Mechanism of 2-oxoglutarate signaling by the Synechococcus elongatus P^sub II^ signal transduction protein

... proteins control key processes of nitrogen metabolism in bacteria, archaea, and plants in response to the central metabolites ATP, ADP, and 2-oxoglutarate (2-OG), signaling cellular energy and carbon and nitrogen abundance. This metabolic information is integrated by ...and transmitted to regulatory targets (key enzymes, transporters, and transcription factors), modulating their activity. In oxygenic phototrophs, the controlling enzyme of arginine synthesis, N-acetyl-glutamate kinase (NAGK), is a major ... target, whose activity responds to 2-OG via PII. Here we show structures of the Synechococcus elongatus ... protein in complex with ATP, ..., and 2-OG, which clarify how 2-OG affects ...- NAGK interaction. ... trimers with all three sites fully occupied were obtained as well as structures with one or two 2-OG molecules per ... trimer. These structures identify the site of 2-OG located in the vicinity between the subunit clefts and the base of the T loop. The 2-OG is bound to a ... ion, which is coordinated by three phosphates of ATP, and by ionic interactions with the highly conserved residues K58 and Q39 together with B- and T-loop backbone interactions. These interactions impose a unique T-loop conformation that affects the interactions with the ... target. Structures of PII trimers with one or two bound 2-OG molecules reveal the basis for anticooperative 2-OG binding and shed light on the intersubunit signaling mechanism by which PII senses effectors in a wide range of concentrations. (ProQuest: ... denotes formulae/symbols omitted.)