Chorismate enzymatic

Chorismate Mutase catalyzed Claisen Rearrangement- 10 rate enhancement over non-enzymatic reaction... 

The differences in the rate constant for the water reaction and the catalyzed reactions reside in the mole fraction of substrate present as near attack conformers (NACs).171 These results and knowledge of the importance of transition-state stabilization in other cases support a proposal that enzymes utilize both NAC and transition-state stabilization in the mix required for the most efficient catalysis. Using a combined QM/MM Monte Carlo/free-energy perturbation (MC/FEP) method, 82%, 57%, and 1% of chorismate conformers were found to be NAC structures (NACs) in water, methanol, and the gas phase, respectively.172 The fact that the reaction occurred faster in water than in methanol was attributed to greater stabilization of the TS in water by specific interactions with first-shell solvent molecules. The Claisen rearrangements of chorismate in water and at the active site of E. coli chorismate mutase have been compared.173 It follows that the efficiency of formation of NAC (7.8 kcal/mol) at the active site provides approximately 90% of the kinetic advantage of the enzymatic reaction as compared with the water reaction. 

Aryl side chain containing L-a-amino acids, such as phenylalanine (Phe), tyrosine (Tyr), and tryptophan (Trp), are derived through the shikimate pathway. The enzymatic transformation of phosphoenolpyr-uvate (PEP) and erythro-4-phosphate, through a series of reactions, yields shikimate (Scheme 2). Although shikimate is an important biosynthetic intermediate for a number of secondary metabolites, this chapter only describes the conversion of shikimate to amino acids containing aryl side chains. In the second part of the biosynthesis, shikimate is converted into chorismate by the addition of PEP to the hydroxyl group at the C5 position. Chorismate is then transformed into prephenate by the enzyme chorismate mutase (Scheme 3). 

Chemical properties appropriate to a compound found at a branch point of metabolism are displayed by chorismic acid. Simply warming the compound in acidic aqueous solution yields a mixture of prephen-ate and para-hydroxybenzoate (corresponding to reactions h and l of Fig. 25-1). Note that the latter reaction is a simple elimination of the enolate anion of pyruvate. As indicated in Fig. 25-1, these reactions correspond to only two of several metabolic reactions of the chorismate ion. In E. coli the formation of phe-nylpyruvate (steps h and i, Fig. 25-1) is catalyzed by a single protein molecule with two distinctly different enzymatic activities chorismate mutase and prephenate dehydratase.34-36 However, in some organisms the enzymes are separate.37 Both of the reactions catalyzed by these enzymes also occur spontaneously upon warming chorismic acid in acidic solution. The chorismate mutase reaction, which is unique in its mechanism,373 is discussed in Box 9-E. Stereochemical studies indicate that the formation of phenylpyruvate in Fig. 25-1, step z, occurs via a... 

Using the transition-state analog shown on p. 485 a catalytic antibody with chorismate mutase activity was isolated. Many antibodies catalyzing additional reactions have also been found. Although they are usually less active than natural enzymes, in some cases they approach enzymatic rates. Furthermore, they may catalyze reactions for which no known enzymes exist.h... 

Marti S, J Andres, V Moliner, E Silla, I Tunon, J Bertran (2000) A QM/MM study of the conformational equilibria in die chorismate mutase active site. The role of the enzymatic deformation energy contribution. J. Phys. Chem. B 104 (47) 11308—11315... 

The bacterial enzyme chorismate mutase-prephenate dehydrogenase is peculiar because it is a single protein unit with two catalytic activities. It catalyzes the sequential reactions of mutation of chorismate to prephenate and then the reaction that leads to the formation of phenylalanine and tyrosine, through oxidation of prephenate. The first of these reactions is interesting because it is one of the few strictly single-substrate enzymatic reactions it entails... 

Microbes and plants synthesize aromatic compounds to meet their needs of aromatic amino acids (L-Phe, L-Tyr and L-Trp) and vitamins. The biosynthesis of these aromatics [69] starts with the aldol reaction of D-erythrose-4-phosphate (E4P) and phosphoenolpyruvate (PEP), which are both derived from glucose via the central metabolism, into DAHP (see Fig. 8.13). DAHP is subsequently converted, via a number of enzymatic steps, into shikimate (SA) and eventually into chorismate (CHA, see later), which is the common intermediate in the biosynthesis of the aromatic amino acids [70] and vitamins. 

The transition state for the enzymatic reaction has been shown to have a chairlike geometry as well [61], and conformationally constrained compounds that mimic this structure, such as the oxabicyclic dicarboxylic acid 1 (Fig. 3.6), are good inhibitors of chorismate mutase enzymes [62 - 64], How a protein might stabilize this high-energy species has been a matter of some debate. Recently, heavy atom isotope effects were used to characterize the structure of the transition state bound to BsCM [65]. A very... 

Kinetic characterization of several selected BsCM variants shows that truncation or mutation of the C-terminal tail has little effect on the turnover number (fcc ll) of the enzyme (Tab. 3.1). When chorismate is bound to the active site of the variants, it is converted to prephenate nearly as efficiently as with wild-type BsCM. However, a substantial reduction in the k /K value is evident (Tab. 3.1). This finding indicates that the C-terminus, while not directly involved in the chemical transformation of bound ligand, does contribute to enzymatic efficiency by uniform binding of substrate and transition state. 

Ishida, T. Effects of point mutation on enzymatic activity Correlation between protein electronic structure and motion in chorismate mutase reaction, J. Am. Chem. Soc. 2010, 752,7104-7118. 

Copely, S. D. Knowles, J. R., The Conformational Equilibrium of Chorismate in Solution Implications for the Mechanism of the Non-Enzymatic and the Enzyme-Catalyzed Rearrangement of Chorismate to PrephenatePJ.Am. Chem. Soc. 1987, 109,5008. 

The Claisen rearrangement, which displays a negative activation volume, is also accelerated in water. Thus, the non-enzymatic rearrangement of chorismate to pre-phenate occurs 100 times faster in water than in methanol [55]. The accelerating... 

Enzymatic studies with chorismate mutase prephenate dehydrogenase from Escherichia coli show that the chorismate prephenate analog 7 is not a substrate for chorismate mutase65. Both 7 and 8 are moderately competitive inhibitors for chorismate mutase. Ester derivatives 4 and 5, as well as 6, readily undergo Claisen rearrangements in organic solvents. 

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