Mutase

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

T.-phenyl alanine C. glutamicum C. glutamicum aro F, chorismate mutase, PRDH 28 ... 

Adenosylcobalamin (coenzyme B 2) is required in a number of rearrangement reactions that occurring in humans is the methylmalonyl-Co A mutase-mediated conversion of (R)-methylmalonyl-Co A (6) to succinjl-CoA (7) (eq. 1). The mechanism of this reaction is poorly understood, although probably free radical in nature (29). The reaction is involved in the cataboHsm of valine and isoleucine. In bacterial systems, adenosylcobalamin drives many 1,2-migrations of the type exemplified by equation 1 (30). 

There is one exception to the rule that requires bulky hydrophobic residues to fill the interior of eight-stranded a/p barrels in order to form a tightly packed hydrophobic core. The coenzyme Biz-dependent enzyme methylmalonyl-coenzyme A mutase, the x-ray structure of which was determined by Phil Evans and colleagues at the MRC Laboratory of Molecular... 

Figure 4.4 Schematic diagram of the structure of the a/p-barrel domain of the enzyme methylmalonyl-coenzyme A mutase. Alpha helices are red, and p strands are blue. The inside of the barrel is lined by small hydrophilic side chains (serine and threonine) from the p strands, which creates a hole in the middle where one of the substrate molecules, coenzyme A (green), binds along the axis of the barrel from one end to the other. (Adapted from a computer-generated diagram provided by P. Evans.)...

The stmcture was determined to 2.8 A resolution in the laboratory of Tom Steitz, Yale University, (d) The glycolytic enzyme phospho-glycerate mutase, which catalyzes transfer of a phos-phoryl group from carbon 3 to carbon 2 In phosphoglycerate. The structure was determined to 2.S A resolution in the laboratory of Herman Watson, Bristol University, UK. (Adapted from J. Richardson.)... 

Campbell, J.W., Watson, H.C., Hodgson, G.I. Structure of yeast phosphoglycerate mutase. Nature 250 301-303, 1974. 

Mancia, E., et al. How coenzyme Biz radicals are generated the crystal structure of methylmalonyl-coen-zyme A mutase at 2 A resolution. Strueture 4 339-350, 1996. 

Mg-" Alcohol dehydrogenase Hexokinase 5 -Deoxyadenosylcobalamin (vitamin Big) H atoms and alkyl groups Me thy Im alony 1-CoA mutase... 

The remaining steps in the glycolytic pathway prepare for synthesis of the second ATP equivalent. This begins with the phosphoglycerate mutase reaction (Eigure 19.23), in which the phosphoryl group of 3-phosphoglycerate is moved... 

FIGURE 19.24 A mechanism for the phosphoglycerate mutase reaction in rabbit muscle and in yeast. Zelda Rose of the Institute for Cancer Research in Philadelphia showed that the enzyme requires a small amount of 2,3-BPG to phosphorylate the histidine residue before the mechanism can proceed. Prior to her work, the role of the phosphohistidine in this mechanism was not understood. 

FIGURE 19.25 The phosphoglycerate mutase of wheat germ catalyzes an intramolecn-lar phosphoryl transfer. 

D-Methylmalonyl-CoA, the product of this reaction, is converted to the L-isomer by methylmalonyl-CoA epunerase (Figure 24.19). (This enzyme has often and incorrectly been called methylmalonyl-CoA racemase. It is not a racemase because the CoA moiety contains five other asymmetric centers.) The epimerase reaction also appears to involve a carbanion at the a-position (Figure 24.20). The reaction is readily reversible and involves a reversible dissociation of the acidic a-proton. The L-isomer is the substrate for methylmalonyl-CoA mutase. Methylmalonyl-CoA epimerase is an impressive catalyst. The for the proton that must dissociate to initiate this reaction is approximately 21 If binding of a proton to the a-anion is diffusion-limited, with = 10 M sec then the initial proton dissociation must be rate-limiting, and the rate constant must be... 

Based on the mechanism for the methylmalonyl-CoA mutase (Eigure 24.21), write reasonable mechanisms for the reactions shown below. 

Methylmalonyl-CoA mutase 5 -deoxyadenosylco-balamin is part of dimethylbenzimidazolecobamide coenzyme, a constituent of methylmalonyl-CoA mutase. This mutase catalyses the isomerization of methylmalonyl-CoA to succinyl-CoA (anaplerotic reaction of the citric acid cycle). 

Methylmalonyl CoA mutase, leucine aminomutase, and methionine synthase (Figure 45-14) are vitamin Bj2-dependent enzymes. Methylmalonyl CoA is formed as an intermediate in the catabolism of valine and by the carboxylation of propionyl CoA arising in the catabolism of isoleucine, cholesterol, and, rarely, fatty acids with an odd number of carbon atoms—or directly from propionate, a major product of microbial fer-... 

Ratnatilleke A, JW Vrijbloed, JA Robinson (1999) Cloning and sequencing of the coenzyme B,2-binding domain of isobutyryl-CoA mutase from Streptomyces cinnamonensis. Reconstitution of mutase activity and characterization of the recombinant enzyme produced in Escherichia coli. J Biol Chem 274 31679-31685. 

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