title: Indolicidin targets duplex DNA: structural and mechanistic insight through a combination of spectroscopy and microscopy.
abstract: 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.
authors.affiliation: Department of Biophysics, Bose Institute, P-1/12 CIT Scheme VII (M), Kolkata 700054 (India).
authors.forename: Anirban
authors.initials: A
authors.lastname: Ghosh
authors.forename: Rajiv Kumar
authors.initials: RK
authors.lastname: Kar
authors.forename: Jagannath
authors.initials: J
authors.lastname: Jana
authors.forename: Abhijit
authors.initials: A
authors.lastname: Saha
authors.forename: Batakrishna
authors.initials: B
authors.lastname: Jana
authors.forename: Janarthanan
authors.initials: J
authors.lastname: Krishnamoorthy
authors.forename: Dinesh
authors.initials: D
authors.lastname: Kumar
authors.forename: Surajit
authors.initials: S
authors.lastname: Ghosh
authors.forename: Subhrangsu
authors.initials: S
authors.lastname: Chatterjee
authors.forename: Anirban
authors.initials: A
authors.lastname: Bhunia
mesh_terms: D000890:Anti-Infective Agents / Q000494:pharmacology*; D023181:Antimicrobial Cationic Peptides / Q000378:metabolism / Q000494:pharmacology*; D001419:Bacteria / Q000187:drug effects / Q000378:metabolism; D045744:Cell Line, Tumor; D004261:DNA Replication / Q000187:drug effects; D004269:DNA, Bacterial / Q000187:drug effects*; D006801:Humans; D009682:Magnetic Resonance Spectroscopy
chemical_list: D000890:Anti-Infective Agents; D023181:Antimicrobial Cationic Peptides; D004269:DNA, Bacterial; C073143:indolicidin
keywords: AMP; NMR spectroscopy; duplex DNA; indolicidin; molecular dynamics