Allosteric Regulation of Catalytic Activity:
            <i>Escherichia coli</i>
            Aspartate Transcarbamoylase versus Yeast Chorismate Mutase

Helmstaedt, Kerstin; Krappmann, Sven; Braus, Gerhard H.

doi:10.1128/mmbr.65.3.404-421.2001

Cited by 68 publications

(49 citation statements)

References 112 publications

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“…Gene duplication and the transcriptional regulation of the general control network of amino acid biosynthesis finally resulted in two Gcn4p-regulated genes encoding for highly effective and closely related DAHPS activities, with additional regulation by Tyr and Phe, DAHPS Tyr (Aro4p) and DAHPS Phe (Aro3p), respectively. Tryptophan regulation in yeast was shifted downstream in the pathway to the first branch point because chorismate mutase evolved as an important key regulator that was activated by Trp and inhibited by Tyr (50). At this strongly regulated branch point, anthranilate synthase encoded by TRP2 and TRP3, which is transcriptionally regulated by the general control (41), competes with chorismate mutase for chorismate.…”

Section: Discussionmentioning

confidence: 99%

Evolution of 3-deoxy- d - arabino -heptulosonate-7-phosphate synthase-encoding genes in the yeast Saccharomyces cerevisiae

Helmstaedt

Strittmatter

Lipscomb

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

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The shikimate pathway resulting in three aromatic amino acids is initiated in different organisms by two and three 3-deoxy-D-arabino-heptulosonate-7-phosphate synthases, respectively. Aro3p and Aro4p are the yeast enzymes feedback-inhibited by phenylalanine and tyrosine, respectively. A yeast strain deficient in the general control transcriptional regulatory system of amino acid biosynthesis is unable to live in the presence of high amounts of phenylalanine and tyrosine. Here, we show that this yeast strain can be rescued by the expression of aroH from Escherichia coli encoding the tryptophan-regulated AroH as third isoenzyme. Yeast carrying Ec AroH as the only enzyme for the initial step of the shikimate pathway can grow in the absence of tryptophan. Without aromatic amino acids, this yeast strain survives only when the yeast ARO3 promoter instead of the ARO4 promoter drives E. coli aroH. The detailed analysis of Aro3p and Aro4p revealed a triple feedback control by tyrosine͞phenylalanine and tryptophan. Dissecting this control allowed engineering of Aro4p S195A as an enzyme, which is inhibited like AroH only by tryptophan. In addition, Aro4p variants were constructed that show an equally strong inhibition by tyrosine and tryptophan (Aro4p P165G Q302R) and in which the regulation by tyrosine and tryptophan was reversed (Aro4p P165G). Our data suggest that yeast possesses only two instead of three isogenes encoding 3-deoxy-D-arabinoheptulosonate-7-phosphate synthases because both isoenzymes can be fine tuned by tryptophan as additional effector and because transcriptional regulation by the general control system can be induced as backup when aromatic amino acids in the environment are imbalanced.general control ͉ Aro4p ͉ AroH

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Section: Discussionmentioning

confidence: 99%

Evolution of 3-deoxy- d - arabino -heptulosonate-7-phosphate synthase-encoding genes in the yeast Saccharomyces cerevisiae

Helmstaedt

Strittmatter

Lipscomb

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

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“…CMs have been extensively studied, both functionally and structurally (Helmstaedt et al, 2001;Woycechowsky and Hilvert, 2004). Several high resolution structures of CM have been recently reported, including CM structures from Escherichia coli (Lee and Saier, 1983), Bacillus subtilis (Chook et al, 1994), Saccharomyces cerevisiae (Strater et al, 1996;Strater et al, 1997;Xue et al, 1994), Thermus thermophilus (Helmstaedt et al, 2004) and Mycobacterium tuberculosis (Qamra et al, 2006).…”

Section: Introductionmentioning

confidence: 99%

Structures of open (R) and close (T) states of prephenate dehydratase (PDT)—Implication of allosteric regulation by l-phenylalanine

Tan

Zhang

et al. 2008

Journal of Structural Biology

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The enzyme prephenate dehydratase (PDT) converts prephenate to phenylpyruvate in Lphenylalanine biosynthesis. PDT is allosterically regulated by L-Phe and other amino acids. We report the first crystal structures of PDT from Staphylococcus aureus in a relaxed (R) state and PDT from Chlorobium tepidum in a tense (T) state. The two enzymes show low sequence identity (27.3%) but the same prototypic architecture and domain organization. Both enzymes are tetramers (dimer of dimers) in crystal and solution while a PDT dimer can be regarded as a basic catalytic unit. The N-terminal PDT domain consists of two similar subdomains with a cleft in between, which hosts the highly conserved active site. In one PDT dimer two clefts are aligned to form an extended active site across the dimer interface. Similarly at the interface two ACT regulatory domains create two highly conserved pockets. Upon binding of the L-Phe inside the pockets, PDT transits from an open to a closed conformation.

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“…C horismate mutases (CMs) catalyze the Claisen rearrangement from chorismate to prephenate in the biosynthesis of tyrosine and phenylalanine (1). The eukaryotic CMs from Saccharomyces cerevisiae, Aspergillus nidulans, and Hansenula polymorpha exhibit a very similar pattern of regulation of enzyme activity (2).…”

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confidence: 99%

Refined molecular hinge between allosteric and catalytic domain determines allosteric regulation and stability of fungal chorismate mutase

Helmstaedt

Heinrich

Lipscomb

et al. 2002

Proc. Natl. Acad. Sci. U.S.A.

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The yeast chorismate mutase is regulated by tyrosine as feedback inhibitor and tryptophan as crosspathway activator. The monomer consists of a catalytic and a regulatory domain covalently linked by the loop L220s (212-226), which functions as a molecular hinge. Two monomers form the active dimeric enzyme stabilized by hydrophobic interactions in the vicinity of loop L220s. The role of loop L220s and its environment for enzyme regulation, dimerization, and stability was analyzed. Substitution of yeast loop L220s in place of the homologous loop from the corresponding and similarly regulated Aspergillus enzyme (and the reverse substitution) changed tyrosine inhibition to activation. Yeast loop L220s substituted into the Aspergillus enzyme resulted in a tryptophaninhibitable enzyme. Monomeric yeast chorismate mutases could be generated by substituting two hydrophobic residues in and near the hinge region. The resulting Thr-2123 Asp-Phe-283 Asp enzyme was as stable as wild type, but lost allosteric regulation and showed reduced catalytic activity. These results underline the crucial role of this molecular hinge for inhibition, activation, quaternary structure, and stability of yeast chorismate mutase.

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Allosteric Regulation of Catalytic Activity: Escherichia coli Aspartate Transcarbamoylase versus Yeast Chorismate Mutase

Cited by 68 publications

References 112 publications

Evolution of 3-deoxy- d - arabino -heptulosonate-7-phosphate synthase-encoding genes in the yeast Saccharomyces cerevisiae

Evolution of 3-deoxy- d - arabino -heptulosonate-7-phosphate synthase-encoding genes in the yeast Saccharomyces cerevisiae

Structures of open (R) and close (T) states of prephenate dehydratase (PDT)—Implication of allosteric regulation by l-phenylalanine

Refined molecular hinge between allosteric and catalytic domain determines allosteric regulation and stability of fungal chorismate mutase

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