{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T19:32:37Z","timestamp":1789414357696,"version":"build-2803163510"},"reference-count":38,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2015,5,11]],"date-time":"2015-05-11T00:00:00Z","timestamp":1431302400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["30572037"],"award-info":[{"award-number":["30572037"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["81470753"],"award-info":[{"award-number":["81470753"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100004826","name":"Beijing Natural Science Foundation","doi-asserted-by":"crossref","award":["7062028"],"award-info":[{"award-number":["7062028"]}],"id":[{"id":"10.13039\/501100004826","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100004826","name":"Beijing Natural Science Foundation","doi-asserted-by":"crossref","award":["7122078"],"award-info":[{"award-number":["7122078"]}],"id":[{"id":"10.13039\/501100004826","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecular Oral Microbiology"],"published-print":{"date-parts":[[2015,10]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p><jats:italic>Porphyromonas gingivalis (P. gingivalis)<\/jats:italic> is a major etiological agent in the development and progression of chronic periodontitis. It produces cysteine proteases (gingipains), including a lysine\u2010specific gingipain and two arginine\u2010specific gingipains. Heme binding and uptake are fundamental to the growth and virulence of <jats:italic>P.\u00a0gingivalis<\/jats:italic>. The recombinant hemagglutinin 2 domain (<jats:styled-content style=\"fixed-case\">rHA<\/jats:styled-content>2) of gingipain binds hemin with high affinity. The aim of the present work was to identify the key residues involved in its hemin\u2010binding activity. A functional <jats:styled-content style=\"fixed-case\">rHA<\/jats:styled-content>2 was expressed and bound to hemin\u2010agarose, and then digested with endopeptidases. The peptides bound to hemin\u2010agarose were identified by mass spectrometry and the amino acids were assessed by mutation and peptide binding inhibition analysis. The <jats:styled-content style=\"fixed-case\">DHYAVMISK<\/jats:styled-content> sequence was identified in peptides derived from both Asp\u2010N and Lys\u2010C endopeptidase digestions of <jats:styled-content style=\"fixed-case\">rHA<\/jats:styled-content>2. A monoclonal antibody, <jats:styled-content style=\"fixed-case\">mA<\/jats:styled-content>b <jats:styled-content style=\"fixed-case\">QB<\/jats:styled-content>, was produced and its epitope was associated with the <jats:styled-content style=\"fixed-case\">DGFPGDHYAVMISK<\/jats:styled-content> peptide within the <jats:styled-content style=\"fixed-case\">HA<\/jats:styled-content>2 domain. Hemin was shown to competitively inhibit the immunoreactivity of <jats:styled-content style=\"fixed-case\">rHA<\/jats:styled-content>2 or the peptide to <jats:styled-content style=\"fixed-case\">mA<\/jats:styled-content>b <jats:styled-content style=\"fixed-case\">QB<\/jats:styled-content>. The peptide <jats:styled-content style=\"fixed-case\">DHYAVMISK<\/jats:styled-content> inhibited hemin\u2010binding activity; although, this inhibition was not seen when the peptide contained the H1001E mutation (<jats:styled-content style=\"fixed-case\">DEYAVMISK<\/jats:styled-content>). Based on these results, we propose that residue His1001 is involved in the hemin\u2010binding mechanism of the <jats:italic>P.\u00a0gingivalis <\/jats:italic><jats:styled-content style=\"fixed-case\">rHA<\/jats:styled-content>2 and the peptide containing this residue, <jats:styled-content style=\"fixed-case\">DHYAVMISK<\/jats:styled-content>, may be an inhibitor of hemin binding.<\/jats:p>","DOI":"10.1111\/omi.12097","type":"journal-article","created":{"date-parts":[[2015,4,1]],"date-time":"2015-04-01T18:48:14Z","timestamp":1427914094000},"page":"337-346","source":"Crossref","is-referenced-by-count":8,"title":["Identification of amino acid residues involved in hemin binding in <i><scp>P<\/scp>orphyromonas gingivalis<\/i> hemagglutinin 2"],"prefix":"10.1111","volume":"30","author":[{"given":"Q.B.","family":"Yang","sequence":"first","affiliation":[{"name":"Beijing Institute for Dental Research Beijing Stomatological Hospital and School of Stomatology Capital Medical University Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F.Y.","family":"Yu","sequence":"additional","affiliation":[{"name":"Beijing Institute for Dental Research Beijing Stomatological Hospital and School of Stomatology Capital Medical University Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L.","family":"Sun","sequence":"additional","affiliation":[{"name":"Beijing Institute for Dental Research Beijing Stomatological Hospital and School of Stomatology Capital Medical University Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Q.X.","family":"Zhang","sequence":"additional","affiliation":[{"name":"Beijing Institute for Dental Research Beijing Stomatological Hospital and School of Stomatology Capital Medical University Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Lin","sequence":"additional","affiliation":[{"name":"Beijing Institute for Dental Research Beijing Stomatological Hospital and School of Stomatology Capital Medical University Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"X.Y.","family":"Geng","sequence":"additional","affiliation":[{"name":"Beijing Institute for Dental Research Beijing Stomatological Hospital and School of Stomatology Capital Medical University Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"X.N.","family":"Sun","sequence":"additional","affiliation":[{"name":"Beijing Institute for Dental Research Beijing Stomatological Hospital and School of Stomatology Capital Medical University Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.L.","family":"Li","sequence":"additional","affiliation":[{"name":"Beijing Institute for Dental Research Beijing Stomatological Hospital and School of Stomatology Capital Medical University Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Y.","family":"Liu","sequence":"additional","affiliation":[{"name":"Beijing Institute for Dental Research Beijing Stomatological Hospital and School of Stomatology Capital Medical University Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2015,5,11]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1574-6968.1995.tb07915.x"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.patbio.2006.07.045"},{"key":"e_1_2_6_4_1","doi-asserted-by":"crossref","first-page":"23033","DOI":"10.1016\/S0021-9258(18)54459-8","article-title":"Involvement of the distal histidine in the low affinity exhibited by Hb Chico (Lys beta 66 \u2013 Thr) and its isolated beta chains","volume":"266","author":"Bonaventura C.","year":"1991","journal-title":"J Biol 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PhD dissertation William Marsh Rice University Houston TX. 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