Glutamate mutase coenzyme

Both methylmalonyl-CoA mutase and glutamate mutase share strikingly similar global folds (Figure 8), even though sequence similarity is limited to the small a/ 3 domain and their quaternary structures are quite different. The icatalytici domains of both enzymes take the form of a ( a/p)s TIM-barrel the Ca atoms of the two structures can be superimposed with an r.m.s. deviation of only 2 (Reitzer et al., 1999). However, the active site residues of these enzymes (other than those involved in binding the lower face of the coenzyme) do not seem to be conserved and the substrates are bound very differently. 

Bothe, H., Darley, D. J., Albracht, S. P., Gerfen, G. J., Golding, B. T., and Buckel, W., 1998, Identification of the 4-glutamyl radical as an intermediate in the carbon skeleton rearrangement catalyzed by coenzyme Bi2-dependent glutamate mutase from Clostridium cochlearium. Biochemistry 37 4105n4113. 

Chen, H. P., and Marsh, E. N. G., 1997, How enzymes control the reactivity of adenosylcobal-amin effect on coenzyme binding and catalysis of mutations in the conserved histidine-aspartate pair of glutamate mutase. Biochemistry 36 788497889. 

Reitzer, R., Gruber, K., Jogl, G., Wagner, U. G., Bothe, H., Buckel, W., and Kratky, C. 1999, Structure of coenzyme Bj2 dependent enzyme glutamate mutase from Clostridium cochlearium. Structure 7 8919902. 

Zelder, O., Beatrix, B., and Buckel, W., 1994, Cloning, sequencing and expression in Escherichia coli of the gene encoding component S of the coenzyme B12 -dependent glutamate mutase from Clostridium cochlearium. FEMS Microbiol. Lett. 118 15922. 

About 10 coenzyme B -dependent enzymes are now known (reviewed in References 13,14, and 76 see Table 1) four carbon skeleton mutases (methylmalonyl-CoA mutase (MMCM), glutamate mutase (GM), methylene glu-tarate mutase (MGM), isobutyryl-CoA mutase (ICM) ), diol dehydratase (DD), glycerol dehydratase, ethanol-amine anunonia lyase (EAL), two amino mutases, and Bi2-dependent ribonucleotide reductase. The coenzyme Bi2-dependent enzymes are unevenly distributed in the living world, and MMCM is the only enzyme that is also indispensable in human metabolism. ... 

Glutamate mutase. GM from Clostridium tetanomor-phum was the first enzyme discovered (around 1960) to be dependent upon a Bn-coenzyme. GM catalyzes the... 

Glutamate mutase the first coenzyme Bi2-dependent mutase... 

Glutamate mutase was discovered by Barker, who showed that the enzyme catalyzes the equilibration of (i j-glutamate with (25,36 )-3-methylaspaitate (Entry 1, Table 1 AG° = + 6.3 kJ mol K = 0.095) (for a review of glutamate mutase see Reference 7). This reaction is one of three distinct methods that nature uses to ferment glutamate to butyrate (5). Surprisingly, they all proceed through intermediate radicals. The coenzyme B 12-dependent fermentation is the only one of the three that... 

Co (B)2 coenzyme) Glutamate mutase, dioldehydrase, methionine synthetase... 

Huhta, M. S., Chen, FI. P., Hemann, C., Hille, C. R., Marsh, E. N. (2001) Protein-coenzyme interactions in adenosylcobalamin-dependent glutamate mutase, Biochem. J. 355, 131-137. 

Gruber, K., Reitzer, R., Kratky, C. (2001) Radical shuttling in a protein Ribose pseudorotation controls alkyl-radical transfer in the coenzyme B12 dependent enzyme glutamate mutase, Angew. Chem. Int. Ed. Engl. 40, 3377-3380. 

The enzymatic reactions in which adenosylcobalamin was known to serve as coenzyme by 1964 were those of glutamate mutase, methylmalonyl-CoA mutase (MCM), " propane-1,2-diol hydro-lyase (dioldehydrase, DDH), and glycerol hydro-lyase (glycerol dehydrase), shown in Equations (1)—(4). 

Enzymes catalyzing carbon skeleton rearrangements were the first to be recognized as coenzyme B 12-dependent. The first was glutamate mutase (GM), discovered in 1960, and the nature of the skeletal rearrangement in the reaction of GM inspired the identification of coenzyme B12 as the coenzyme for the apparently similar reaction of... 

Table I is a summary of all of the reactions known to date which require vitamin B12 coenzyme (i). The reaction catalyzed by glutamate mutase, the first reaction in which vitamin B12 was known to be involved, was discovered by Barker and his coworkers. The second reaction is the only one of these which also occurs in mammals all other reactions occur in bacteria. Much of the experimental data described here will be derived from the enzyme called dioldehydrase. An additional reaction which is not shown is the conversion of nucleotides to deoxynucleotides. The conversion of —CHOH— to — CH2— is in some way very similar to the reaction catalyzed by dioldehydrase. Vitamin B12 coenzyme-depend-...

The homologue of coenzyme B12 homocoenzyme B12 (27, Co -(5 -deoxy-5 -adenosylmethyl)-cob(in)alamin) has been recently examined as it has been suggested to fimction as a covalent structural mimic of the hypothetical enzyme bound activated state of the B -cofactor [62]. In the crystal structure of 27 the cobalt center was observed to be at a distance of 2.99 A from C5 of the homoadenosine moiety and the latter to be in the unusual syn-conformation. The crucial distance from the corrin-boimd cobalt center to the C5 of the homoadenosine moiety in 27 is, thus, roughly the same as found in one of the two activated forms of coenzyme B12 in the crystal structure of glutamate mutase [63]. 

The homolytic cleavage of the Co - C bond of the protein-boimd organo-metallic cofactor AdoCbl (2) is the initial step of the coenzyme Bi2-catalyzed enzymatic reactions. Halpern quoted that adenosyl cobamides can be considered as reversibly functioning sources for organic radicals [119]. A neutral aqueous solution of 2 is remarkably stable with a half-Ufe of 10 s (in the dark at room temperature), but decomposes, mainly with the homolysis of the Co-C bond, at higher temperatures [119,123]. The coenzyme B12-catalyzed enzyme reactions occur with maximal rates of approximately 100 s [173,239]. Rapid formation of Co(ll)corrins occurs only with addition of substrate to a solution of holoenzyme (or of apoenzymes and 2), as demonstrated in most of the known coenzyme Bi2-dependent enzymes, e.g., in methyl-malonyl-CoA mutase [121], glutamate mutase [202] and ribonucleotide reductase [239]. 

Coenzyme B12 is involved in wframolecular alkyl group transfer in the methylmalonyl-CoA isomerase and glutamate mutase reactions. (see reference I4), both of which may be schematically represented as ... 

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... 

Two views of the structure of the coenzyme Bi2-dependent enzyme glutamate mutase from Gostridium cochlearium, demonstrating binding with methylcobalamin (center of each molecule). 

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