Enolase mandelate racemase

Enolases mandelate racemase (MR), muconate-lactonizing enzyme (MLE), N-acetylamino acid racemase (NAAR) Hasson, 1998 Palmer, 1999... 

P. C. Babbitt, J. A. Gerlt, G. A. Petsko, and D. Ringe, Evolution of an enzyme active site the structure of a new crystal form of muconate lactonizing enzyme compared with mandelate racemase and enolase, Proc. Natl. Acad. Sci. USA 1998,... 

The enolase superfamily story started with the serendipitous discovery that two enzymes catalyzing very different overall reactions, mandelate racemase (MR) and muconate lactonizing enzyme (MLE), had virtually superimposable structures (Neidhart et al., 1990). As shown in Figure 2, MR catalyzes the reversible racemization of mandelate, an aromatic substrate, while MLE catalyzes the equilibration of muconolactone with as, m-muconate. Given the substantial differences in these reactions, it... 

Both the 1,1-proton transfer reaction catalyzed by mandelate racemase (MR) and the dehydration catalyzed by enolase require Mg + for activity. The values of the pK s for mandelate and 2-phosphoglycerate, the substrates for the MR- and enolase-catalyzed reactions, are estimated as 29 and 32, respectively [1]. The values of the pKaS of the general basic Lys residues are 6 and 9 in MR [6] and enolase [73], respectively. Thus, formation of a dienolate anion intermediate is extremely endergonic, unless the active site can stabilize the intermediate which is the obvious function of the essential Mg. The rate accelerations for the MR- and enolase-catalyzed reactions are 10 as a direct result of the values of the pKaS of the a-protons (Table 6.1). 

The X-ray crystal structure of P. putida muconate lactonizing enzyme (cycloisomerase) was determined in 1987, and was found to contain an a/(i barrel fold, also found in triosephosphate isomerase and enolase. Remarkably, the structure of P. putida mandelate racemase, which catalyzes a mechanistically distinct reaction earlier in the same pathway, was found in 1990 to have a homologous structure, indicating that the structural fold of the enolase superfamily is able to support a range of enzyme-catalyzed reactions. The P. putida 3-carboxy- r, x-muconate lactonizing enzyme, in contrast, shares sequence similarity with a class II fumarase enzyme, and determination of its structure in 2004 has shown that it shares the same fold as the class II fumarase superfamily, hence these two catalysts of similar reactions have evolved from different ancestors. ... 

The First Members of the Enolase Superfamily to be Identified Mandelate Racemase and Muconate Lactonizing Enzyme... 

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