Disease relevance of ARO4

• Without aromatic amino acids, this yeast strain survives only when the yeast ARO3 promoter instead of the ARO4 promoter drives E. coli aroH [1].
• The ARO4 terminator and the HIS7 promoter regions are sensitive to Micrococcus nuclease (Mnase) and separated by a positioned nucleosome [2].
• Crystal structure of the reaction complex of 3-deoxy-D-arabino-heptulosonate-7-phosphate synthase from Thermotoga maritima refines the catalytic mechanism and indicates a new mechanism of allosteric regulation [3].

High impact information on ARO4

• The ARO3-encoded 3-deoxy-D-arabino-heptulosonate-7-phosphate synthase (EC 4.1.2.15) is feedback inhibited by phenylalanine; its isoenzyme, the ARO4 gene product, is inhibited by tyrosine [4].
• Multiple factors prevent transcriptional interference at the yeast ARO4-HIS7 locus [5].
• Deletion analyses of the region between the two open reading frames revealed that transcriptional interference increases upon removal of either parts of the ARO4 3' end or HIS7 promoter sequences [5].
• Nitrogen starvation increases GCN4 transcription but efficiently represses expression of both a synthetic GCRE6::lacZ reporter gene and the natural amino acid biosynthetic gene ARO4 [6].
• Replacement of the housekeeping ARO4 promoter by the stronger ACT1 promoter leads to reduced HIS7 expression due to transcriptional interference [7].

Biological context of ARO4

• ARO4 gene expression is regulated by the general control system of aa biosynthesis [8].
• Activity of the tyrosine-inhibitable 3-deoxy-d-arabino-heptulosonate-7-phosphate synthase (EC 4.1.2.15) from Saccharomyces cerevisiae that was encoded by the ARO4 gene cloned on a high-copy-number plasmid was enhanced 64-fold as compared to the wild-type [9].
• 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 [10].
• The ARO4 gene of Candida albicans encodes a tyrosine-sensitive DAHP synthase: evolution, functional conservation and phenotype of Aro3p-, Aro4p-deficient mutants [10].
• The open reading frames of ARO4 and HIS7 are tandemly transcribed and are separated by 416 bp [5].

Associations of ARO4 with chemical compounds

• Here, we report the cloning and characterization of the ARO4 gene, encoding the second DAHPS, which is inhibited by tyrosine [8].
• In Saccharomyces cerevisiae, the genes ARO3 and ARO4 encode isoenzymes of 3-deoxy-D-arabino-heptulosonate-7-phosphate (DAHP) synthase [11].
• 3-Deoxy-d-arabino-heptulosonate-7-phosphate synthase (DAHPS) catalyzes the first reaction of the aromatic biosynthetic pathway in bacteria, fungi, and plants, the condensation of phosphoenolpyruvate (PEP) and d-erythrose-4-phosphate (E4P) with the formation of DAHP [3].

Other interactions of ARO4

• However, in contrast to the situation in the isogene, ARO3, GCN4 does not contribute to the basal level of ARO4 transcription under nonderepressing conditions [8].
• Exchanging the TRP4 3'UTR by the bidirectional ARO4 or the unidirectional GCN4 3' end formation element allowed efficient gene expression [12].

Analytical, diagnostic and therapeutic context of ARO4

• 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 [13].
• Crystallization and preliminary X-ray analysis of 3-deoxy-D-arabino-heptulosonate-7-phosphate synthase (tyrosine inhibitable) from Saccharomyces cerevisiae [14].

References