Glutamate mutase

The final B 12-dependent carbon-skeleton rearrangement to be discussed is catalyzed by glutamate mutase, which involves the interconversion of (5 glutamate and (25,35)-3-methylaspartate  

This reaction represents the first step in the fermentation of glutamate to acetate and butyrate in many clostridia [4, 80]. Once again, accepting the bound free-radical hypothesis leads to the following radical rearrangement  

As discussed for the previous two rearrangements, the carboxylate groups in 10 and 11 were replaced with hydrogen atoms and the computational problem reduces to investigating the rearrangement of the radical derived from propylamine [35]  

The crystal structure of GM from Cl. cochlearium has provided a detailed structural view of the enzyme, in which the corrinoid cofactor is boimd base- 

---

Theoretical studies that has investigated the homolysis step in different enzymatic systems [68-70] reveal that small models comprising only the corrin ring and two ligands are insufficient and that inclusion of more amino acids are essential to stabilize the radical intermediates. Recently, a QM/MM study of the initial phase of the glutamate mutase-catalyzed reaction found a large electrostatic stabilization by the surrounding protein [70], In our study of MCM we employed the ONIOM QM MM approach to reveal the role of the protein in the rupture of the Co—C5 bond [29],... 

This cobalamin-dependent enzyme [EC 5.4.99.1], also known as glutamate mutase or methylaspartate mutase, catalyzes the interconversion of L-r/ireo-3-methylaspar-tate and L-glutamate. 

METHYLASPARTATE AMMONIA-LYASE B-METHYLASPARTATE-GLUTAMATE MUTASE... 

Recently, EPR spectroscopy with 2H- and 13C-labeled glutamates as substrates for glutamate mutase permitted identification of a 4-glutamyl radical as a probable intermediate for that enzyme.402/402a/b... 

In both cases the reaction proceeds with retention of configuration at C-2 and with stereochemical specificity408 for one of the two hydrogens at C-l. The reaction catalyzed by methylmalonyl-CoA mutase likewise proceeds with retention of configuration at C-2 (Table 16-1)409 but the glutamate mutase reaction is accompanied by inversion (Eq. 16-28). 

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... 

Epimerization of sugar, mechanisms 778 Epimers, definition of 163 Epinephrine (adrenaline) 542,553, 553s Episomes. See plasmid Epithelial cells 29 Epitheliocytes 25 Epoxides, alkyation by 254 Epoxide hydrolases 591 EPR (electron paramagnetic resonance) spectroscopy 398, 399 of glutamate mutase 873 in study of phosphotransferases 639 EPSP (enolpyruvoylshikimate-3-phosphate) 687s... 

Glutamate dehydrogenase 770, 775 inhibition by 2-oxoglutarate 780 Glutamate mutase 871... 

In the present case an experimental approach to the elucidation of the steric course was facilitated by the observation that a cell-free extract from C. tetanomorphum contained not only the AdoCbl-dependent glutamate mutase, but also a specific ammonia lyase that catalysed the reversible interconversion of mesaconate (2) and (25,35 )-3-methylaspartate (3) (Fig. 4). In the presence of this... 

Fig. 4. The sequence of reactions that elucidated the steric course of the glutamate mutase reaction.

High-resolution struetural data have revealed that the finger print residues are key eomponents of a eonserved eorrinoid-binding domain. In the crystal structures of P. shermanii methylmalonyl-CoA mutase (Mancia and Evans, 1996 Mancia et al., 1998), C. cochlearium glutamate mutase... 

Substantial changes in protein structure also accompany cobala-min-binding, snapshots of which have been provided by high-resolution structural studies on glutamate mutase component S. The apo-fovm of C. tetanomorphum component S (Tollinger et al., 1998) and a CNCbl-... 

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. 

---