Disease relevance of ARO7

• The overall structure is completely different from the reported structure of chorismate mutase from Bacillus subtilis [1].
• Comparison of the x-ray structures of allosteric chorismate mutase from the yeast Saccharomyces cerevisiae with Escherichia coli chorismate mutase/prephenate dehydratase suggested conserved active sites between both enzymes [2].

High impact information on ARO7

• Allosteric regulation of catalytic activity: Escherichia coli aspartate transcarbamoylase versus yeast chorismate mutase [3].
• The yeast chorismate mutase is regulated by tyrosine as feedback inhibitor and tryptophan as crosspathway activator [4].
• Refined molecular hinge between allosteric and catalytic domain determines allosteric regulation and stability of fungal chorismate mutase [4].
• Substrate conformational transitions in the active site of chorismate mutase: their role in the catalytic mechanism [5].
• Chorismate mutase acts at the first branch-point of aromatic amino acid biosynthesis and catalyzes the conversion of chorismate to prephenate [5].

Chemical compound and disease context of ARO7

• CONCLUSIONS: The endo-oxabicyclic inhibitor binds to yeast CM in a similar way as it does to the distantly related CM from E. coli [6].
• The Fourier transform infrared (FTIR) spectrum of the complex between prephenate and the monofunctional chorismate mutase from Bacillus subtilis displays one prominent band at 1714 cm-1 [7].

Biological context of ARO7

• The binding sites have been analyzed in the active enzyme by site directed mutagenesis of critical codons of the coding gene, ARO7 [8].
• The gene we termed YMC1 (yeast mitochondrial carrier) is located on chromosome XVI, closely downstream of ARO7 encoding chorismate mutase [9].
• Therefore, the evolution of the sophisticated allosteric regulation of yeast chorismate mutase requires as prerequisite (i) that the encoding ARO7 gene is not transcriptionally regulated, whereas (ii) the transcription of the competing feedback-regulated anthranilate synthase-encoding gene is controlled by availability of amino acids [10].
• The Nal-sensitive aro7 mutant cells were used to show that the resumption of Nal-inhibited nuclear activity and cell proliferation takes place while cytoplasmic Nal persists at concentrations inhibitory for the mutant chorismate mutase [11].
• The recessive allele of the HGS1 locus, hgs1-1, and the codominant allele of the HGS2 locus, HGS2-1, were necessary for the sensitive phenotypes, and alleles in the MSM1 locus, MSM1-1 and msm1-2, were responsible for the different sensitivity levels [12].

Anatomical context of ARO7

• As yeast-derived 1F7(Fab) catalyzes the chorismate mutase reaction with the same specific activity as antibody isolated from the hybridoma, our expression system now makes possible the application of classical and "reverse" genetics to the study and improvement of this first-generation abzyme [13].

Associations of ARO7 with chemical compounds

• Expression of an allosterically unregulated, constitutively activated chorismate mutase encoded by the ARO7(T226I) (ARO7(c)) allele depleted the chorismate pool [10].
• The crystal structure of the tyrosine-bound T state of allosteric yeast Saccharomyces cerevisiae chorismate mutase was solved by molecular replacement at a resolution of 2.8 angstroms using a monomer of the R-state structure as the search model [14].
• Yeast chorismate mutase (EC 5.4.99.5) shows homotropic activation by the substrate, allosteric activation by tryptophan, and allosteric inhibition by tyrosine [15].
• A glutamate residue in the catalytic center of the yeast chorismate mutase restricts enzyme activity to acidic conditions [2].
• Replacement of Glu-246 in the yeast chorismate mutase by glutamine changes the pH optimum for activity of the enzyme from a narrow to a broad pH range [2].

Other interactions of ARO7

• Finally, ROX1 was mapped to yeast chromosome XVI, near the ARO7-OSM2 locus [16].
• A GCN4 protein recognition element is not sufficient for GCN4-dependent regulation of transcription in the ARO7 promoter of Saccharomyces cerevisiae [17].
• Genetic analyses of the parents and the progeny indicated that the levels of inorganic mercury sensitivity were determined by three distinct loci, HGS1, HGS2 and MSM1 [12].

Analytical, diagnostic and therapeutic context of ARO7

• Immunological data, homology modeling, as well as electron microscopy studies, indicate that this chorismate mutase has a dimeric structure like the S. cerevisiae enzyme [18].
• The crystallization and preliminary X-ray analysis of allosteric chorismate mutase [19].
• Cloning and expression in yeast of a higher plant chorismate mutase. Molecular cloning, sequencing of the cDNA and characterization of the Arabidopsis thaliana enzyme expressed in yeast [20].
• Monofunctional chorismate mutase from Bacillus subtilis: FTIR studies and the mechanism of action of the enzyme [7].

References