tailieunhanh - Báo cáo khoa học: Identification of crucial residues for the antibacterial activity of the proline-rich peptide, pyrrhocoricin

Members of the proline-rich antibacterial peptide family, pyrrhocoricin, apidaecin and drosocin appear to kill responsive bacterial species by binding to themultihelical lid region of the bacterial DnaK , the most potent among these peptides, is nontoxic to healthy mice, andcanprotect these animals frombacterial challenge. | Eur. J. Biochem. 269 4226-4237 2002 FEBS 2002 doi Identification of crucial residues for the antibacterial activity of the proline-rich peptide pyrrhocoricin Goran Kraaol1 Ralf Hoffmann2 Michael A Chatteraoon1. Sandor Lovas3 Mare Cudic1 Philinne Bulet4 B. Barry A. Condie1 K. Johan Rosengren5 Luis J. Montaner1 and Laszlo Otvos Jr1 1The Wistar Institute Philadelphia PA USA 2Biologisch-Medizinisches Forschungszentrum Heinrich-Heine-Universitat Dusseldorf Germany 3Department of Biomedical Sciences School of Medicine Creighton University Omaha NB USA 4Institut de Biologie Moleculaire et Cellulaire Strasbourg France 5Institute for Molecular Bioscience University of Queensland Brisbane Australia Members of the proline-rich antibacterial peptide family pyrrhocoricin apidaecin and drosocin appear to kill responsive bacterial species by binding to the multihelical lid region of the bacterial DnaK protein. yyri hocoricin. the most potent among these peptides is nontoxic to healthy mice and can protect these animals from bacterial challenge. A structure-antibacterial activity study of pyyyhocoyicin against Escherichia coli and Agrobacterium tumefaciens identified the N-terminal half residues 2-10 the region responsible for inhibition of the ATPase activity as the fragment that contains the active segment. While lldo-rescein-labeled versions of the native peptides entered E. coli cells deletion of the C-terminal half of pyyyhocoyicin significantly reduced the peptide s ability to enter bacterial or mammalian cells. Thie e íìndíngs highiighted py hocol icin s suitability for combating intracellular pathogens and raised the possibility that the proline-rich antibacterial peptides can deliver drug leads into mammalian cells. By observing strong relationships between the binding to a synthetic fragment of the target protein and antibacterial activities of pyrrhocori-cin analogs modified at strategic positions we further verified that DnaK was the .