Identification of CG-1, a natural peptide antibiotic derived from human neutrophil cathepsin G.
Cathepsin G is a neutral serine protease of the granzyme B family which is found in human PMN, cells known to be important in the defense of the periodontium against periodontal bacteria. We propose that cathepsin G serves as a "pro-antibiotic" containing peptide domains which express selective antibiotic properties. In this study, we used HPLC to separate the low-molecular-weight peptides derived from the ultrafiltrate of a granule extract from unstimulated PMN. One of the peptides exhibited intense bactericidal activity as determined by radial diffusion overlay assay (against Escherichia coli ML-35P), an amino-terminal sequence "RVSSFLPWIR...", and a 3.1-kDa molecular mass determined by electrospray ionization-mass spectrometry. The sequence and mass are consistent with the C-terminus of cathepsin G deduced by cDNA analysis. These findings support the hypothesis that antibiotic peptides derived from cathepsin G occur naturally in human PMN. Since this is the first naturally occurring antibiotic peptide derived from cathepsin G, we designate it "CG-1".
Miyasaki
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Section of Oral Biology (63-050 CHS) and Dental Research Institute, University of California at Los Angeles, School of Dentistry 90024, USA.
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Harwig
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Lehrer
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D000595:Amino Acid Sequence; D000900:Anti-Bacterial Agents / Q000032:analysis / Q000096:biosynthesis*; D001426:Bacterial Proteins / Q000737:chemistry; D001798:Blood Proteins / Q000096:biosynthesis* / Q000737:chemistry; D056649:Cathepsin G; D002403:Cathepsins / Q000737:chemistry*; D003594:Cytoplasmic Granules / Q000737:chemistry; D006801:Humans; D008565:Membrane Proteins; D008969:Molecular Sequence Data; D009504:Neutrophils / Q000737:chemistry* / Q000166:cytology; D010455:Peptides; D011355:Prodrugs; D012697:Serine Endopeptidases
D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D001798:Blood Proteins; C088547:KTN1 protein, human; D008565:Membrane Proteins; D010455:Peptides; D011355:Prodrugs; D002403:Cathepsins; D012697:Serine Endopeptidases; C534094:CTSG protein, human; D056649:Cathepsin G