title: Histatin 5 is a substrate and not an inhibitor of the Arg- and Lys-specific proteinases of Porphyromonas gingivalis.
abstract: The salivary peptide histatin 5 has been reported to be an inhibitor of the Arg- and Lys-specific proteinases of Porphyromonas gingivalis, an oral pathogen associated with periodontitis. In this study a purified P. gingivalis proteinase preparation consisting of a complex of the Arg- and Lys-specific proteinases and adhesins was assayed using chromogenic substrates in the presence of histatin 5. Histatin 5 produced a concentration-dependent decrease in the initial rate of hydrolysis of the chromogenic substrates by both proteinases. However, pre-incubation of histatin 5 with the purified proteinase preparation or a P. gingivalis cell sonicate for 10 min prior to assay with the chromogenic substrates showed that under these conditions the salivary peptide did not decrease the initial rate of chromogen release. Mass spectrometric analysis revealed rapid degradation of histatin 5 at all four lysyl and all three arginyl residues by the P. gingivalis proteinases. This study demonstrates that histatin 5 is a substrate for the P. gingivalis extracellular Arg- and Lys-specific cysteine proteinases and not an inhibitor.
authors.affiliation: Biochemistry and Molecular Biology Unit, School of Dental Science, University of Melbourne, Australia.
authors.forename: N M
authors.initials: NM
authors.lastname: O'Brien-Simpson
authors.forename: S G
authors.initials: SG
authors.lastname: Dashper
authors.forename: E C
authors.initials: EC
authors.lastname: Reynolds
mesh_terms: D000595:Amino Acid Sequence; D001665:Binding Sites / Q000235:genetics; D010450:Endopeptidases / Q000378:metabolism*; D054808:Histatins; D006801:Humans; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry / Q000378:metabolism; D016966:Porphyromonas gingivalis / Q000201:enzymology*; D012471:Salivary Proteins and Peptides / Q000235:genetics / Q000378:metabolism*; D013379:Substrate Specificity
chemical_list: C068075:HTN3 protein, human; D054808:Histatins; D010455:Peptides; D012471:Salivary Proteins and Peptides; D010450:Endopeptidases