The activity of the ribonucleotide monophosphatase UmpH is controlled by interaction with the GlnK signaling protein in Escherichia coli.

The PII signaling proteins are ubiquitous in prokaryotes serving as crucial metabolic hubs in different metabolic pathways because of their ability to sense and integrate signals of the cellular nitrogen, carbon, and energy levels. In this study, we used ligand fishing assays to identify the ribonucleotide monophosphatase UmpH enzyme as a novel target of the PII signaling protein GlnK in Escherichia coli. In vitro analyses showed that UmpH interacts specifically with the PII protein GlnK but not with its paralog protein GlnB. The UmpH-GlnK complex is modulated by the GlnK uridylylation status and by the levels of the GlnK allosteric effectors ATP, ADP, and 2-oxoglutarate. Upon engaging interaction with GlnK, UmpH becomes less active toward its substrate uridine 5'-monophosphate. We suggest a model where GlnK will physically interact to reduce the UmpH activity during the transition from N-starvation to N-sufficient conditions. Such a mechanism may help the cells to reprogram the fate of uridine 5'-monophosphate from catabolism to anabolism avoiding futile cycling of key nutrients.