Studies on histidine-rich polypeptides from human parotid saliva

Baum, Bruce J.; Bird, Janice L.; Millar, David B.; Longton, Robert W.

doi:10.1016/0003-9861(76)90455-0

Cited by 69 publications

(42 citation statements)

References 16 publications

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“…Histatin 7 is in fact a mixture of small histatins (histatins 7-12) that has been resolved into six components (see below). The nomenclature used for histatins described in this paper is consistent with the original observations on the electrophoretic mobility of histatins in the cationic PAGE system (Baum et al, 1976(Baum et al, , 1977.…”

Section: Methodssupporting

confidence: 68%

“…-Histatins were examined on 15% slab gels with use of a cationic sodium dodecylsulfate polyacrylamide gel electrophoresis (SDS-PAGE) system described previously (Baum et al, 1976(Baum et al, , 1977Oppenheim et al, 1988). The amino acid compositions of selected histatins and derived peptides were determined with use of a Beckman system 6300 amino acid analyzer following hydrolysis in 6 mol/L HCl for 22 h in vacuo at 1 100C.…”

Section: Methodsmentioning

confidence: 99%

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Structural Relationship Between Human Salivary Histatins

Troxler

Offner

Xu³

et al. 1990

J Dent Res

163

112

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Histatins are a group of electrophoretically distinct histidine-rich polypeptides with microbicidal activity found in human parotid and submandibular gland secretions. Recently, we have shown that histatins 1, 3, and 5 are homologous proteins that consist of 38, 32, and 24 amino acid residues, respectively, and that these polypeptides kill the pathogenic yeast, Candida albicans. We now describe the isolation and structural characterization of histatins 2, 4, 6, and 7-12, the remaining members ofthis group ofpolypeptides. Histatin 2 wasfound to be identical to the carboxyl terminal 26 residues of histatin 1; histatin 4 was found to be identical to the carboxyl terminal 20 residues of histatin 3; and histatin 6 was found to be identical to histatin 5, but contained an additional carboxyl terminal arginine residue. The amino acid sequences of histatins 7-12 formally correspond to residues 12-24, 13-24, 12-25, 13-25, 5-11, and 5-12, respectively, of histatin 3, but could also arise proteolytically from histatin 5 or 6. These results establish, for the first time, the complete structural relationships between all members of this group ofmicrobicidal proteins in human parotid saliva. The relationship of histatins to one another is discussed in the context of their genetic origin, biosynthesis and secretion into the oral cavity, and potential as reagents in anti-candidal studies.

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Section: Methodssupporting

confidence: 68%

Section: Methodsmentioning

confidence: 99%

Structural Relationship Between Human Salivary Histatins

Troxler

Offner

Xu³

et al. 1990

J Dent Res

163

112

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“…The gels were destained in the same solutions not containing the respective dyes until the band intensity was optimal relative to the background staining. These proteins have been demonstrated to be among the most sensitive to WS-associated proteolysis in prior studies (21,22,28,29). Fig.…”

Section: Methodsmentioning

confidence: 86%

“…These constituents comprise a variety of host and bacterial cells and their products as well as a serumlike gingival crevicular transudate. The nonexocrine compo-nents must contribute substantially to the enzymatic activity of whole saliva given the much lower proteolytic activities of pure salivary glandular secretions (4,6,21,22). Saliva is continuously being secreted (ϳ500 -1500 ml/day), thus providing a steady supply of newly synthesized salivary proteins to the oral cavity.…”

mentioning

confidence: 99%

Identification of Lys-Pro-Gln as a Novel Cleavage Site Specificity of Saliva-associated Proteases

Helmerhorst

Sun

Salih

et al. 2008

Journal of Biological Chemistry

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The nonsterile environment of the oral cavity facilitates substantial proteolytic processing, not only of resident salivary proteins but also of dietary proteins. To gain insight into whole saliva enzymatic processes, the in vivo generated peptides in this oral fluid were subjected to nano-flow liquid chromatography electrospray ionization tandem mass spectrometry. The 182 peptides identified were predominantly derived from acidic and basic proline-rich proteins, statherin, and histatins. The proteolytic cleavages in the basic proline-rich proteins occurred preferentially after a Gln residue with predominant specificity for the tripeptide Xaa-Pro-Gln, where Xaa in the P 3 position was mostly represented by Lys. Using the synthetic substrates LysPro-Gln-pNA and Gly-Gly-Gln-pNA, the overall K m values were determined to be 97 ؎ 7.7 and 611 ؎ 28 M, respectively, confirming glutamine endoprotease activity in whole saliva and the influence of the amino acids in positions P 2 and P 3 on protease recognition. The pH optimum of Lys-Pro-Gln-pNA hydrolysis was 7.0, and the activity was most effectively inhibited by antipain and 4-(2-aminoethyl) benzenesulfonyl fluoride, was metal ion-dependent, and not inhibited by cysteine protease inhibitors. A systematic evaluation of enzyme activities in various exocrine and nonexocrine contributors to whole saliva revealed that the glutamine endoprotease is derived from dental plaque and likely microbial in origin. The P 1 site being occupied by a Gln residue is a nonarchetype with respect to known proteases and indicates the presence of novel glutamine-specific endoprotease(s) in oral fluid.

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“…The existence of a group of small, cationic histidinerich polypeptides (histatins) in human saliva was first observed more than two decades ago by several groups of investigators (Bonilla, 1969;Azen, 1972;Balekjian and Longton, 1973;Holbrook and Molan, 1975;Baum et al, 1976). After their discovery, they were studied at the protein level and later at the molecular genetics level (genetic polymorphism, tissue distribution at the mRNA level, and the structure of the histatin genes).…”

Section: (I) Introductionmentioning

confidence: 99%

Human Salivary Histatins: Promising Anti-Fungal Therapeutic Agents

Tsai

Bobek

1998

Critical Reviews in Oral Biology & Medicine

142

115

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Histatins constitute a group of small, cationic multifunctional proteins present in the saliva of human and some nonhuman primates. The most significant function of histatins may be their anti-fungal activity against Candida albicans and Cryptococcus neoformans. Histatins have been extensively studied at both the protein and gene levels. The structure-function relationship of histatins with respect to their candidacidal activity has also been studied by means of recombinant histatin variants, as well as by chemically synthesized histatin fragments. The mechanism of histatins' action on Candida albicans is not clear, but it appears to be different from that of azole-based anti-fungal drugs which interrupt ergosterol synthesis. During the past 20 years, fungal infections have become more prevalent as a result of the emergence of AIDS, as well as, paradoxically, modern medical advances. The toxicity of current anti-fungal medicine, the emergence of drug-resistant strains, and the availability of only a few types of antifungal agents are the major disadvantages of current anti-fungal therapy. Therefore, the importance of the search for new, broadspectrum anti-fungals with little or no toxicity cannot be overemphasized. The following properties make histatins promising antifungal therapeutic agents: (1) They have little or no toxicity; (2) they possess high cidal activities against azole-resistant fungal species and most of the fungal species tested; and (3) their candidacidal activity is similar to that of azole-based antifungals.Current research efforts focus on the development of improved histatins with enhanced cidal activity and stability, and of suitable and effective histatin delivery systems. These and other approaches may help to outpace the growing list of drug-resistant and opportunistic fungi causing life-threatening, disseminating diseases. The histatins with improved protective properties may also be used as components of artificial saliva for patients with salivary dysfunction.

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Studies on histidine-rich polypeptides from human parotid saliva

Cited by 69 publications

References 16 publications

Structural Relationship Between Human Salivary Histatins

Structural Relationship Between Human Salivary Histatins

Identification of Lys-Pro-Gln as a Novel Cleavage Site Specificity of Saliva-associated Proteases

Human Salivary Histatins: Promising Anti-Fungal Therapeutic Agents

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