Disease relevance of ARO3

• Without aromatic amino acids, this yeast strain survives only when the yeast ARO3 promoter instead of the ARO4 promoter drives E. coli aroH [1].

High impact information on ARO3

• Aro3p and Aro4p are the yeast enzymes feedback-inhibited by phenylalanine and tyrosine, respectively [1].
• The detailed analysis of Aro3p and Aro4p revealed a triple feedback control by tyrosine/phenylalanine and tryptophan [1].
• Sequence alignments with phenylalanine-regulated DAHP synthases including Aro3p show a highly conserved serine residue at this position [2].
• The amount of GCN4 protein present in repressed wild-type cells therefore seems to contribute to a basal level of ARO3 gene expression [3].
• In addition, ARO3 gene expression cannot be elevated under amino acid starvation conditions [3].

Biological context of ARO3

• An ARO3 aro4 strain with gcn4 genetic background has the same phenotype of low ARO3 gene expression and slow growth [3].
• The complete functional ARO3 promoter comprises 231 base pairs and contains only one TGACTA binding site for the general control activator protein GCN4 [3].
• Phylogenetic analysis places the fungal DAHP synthases in a cluster separate from prokaryotic orthologues and suggests that ARO3 and ARO4 arose from a single gene via a gene duplication event early in fungal evolution [4].
• A combined deletion and mutation analysis of the ARO3 promoter region in a delta gcn4-background revealed two additional regulatory systems involved in ARO3 transcription [5].
• We took advantage of the high degree of aa sequence homology between DAHPSs from several species to isolate ARO3 homologues from the pathogenic yeast Candida albicans [6].

Associations of ARO3 with chemical compounds

• The ARO3 gene encodes one of two 3-deoxy-D-arabino-heptulosonate-7-phosphate isoenzymes in Saccharomyces cerevisiae catalyzing the first step in the biosynthesis of aromatic amino acids [3].
• Cells of Saccharomyces cerevisiae contain two catalytically redundant DAHP synthases, encoded by the genes ARO3 and ARO4, whose activities are feedback-inhibited by phenylalanine and tyrosine, respectively [4].
• The phenylalanine-inhibited DAHPS is encoded by the previously isolated and characterized ARO3 gene [7].
• This is in contrast to the ARO3-encoded isoenzyme, where phenylalanine is a competitive inhibitor with erythrose 4-phosphate as a substrate of the enzyme and a noncompetitive inhibitor with phosphoenolpyruvate as substrate [8].

Regulatory relationships of ARO3

• The ARO3 gene is (i) activated through a sequence element which binds the multifunctional DNA-binding protein ABF1 in vitro and (ii) repressed through an URS1 element, which binds the same protein in vitro as the URS1 element in the CAR1 promoter [5].

Other interactions of ARO3

• Both genes ARO3 and ARO4 are strongly regulated under the general control regulatory system [3].
• The general control activator protein GCN4 is essential for a basal level of ARO3 gene expression in Saccharomyces cerevisiae [3].
• Activation of the ARO3 gene through the ABF1-binding site and repression through the URS1 element seem to be independent of each other and independent of activation by the GCN4 protein [5].

Analytical, diagnostic and therapeutic context of ARO3

• An ARO3/ARO4-specific sequence was generated from C. albicans genomic DNA by polymerase chain reaction amplification and used as a probe to screen a C. albicans cDNA library [6].

References