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Indolicidin (IR13), a 13-residue antimicrobial peptide from the cathelicidin family, is known to exhibit a broad spectrum of antimicrobial activity against various microorganisms. This peptide inhibits bacterial DNA synthesis resulting in cell filamentation. However, the precise mechanism remains unclear and requires further investigation. The central PWWP motif of IR13 provides a unique structural element that can wrap around, and thus stabilize, duplex B-type DNA structures. Replacements of the central Trp-Trp pair with Ala-Ala, His-His, or Phe-Phe residues in the PxxP motif significantly affects the ability of the peptide to stabilize duplex DNA. Results of microscopy studies in conjunction with spectroscopic data confirm that the DNA duplex is stabilized by IR13, thereby inhibiting DNA replication and transcription. In this study we provide high-resolution structural information on the interaction between indolicidin and DNA, which will be beneficial for the design of novel therapeutic antibiotics based on peptide scaffolds.

Mutations in the genome are responsible for several fatal genetic disorders. The default DNA repair mechanism restores the malfunction of the gene caused by mutation to maintain functional regularity and sequential integrity of the cell. Here, we have elucidated the NMR structure and the dynamics of GC mismatched DNA (PDB code: 2MJX) and found that the mismatched DNA still retains the typical B-type helical form, but in the process introduces backbone distortion resulting from frame-shifted base pairs.