{"@context":{"@vocab":"https://cir.nii.ac.jp/schema/1.0/","rdfs":"http://www.w3.org/2000/01/rdf-schema#","dc":"http://purl.org/dc/elements/1.1/","dcterms":"http://purl.org/dc/terms/","foaf":"http://xmlns.com/foaf/0.1/","prism":"http://prismstandard.org/namespaces/basic/2.0/","cinii":"http://ci.nii.ac.jp/ns/1.0/","datacite":"https://schema.datacite.org/meta/kernel-4/","ndl":"http://ndl.go.jp/dcndl/terms/","jpcoar":"https://github.com/JPCOAR/schema/blob/master/2.0/"},"@id":"https://cir.nii.ac.jp/crid/1362825895596004480.json","@type":"Article","productIdentifier":[{"identifier":{"@type":"DOI","@value":"10.1139/o07-073"}},{"identifier":{"@type":"URI","@value":"https://cdnsciencepub.com/doi/full-xml/10.1139/O07-073"}},{"identifier":{"@type":"URI","@value":"https://cdnsciencepub.com/doi/pdf/10.1139/O07-073"}}],"dc:title":[{"@value":"Apolactoferrin inhibits the catalytic domain of matrix metalloproteinase-2 by zinc chelation"}],"description":[{"type":"abstract","notation":[{"@value":"<jats:p> Lactoferrin (LTF) is a multifunctional iron-binding protein that is also capable of binding other divalent metal cations, especially Zn<jats:sup>2+</jats:sup>. Recent investigations indicate that lactoferrin levels are elevated in many disease conditions in which matrix metalloproteinases (MMPs), particularly MMP-2, are also elevated, suggesting that the 2 proteins may interact. This possibility was examined by determining the effect of LTF in its holo (metal-bound) and apo (metal-free) forms on the proteolytic activity of MMP-2 and other similar zinc metalloproteases. Pre-incubation with apolactoferrin, but not hololactoferrin, greatly reduced the hydrolysis of a peptide substrate by MMP-2, but not by MMP-1, -8, -9, or -13. This inhibition was specific for the 42 kDa catalytic domain fragment of MMP-2 lacking the hemopexin domain, since the 66 kDa form was poorly inhibited by apolactoferrin. The inhibition of the MMP-2 catalytic domain was strongly temperature sensitive, indicating that the conformation of one or both proteins is crucial to this interaction. To ascertain the mechanism of inhibition, increasing concentrations of ZnCl<jats:sub>2</jats:sub> and FeCl<jats:sub>2</jats:sub> were added to the reaction. While addition of Fe<jats:sup>2+</jats:sup> did not reverse inhibition, the addition of Zn<jats:sup>2+</jats:sup> resulted in a recovery of MMP-2 activity, and furthermore, zinc-saturated LTF did not inhibit MMP-2. Together, these data strongly suggest that apolactoferrin is capable of removing the catalytic zinc from the active site of MMP-2, although an exosite-based interaction between the 2 proteins cannot be fully ruled out. This inhibitory activity suggests a novel function for LTF and may represent a novel regulatory mechanism that regulates proteolysis by MMP-2 in vivo. </jats:p>"}]}],"creator":[{"@id":"https://cir.nii.ac.jp/crid/1382825895596004482","@type":"Researcher","foaf:name":[{"@value":"Anthony L. Newsome"}],"jpcoar:affiliationName":[{"@value":"Department of Biology, Middle Tennesee State University, 1301 E. Main Street, Murfreesboro, TN 37132, USA."}]},{"@id":"https://cir.nii.ac.jp/crid/1382825895596004480","@type":"Researcher","foaf:name":[{"@value":"Jon Paul Johnson"}],"jpcoar:affiliationName":[{"@value":"Department of Biology, Middle Tennesee State University, 1301 E. Main Street, Murfreesboro, TN 37132, USA."}]},{"@id":"https://cir.nii.ac.jp/crid/1382825895596004481","@type":"Researcher","foaf:name":[{"@value":"Rebecca L. Seipelt"}],"jpcoar:affiliationName":[{"@value":"Department of Biology, Middle Tennesee State University, 1301 E. Main Street, Murfreesboro, TN 37132, USA."}]},{"@id":"https://cir.nii.ac.jp/crid/1382825895596004483","@type":"Researcher","foaf:name":[{"@value":"Michael W. Thompson"}],"jpcoar:affiliationName":[{"@value":"Department of Biology, Middle Tennesee State University, 1301 E. Main Street, Murfreesboro, TN 37132, USA."}]}],"publication":{"publicationIdentifier":[{"@type":"PISSN","@value":"08298211"},{"@type":"EISSN","@value":"12086002"}],"prism:publicationName":[{"@value":"Biochemistry and Cell Biology"}],"dc:publisher":[{"@value":"Canadian Science Publishing"}],"prism:publicationDate":"2007-10","prism:volume":"85","prism:number":"5","prism:startingPage":"563","prism:endingPage":"572"},"reviewed":"false","dc:rights":["http://www.nrcresearchpress.com/page/about/CorporateTextAndDataMining"],"url":[{"@id":"https://cdnsciencepub.com/doi/full-xml/10.1139/O07-073"},{"@id":"https://cdnsciencepub.com/doi/pdf/10.1139/O07-073"}],"createdAt":"2007-09-27","modifiedAt":"2025-07-02","relatedProduct":[{"@id":"https://cir.nii.ac.jp/crid/1360290617474636288","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"Oral Bovine Milk Lactoferrin Administration Suppressed Myopia Development through Matrix Metalloproteinase 2 in a Mouse Model"}]}],"dataSourceIdentifier":[{"@type":"CROSSREF","@value":"10.1139/o07-073"},{"@type":"CROSSREF","@value":"10.3390/nu12123744_references_DOI_6ZxwaLQPd9TdPpitRU1CpsAqhWK"}]}