Glutamate mutase (GLM)

Glutamate mutase is a coenzyme B12-dependent enzyme that catalyzes the reversible conversion of L-glutamate to L-threo-3-methylaspartate (UniProt: P80077). This enzyme is essential for the fermentation of glutamate in various anaerobic bacteria, such as Clostridium cochlearium and Clostridium tetanomorphum (PubMed: 10496863). Structurally, it is a heterotetramer consisting of two subunits, typically referred to as the large (MutL) and small (MutS) components, which together form the active site (PubMed: 10529339). The catalytic mechanism involves the homolysis of the cobalt-carbon bond of adenosylcobalamin to generate a 5'-deoxyadenosyl radical, which then abstracts a hydrogen atom from the substrate to initiate rearrangement (PubMed: 10677338). While not a direct target for current clinical drugs, it is a significant model for studying radical enzymes and is frequently explored in computational docking studies to understand substrate specificity and transition state stabilization. Its role in bacterial metabolism makes it a potential target for antimicrobial development against specific anaerobic pathogens, though care must be taken to avoid cross-reactivity with human B12-dependent enzymes like methylmalonyl-CoA mutase.

Other names

Glutamate isomeraseL-glutamate 2,3-methylmutase

Radical-mediated carbon-skeleton rearrangement using a 5'-deoxyadenosylcobalamin cofactor