Crystal structure of the 2-iminoglutarate-bound complex of glutamate dehydrogenase from Corynebacterium glutamicum

The NADP(+) -dependent glutamate dehydrogenase from Corynebacterium glutamicum (CgGDH) is considered to be one of the key enzymes in the industrial fermentation of glutamate due to its high glutamate-producing activity. We determined the crystal structure of CgGDH complexed with NADP(+) and 2-iminoglutarate. Among six subunits of hexameric CgGDH-binding NADP(+), only four subunits bind 2-iminoglutarate in a closed form, while the other two are in an open form. In the closed form, 2-iminoglutarate is bound to the substrate-binding site with the 2-imino group stacked by the nicotinamide ring of the coenzyme, suggesting a prehydride transfer state in a hypothesized reaction scheme with the imino intermediate. We also conducted MD simulations and provide insights into the extreme preference for the glutamate-producing reaction of CgGDH. Database The atomic coordinate and structure factors have been deposited in the RCSB PDB database under the accession number 5GL-D.