Disease relevance of ADE4

• Yeast amidophosphoribosyltransferase is homologous to the enzymes from Escherichia coli and Bacillus subtilis [1].

High impact information on ADE4

• Consistently, both ADE4 dominant mutations and overexpression of wild-type ADE4 lead to deregulation of ADE gene expression [2].
• Importantly, feedback inhibition by ATP of Ade4p, catalyzing the first step of the pathway, appears to regulate SAICAR synthesis in response to adenine availability [2].
• Two GCREs are essential to synergistically activate ADE4 transcription by binding GCN4 [3].
• The nucleotide sequence of ADE4 along with upstream and downstream flanking sequences was determined [1].
• The ADE4 structural gene consists of 1530 base pairs from which a 510-amino acid translation product, Mr = 56,691, was deduced [1].

Chemical compound and disease context of ADE4

• Thus in the group, S. cerevisiae, E. coli, B. subtilis, the content of a [4Fe-4S] cluster in amidophosphoribosyltransferase correlates with a mechanism for oxygen-dependent inactivation of the enzyme [1].

Biological context of ADE4

• Transcriptional activation of yeast nucleotide biosynthetic gene ADE4 by GCN4 [3].
• The gene is located on chromosome XIII, downstream of the ADH2 gene and 10 cM from the ADE4 gene [4].
• We have stimulated mitotic and meiotic gene conversion between non-tandem direct repeats of ADE4 by a defined double-strand break imparted in vivo to one of two copies of the gene [5].
• Mutants at the ade4 locus of yeast were isolated following mutagenesis of ade+ and ade2 with ultraviolet light (UV), ethylmethane sulphonate, and the acridine half mustard ICR-170 [6].

Associations of ADE4 with chemical compounds

• They did not excrete purine when combined with ade4+ [7].
• Mutants of Saccharomyces cerevisiae deficient in adenine phosphoribosyltransferase (A-PRT, EC 2,4,2,7) have been isolated following selection for resistance to 8-azaadenine in a prototrophic strain carrying the ade4-su allele of the gene coding for amidophosphoribosyltransferase (EC 2,4,2,14) [7].
• Glutamine nucleotide sequence of Saccharomyces cerevisiae ADE4 encoding phosphoribosylpyrophosphate amidotransferase [1].
• Yeast amidophosphoribosyltransferase does not contain the previously deduced sequence required for binding of a [4Fe-4S] center indicating that a [4Fe-4S] center is an unlikely component of the yeast enzyme [1].
• Ade4-su, a prototrophic allele of ade4 with reduced activity of PRPPAT, is epistatic to hpt1, suppressing purine excretion and resistance to azaadenine but not resistance to azaguanine [8].

Other interactions of ADE4

• Furthermore, the transcription of ADE4 and SHM2 in the Deltabas1 mutant did not diminish during the transition from the trophic to the productive phase did not diminish, in contrast to what occurred in the wild-type strain [9].

Analytical, diagnostic and therapeutic context of ADE4

• Northern blots demonstrate that ADE4 expression is transcriptionally regulated [1].
• Real-time quantitative PCR analyses comparing the wild type and the Deltabas1 mutant revealed that AgBAS1 was responsible for the adenine-mediated regulation of the purine and glycine pathways, since the transcription of the ADE4 and SHM2 genes was virtually abolished in the Deltabas1 mutant [9].
• Molecular cloning of rat amidophosphoribosyltransferase [10].

References