Synthetic and structural studies on Pyrularia pubera thionin: a single-residue mutation enhances activity against Gram-negative bacteria

FEBS Lett. 2003 Feb 11;536(1-3):215-9. doi: 10.1016/s0014-5793(03)00053-x.

Abstract

The thionin from Pyrularia pubera (Pp-TH), a 47-residue peptide with four internal disulfide bonds, was efficiently produced by chemical synthesis. Its antimicrobial activity in vitro against several representative pathogens (EC(50)=0.3-3.0 microM) was identical to that of natural Pp-TH. This peptide has a unique Asp(32) instead of the consensus Arg found in other thionins of the same family. In order to evaluate the effect of this mutation, the Arg(32) analogue (Pp-TH(D32R)) was also synthesized and showed a significant increase in antibiotic activity against several Gram-negative bacteria, whereas it retained the same activity against other pathogens. The overall structure of Pp-TH(D32R) was maintained, though a slight decrease in the helical content of the peptide was observed.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Anti-Bacterial Agents / chemical synthesis
  • Anti-Bacterial Agents / chemistry*
  • Anti-Bacterial Agents / pharmacology*
  • Antimicrobial Cationic Peptides
  • Circular Dichroism
  • Gram-Negative Bacteria / drug effects*
  • Models, Molecular
  • Molecular Sequence Data
  • Oxidation-Reduction
  • Peptides*
  • Plant Proteins / chemical synthesis
  • Plant Proteins / chemistry
  • Plant Proteins / genetics*
  • Plant Proteins / pharmacology*
  • Point Mutation
  • Sequence Alignment

Substances

  • Anti-Bacterial Agents
  • Antimicrobial Cationic Peptides
  • Peptides
  • Plant Proteins
  • THI1 protein, Pyrularia pubera