{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T04:02:50Z","timestamp":1791172970503,"version":"4.1.0"},"reference-count":49,"publisher":"American Society for Microbiology","issue":"3","license":[{"start":{"date-parts":[[2001,3,1]],"date-time":"2001-03-01T00:00:00Z","timestamp":983404800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Infect Immun"],"published-print":{"date-parts":[[2001,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            One of the salient features of periodontitis and gingivitis is the increase in the levels of bacterial and host-derived proteolytic enzymes in oral inflammatory exudates. This study evaluated the potential of histatin 5, a 24-residue histidine-rich salivary antimicrobial protein, to inhibit these enzymes. Using biotinylated gelatin as a substrate, histatin 5 was found to inhibit the activity of the host matrix metalloproteinases MMP-2 and MMP-9 with 50% inhibitory concentrations (IC\n            <jats:sub>50<\/jats:sub>\n            s) of 0.57 and 0.25 \u03bcM, respectively. To localize the domain responsible for this inhibition, three peptides containing different regions of histatin 5 were synthesized and tested as inhibitors of MMP-9. Peptides comprising residues 1 to 14 and residues 4 to 15 of histatin 5 showed much lower inhibitory activities (IC\n            <jats:sub>50<\/jats:sub>\n            , 21.4 and 20.5 \u03bcM, respectively), while a peptide comprising residues 9 to 22 showed identical activity to histatin 5 against MMP-9. These results point to a functional domain localized in the C-terminal part of histatin 5. To evaluate the effect of histatin 5 on bacterial proteases, a detailed characterization of histatin 5 inhibition of gingipains from\n            <jats:italic>Porphyromonas gingivalis<\/jats:italic>\n            was carried out using purified Arg- and Lys-specific enzymes. Kinetic analysis of the inhibition of the Arg-gingipain revealed that histatin 5 is a competitive inhibitor, affecting only the\n            <jats:italic>\n              K\n              <jats:sub>m<\/jats:sub>\n            <\/jats:italic>\n            with a\n            <jats:italic>\n              K\n              <jats:sub>i<\/jats:sub>\n            <\/jats:italic>\n            of 15 \u03bcM. In contrast, inhibition of Lys-gingipain affected both the\n            <jats:italic>\n              K\n              <jats:sub>m<\/jats:sub>\n            <\/jats:italic>\n            and\n            <jats:italic>V<\/jats:italic>\n            <jats:sub>max<\/jats:sub>\n            , suggesting that both competitive and noncompetitive competitive processes underlie this inhibition. The inhibitory activity of histatin 5 against host and bacterial proteases at physiological concentrations points to a new potential biological function of histatin in the oral cavity.\n          <\/jats:p>","DOI":"10.1128\/iai.69.3.1402-1408.2001","type":"journal-article","created":{"date-parts":[[2002,7,27]],"date-time":"2002-07-27T10:01:19Z","timestamp":1027764079000},"page":"1402-1408","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":103,"title":["Salivary Histatin 5 Is an Inhibitor of Both Host and Bacterial Enzymes Implicated in Periodontal Disease"],"prefix":"10.1128","volume":"69","author":[{"given":"Heloisa","family":"Gusman","sequence":"first","affiliation":[{"name":"<!--label omitted: 1-->Department of Periodontology and Oral Biology, Boston University Goldman School of Dental Medicine,1 and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James","family":"Travis","sequence":"additional","affiliation":[{"name":"<!--label omitted: 2-->Department of Biochemistry, University of Georgia, Athens, Georgia2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eva J.","family":"Helmerhorst","sequence":"additional","affiliation":[{"name":"<!--label omitted: 1-->Department of Periodontology and Oral Biology, Boston University Goldman School of Dental Medicine,1 and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan","family":"Potempa","sequence":"additional","affiliation":[{"name":"<!--label omitted: 2-->Department of Biochemistry, University of Georgia, Athens, Georgia2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert F.","family":"Troxler","sequence":"additional","affiliation":[{"name":"<!--label omitted: 1-->Department of Periodontology and Oral Biology, Boston University Goldman School of Dental Medicine,1 and"},{"name":"<!--label omitted: 3-->Department of Biochemistry, Boston University School of Medicine,3 Boston, Massachusetts, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank G.","family":"Oppenheim","sequence":"additional","affiliation":[{"name":"<!--label omitted: 1-->Department of Periodontology and Oral Biology, Boston University Goldman School of Dental Medicine,1 and"},{"name":"<!--label omitted: 3-->Department of Biochemistry, Boston University School of Medicine,3 Boston, Massachusetts, and"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","first-page":"41","article-title":"Elevation of salivary antimicrobial proteins following HIV-1 infection","volume":"3","author":"Atkinson J. 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G.\nSalivary antimicrobials: where are we?\nCariology for the nineties.\nBowen\nW. H.\nTabak\nL. A.\n1993\n117\n131\nUniversity of Rochester Press\nRochester N.Y"}],"container-title":["Infection and Immunity"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/IAI.69.3.1402-1408.2001","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/IAI.69.3.1402-1408.2001","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,3,5]],"date-time":"2022-03-05T02:07:27Z","timestamp":1646446047000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/IAI.69.3.1402-1408.2001"}},"subtitle":[],"editor":[{"given":"J. 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