Bactericidal activity of a synthetic peptide (CG 117-136) of human lysosomal cathepsin G is dependent on arginine content.
The importance of individual amino acids in mediating the broad-spectrum bactericidal action of a 20-mer amphipathic, cationic peptide (CG 117-136) of human lysosomal cathepsin G was determined by using a single amino acid replacement strategy. This strategy revealed an important role for arginine because loss of any of the four arginine residues in CG 117-136 due to substitution with alanine, citrulline, or lysine residues resulted in a reduction of its bactericidal activity against both Pseudomonas aeruginosa ATCC 27853 and Staphylococcus aureus ATCC 33593. However, the replacement of a single alanine residue in CG 117-136 with arginine, but not glutamic acid, enhanced the activity of CG 117-136 against both P. aeruginosa and S. aureus. The importance of certain bulky, nonpolar amino acids for the bactericidal activity of CG 117-136 was also evident, since their substitutions by alanine diminished bactericidal activity. Accordingly, contributions of hydrophobic amino acids and structural considerations of the guanidinium side chain of arginine are major determinants in the broad-spectrum antimicrobial action of CG 117-136.
Laboratories of Microbial Pathogenesis, Research Service, Department of Veterans Affairs Medical Center, Decatur, Georgia 30033, USA. wshafer@unix.cc.emory.edu.
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Shafer
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Hubalek
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Huang
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Pohl
D000595:Amino Acid Sequence; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology*; D001120:Arginine / Q000032:analysis*; D056649:Cathepsin G; D002403:Cathepsins / Q000737:chemistry*; D015169:Colony Count, Microbial; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D008247:Lysosomes / Q000201:enzymology*; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry / Q000494:pharmacology*; D011506:Proteins / Q000737:chemistry / Q000494:pharmacology*; D011550:Pseudomonas aeruginosa / Q000187:drug effects*; D012697:Serine Endopeptidases; D013211:Staphylococcus aureus / Q000187:drug effects*
D000900:Anti-Bacterial Agents; C102462:CG 117136; D036341:Intercellular Signaling Peptides and Proteins; D010455:Peptides; D011506:Proteins; D001120:Arginine; D002403:Cathepsins; D012697:Serine Endopeptidases; C534094:CTSG protein, human; D056649:Cathepsin G