We have contributed to demonstrate that in diverse actinobacteria nitrogen metabolism is regulated by the signaling pathway that involves the protein kinase PknG. Both in the pathogen that causes tuberculosis in humans and in free-living species used in biotechnological processes, PknG controls the intracellular levels of glutamate in response the amino acids present in the medium. Notably, the integrity of this signal transduction pathway is critical for the virulence of Koch’s bacillus. In Mycobacterium, the GarA regulator modulates by direct interaction three metabolic enzymes, including a large glutamate dehydrogenase (L-GDH). This causes alpha-ketoglutarate to deviate from the Krebs cycle in favor of glutamate synthesis; instead, phosphorylation of GarA by PknG inhibits the action of the regulator and alpha-ketoglutarate is then directed to the Krebs cycle. We recently elucidated the 3D structure of the mycobacterial L-GDH modulated by GarA. These findings revealed unique aspects of the architecture of this enzyme type and suggest interesting regulatory mechanisms. A deep understanding of the molecular mechanisms involved in this signaling pathway will allow deciphering how M. tuberculosis and other actinobacteria modulate their metabolism and other key physiological processes. This will contribute to the design of drugs against tuberculosis and biotechnological innovations.