# Molecular Insights into the Heme‐Binding Potential of Plant NCR247‐Derived Peptides

## TL;DR

This paper explores how plant-derived NCR247 peptides bind to heme, revealing new insights into their potential therapeutic applications.

## Contribution

The study redefines the heme-binding capacity of NCR247-derived peptides using biochemical and computational methods.

## Key findings

- NCR247-derived peptides exhibit high-affinity heme-binding properties.
- Disulfide bonds in the peptides are critical for heme interaction.
- In silico studies support the biochemical observations of heme binding.

## Abstract

Heme is involved in many critical processes in pathogenic bacteria as iron acquisition by these microorganisms is achieved by either direct uptake of heme or use of heme‐binding proteins called hemophores. Exploring the underlying mechanisms on a molecular level can open new avenues in understanding the host‐pathogen interactions. Any imbalance of the heme concentration has a direct impact on the bacterial growth and survival. Thus, heme‐regulated proteins that are involved in heme homeostasis poise to be promising targets for research. Similarly, naturally occurring compounds, including cysteine‐rich peptides from either plant secondary metabolites or venom toxins from vertebrates and invertebrates, have been studied for their therapeutic potential. NCR247 is such a cysteine‐rich peptide, known to be crucial for nitrogenase activity in M. truncatula and its symbiotic relation with S. meliloti. NCR247‐derived peptides were suggested to serve as high‐affinity heme‐binding molecules with remarkable heme‐capturing properties. A comprehensive biochemical and computational analysis of NCR247‐derived peptides, however, redefines their heme‐binding capacity and consequently their potential therapeutic role.

Heme‐binding to Cys‐rich, plant‐derived NCR247 peptides was investigated using biochemical and bioanalytical approaches including UV/Vis and rRaman spectroscopy. The interaction of these disulfide‐bonded peptides plays a critical role in the binding mode with heme. The observations were further substantiated by in silico studies. This investigation redefines perceptions of the heme‐binding capacity of NCR247 peptides.