NCR247

NCR247 is a defensin-like nodule cysteine-rich (NCR) peptide and a heme chelator. It induces iron starvation responses in Sinorhizobium meliloti and Medicago truncatula while supporting nitrogenase activity. NCR247 is applicable in research related to periodontal disease and toxoplasmosis.

NCR247 is a compound that binds to heme with nanomolar affinity, facilitated by cysteine residues, the C10P11 motif, and tyrosine residues. Its D enantiomer and the Medicago truncatula homolog retain significant nanomolar heme binding affinity. NCR247 at a concentration of 5 μM for 16 minutes can chelate heme and inhibit its inherent peroxidase activity, preventing its biological utilization. At 2-4 μM for 30-60 minutes, NCR247 induces an iron starvation response in S. meliloti by upregulating iron uptake genes and downregulating rirA expression; this response requires BacA for NCR247 transport to the bacterial cytoplasm and is mediated by the Irr regulatory pathway. At 2 μM for 30-60 minutes, NCR247 enhances iron ion import into S. meliloti, increasing total cellular iron content through the Irr-mediated pathway. L-NCR247 and D-NCR247, at 2.5-20 μM for 24-48 hours, inhibit the growth of heme-deficient pathogens Haemophilus influenzae and Porphyromonas gingivalis, with D-NCR247 exhibiting stronger activity than L-NCR247. This growth inhibition can be reversed by heme addition, confirming that heme chelation is the mechanism of action. Furthermore, L-NCR247 and D-NCR247 at concentrations of 25-150 μM for 6 hours inhibit Toxoplasma gondii plaque formation in human foreskin fibroblasts in a concentration-dependent manner, relying on heme binding.

NCR247 (endogenous expression; 2 μM; in vitro treatment) is essential for the effective symbiosis between legumes and rhizobia. The absence of NCR247 reduces iron content in root nodules and disrupts normal nodule development, while exogenous NCR247 can enhance iron uptake in symbiotic bacteroids.