes nucleoside 3',5'-cyclic phosphate to nucleoside 5'-phosphate [90], suggesting a decrease of the cAMP level.…”

Section: Cell Cycle and Multiplicationmentioning

confidence: 99%

Cuminal Inhibits Trichothecium roseum Growth by Triggering Cell Starvation: Transcriptome and Proteome Analysis

Zhang

et al. 2020

Microorganisms

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Trichothecium roseum is a harmful postharvest fungus causing serious damage, together with the secretion of insidious mycotoxins, on apples, melons, and other important fruits. Cuminal, a predominant component of Cuminum cyminum essential oil has proven to successfully inhibit the growth of T. roseum in vitro and in vivo. Electron microscopic observations revealed cuminal exposure impaired the fungal morphology and ultrastructure, particularly the plasmalemma. Transcriptome and proteome analysis was used to investigate the responses of T. roseum to exposure of cuminal. In total, 2825 differentially expressed transcripts (1516 up and 1309 down) and 225 differentially expressed proteins (90 up and 135 down) were determined. Overall, notable parts of these differentially expressed genes functionally belong to subcellular localities of the membrane system and cytosol, along with ribosomes, mitochondria and peroxisomes. According to the localization analysis and the biological annotation of these genes, carbohydrate and lipids metabolism, redox homeostasis, and asexual reproduction were among the most enriched gene ontology (GO) terms. Biological pathway enrichment analysis showed that lipids and amino acid degradation, ATP-binding cassette transporters, membrane reconstitution, mRNA surveillance pathway and peroxisome were elevated, whereas secondary metabolite biosynthesis, cell cycle, and glycolysis/gluconeogenesis were down regulated. Further integrated omics analysis showed that cuminal exposure first impaired the polarity of the cytoplasmic membrane and then triggered the reconstitution and dysfunction of fungal plasmalemma, resulting in handicapped nutrient procurement of the cells. Consequently, fungal cells showed starvation stress with limited carbohydrate metabolism, resulting a metabolic shift to catabolism of the cell's own components in response to the stress. Additionally, these predicaments brought about oxidative stress, which, in collaboration with the starvation, damaged certain critical organelles such as mitochondria. Such degeneration, accompanied by energy deficiency, suppressed the biosynthesis of essential proteins and inhibited fungal growth.fungicides to be used for postharvest treatment, reduced efficacy due to the emergence of pathogen resistance to these chemicals, and the growing public concerns over chemical residues in food and the environment have necessitated the seeking of alternative solutions to control the fungal spoilage and to guarantee food safety and consumer health [8].Essential oils (EOs), generally recognized as safe by the US Food and Drug Administration [9], are natural substances with established antimicrobial activities [10,11] and are a candidate instrument for controlling postharvest disease [12,13]. Nonetheless, this candidacy is compromised by the expensiveness of these natural substances due to their generally low yields. However, exploring their mode of actions is valuable to the development of novel alternatives.The multicomponent EOs attribute their mode of act...

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GUD1 (YDL238c) encodes Saccharomyces cerevisiae guanine deaminase, an enzyme expressed during post‐diauxic growth

Cited by 15 publications

References 15 publications

Regulation of Amino Acid, Nucleotide, and Phosphate Metabolism in Saccharomyces cerevisiae

Regulation of Amino Acid, Nucleotide, and Phosphate Metabolism in Saccharomyces cerevisiae

Identification of small molecule compounds with higher binding affinity to guanine deaminase (cypin) than guanine

Cuminal Inhibits Trichothecium roseum Growth by Triggering Cell Starvation: Transcriptome and Proteome Analysis

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