A-Methyleneglutarate mutase

Chemaly, S. M., 1994, a-Methyleneglutarate mutase an adenosylcobalamin-dependent enzyme, S. Afr. J. Chem. 47 37947. 

MutQSes. Four enzymes are known that catalyze rearrangements of the carbon skeleton of the substrate molecules and which use adenosyl-cobamides (such as coenzyme B12 (2)) as their corrinoid cofactors (methylmalonyl-CoA mu-tase, glutamate mutase, a-methyleneglutarate mutase, and isobutyryl-CoA mu-tase see Table 1, entries 1-4) (10,62,63). Two adenosyl-cobamide-dependent enzymes catalyze the migration of an amino group in three substrate pairs... 

The structure of the E. coli enzyme (Fig. 16-24) shows methylcobalamin bound in a base-off conformation, with histidine 759 of the protein replacing dimethylbenzimidazole in the distal coordination position on the cobalt. This histidine is part of a sequence Asp-X-His-X-X-Gly that is found not only in methionine synthase but also in methylmalonyl-CoA mutase, glutamate mutase, and 2-methyleneglutarate mutase. However, diol dehydratase lacks this sequence and binds adenosylcobalamin with the dimethylbenz-imidazole-cobalt bond intact.417... 

FIGURE 21. Mechanisms for the rearrangement of substrate radicals in the reactions catalyzed by carbon skeleton mutases. For 2-methyleneglutarate mutase and the acyl-CoA mutases both associative (upper pathway) and dissociative (lower pathway) mechanisms have been proposed (Halpem, 1985 Bucket Golding, 1996), whereas for glutamate only a dissociative mechanism appears feasible. 

Scheme 5 Two pathways for 2-methyleneglutarate mutase (substrate 2-methyleneglutarate product (R)-3-methylitaconate). Path a Addition-elimination via substrate radical and product radical P with the participation of an intermediate radical I ...

We chose this reaction since it has been proposed as a model for the rearrangement of 2-methyleneglutarate to 3-methylitaconate, catalyzed by the coenzyme-B,2-dependent enzyme, 2-methyleneglutarate mutase [16, 26, 57]. More specifically, equation 2 represents the second step in the addition-elimination pathway (reaction c. Scheme 4) for a 1,2-shift. Additionally, this reaction has been widely studied experimentally [58] and has been described as the most precisely calibrated radical reaction [59]. 

The first is the fragmentation-recombination pathway (see mechanism a. Scheme 4), with acrylate and an acrylate-derived radical as the intermediate state (Scheme 6). This possibility has been suggested only recently, and is based on the reported inhibition of 2-methyleneglutarate mutase by acrylate [47], The second suggested mechanism is the addition-elimination pathway (see reaction c. Scheme 4), with a substituted cyclopropylcarbinyl radical as the intermediate (Scheme 6) [6, 26],... 

Once again a number of different pathways for the degenerate rearrangement of the aminopropyl radical can be considered (Scheme 9) [35], including pathways that are analogous to those examined as models for the reactions catalyzed by methyleneglutarate mutase (Scheme 7) and methylmalonyl-CoA mutase (Scheme 8). 

W. Buckel G. Broker H. Bothe A. J. Pierik B. T. Golding, Glutamate Mutase and 2-Methyleneglutarate Mutase. In Chemistry and Biochemistry ofB 2, R- Banerjee, Ed. Wiley-Interscience New York, 1999 pp 757-781. 

Methyleneglutarate mutase interconverts 2-methyleneglutarate and (if)-3-methyl-itaconate (Table 1, entry 3) in a radical reaction, induced by the 5 -deoxyadenosyl radical (from 2), and involves the rearrangement between a... 

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