Salivary proteolysis of histidine-rich polypeptides and the antifungal activity of peptide degradation products.
Incubation of purified synthetic histidine-rich polypeptides, HRP-2, -3, -4, -5, -6 (histatins), with diluted human parotid saliva yielded a series of peptide degradation products whose structures could be determined by gas-phase sequencing of cationic polyacrylamide gel electroblots. Sequencing indicated that two and sometimes three peptides were present in the same Coomassie blue-stained band. By comparing different individuals' salivas it was observed that structural variation occurs, perhaps due to differences in the concentrations or specific activities of salivary proteases. Based on the structural data, four proteolytic enzyme activities are proposed. A trypsin-like and chymotrypsin-like enzymatic activity(s) appear to represent the most active salivary protease; however, both an alanine-lysine endopeptidase and a histidine peptidase activity are also present in parotid saliva. In comparison to HRP-4 or HRP-6, degraded products were less active as antifungal agents against Candida albicans both in blastospore and germ-tube assays.
Department of Oral Biology and Pathology, State University of New York, Stony Brook 11794-8702.
L
L
Xu
K
K
Lal
R P
RP
Santarpia
J J
JJ
Pollock
D000595:Amino Acid Sequence; D000935:Antifungal Agents / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D002176:Candida albicans / Q000187:drug effects; D004591:Electrophoresis, Polyacrylamide Gel; D010450:Endopeptidases / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D006639:Histidine; D006801:Humans; D008969:Molecular Sequence Data; D010306:Parotid Gland / Q000378:metabolism; D010455:Peptides / Q000737:chemistry / Q000378:metabolism; D011506:Proteins / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D012463:Saliva / Q000201:enzymology*; D012471:Salivary Proteins and Peptides / Q000737:chemistry* / Q000378:metabolism / Q000502:physiology; D013172:Spores, Fungal / Q000187:drug effects; D000099053:Histidine-Rich Glycoprotein
D000935:Antifungal Agents; D010455:Peptides; D011506:Proteins; D012471:Salivary Proteins and Peptides; D000099053:Histidine-Rich Glycoprotein; D006639:Histidine; D010450:Endopeptidases