Synthetic and structural studies on Pyrularia pubera thionin: a single-residue mutation enhances activity against Gram-negative bacteria.
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.
Vila-Perelló
Miquel
M
Department of Experimental and Health Sciences, Pompeu Fabra University, Dr. Aiguader 80, E-08003 Barcelona, Spain.
Sánchez-Vallet
Andrea
A
García-Olmedo
Francisco
F
Molina
Antonio
A
Andreu
David
D
D000595:Amino Acid Sequence; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D023181:Antimicrobial Cationic Peptides; D002942:Circular Dichroism; D006090:Gram-Negative Bacteria / Q000187:drug effects*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010084:Oxidation-Reduction; D010455:Peptides; D010940:Plant Proteins / Q000138:chemical synthesis / Q000737:chemistry / Q000235:genetics* / Q000494:pharmacology*; D017354:Point Mutation; D016415:Sequence Alignment
D000900:Anti-Bacterial Agents; D023181:Antimicrobial Cationic Peptides; D010455:Peptides; D010940:Plant Proteins; C044942:THI1 protein, Pyrularia pubera