{"id":{"repo_id":"missouri","oai_identifier":"oai:mospace.umsystem.edu:10355/49038"},"canonical_url":"https://search.dev.ndltd.org/etd/missouri/oai:mospace.umsystem.edu:10355/49038","repository":{"repo_id":"missouri","name":"University of Missouri","base_url":"https://mospace.umsystem.edu/oai/request"},"display":{"title":"Transient collagen triple-helix binding to membrane type 1 matrix metalloproteinase : interaction studies and NMR-guided structural docking","abstract":"[ACCESS RESTRICTED TO THE UNIVERSITY OF MISSOURI AT AUTHOR'S REQUEST.] MT1-MMP (MMP-14) as pericellular collagenase is critically involved in cancer cell invasion through collagen barriers that it degrades. To better understand the structural and mechanistic details underlying collagenolytic activity of MMP-14, a solution NMR approach is used here to investigate interactions between individual MMP-14 catalytic and hemopexin domain and a collagen-I-mimicking Triple-Helical Peptide (THP). In this study, backbone chemical shifts were assigned for isolated MMP-14 catalytic and hemopexin domains. The results from gel-filtration chromatography, DLS and NMR combined suggested that MMP-14 hemopexin domain behaves consistently as a monomer in solution. NMR-monitored THP titration led to identification of a distinct patch centered about blade I at the exit side of the hemopexin domain as a potential THP binding exosite. Mutation of residues from this area impairs triple-helical peptidase activity of MMP-14. Saturation transfer difference NMR suggests rotational averaging around the longitudinal axis of the triple-helical peptide. Additionally, intermolecular distances between the hemopexin domain of MMP-14 (HPX-14) and THP were measured by paramagnetic NMR using TOAC-labeled THP. Structural models of HPX-14/THP calculated based on PRE-measured distance restraints revealed extensive interaction between MMP-14 hemopexin domain and sequences surrounding the cleavage site in the THP, indicating a distinctive arrangement of the catalytic domain and unique collagen binding conformation of MMP-14 during collagenolysis.","abstract_html":"[ACCESS RESTRICTED TO THE UNIVERSITY OF MISSOURI AT AUTHOR'S REQUEST.] MT1-MMP (MMP-14) as pericellular collagenase is critically involved in cancer cell invasion through collagen barriers that it degrades. To better understand the structural and mechanistic details underlying collagenolytic activity of MMP-14, a solution NMR approach is used here to investigate interactions between individual MMP-14 catalytic and hemopexin domain and a collagen-I-mimicking Triple-Helical Peptide (THP). In this study, backbone chemical shifts were assigned for isolated MMP-14 catalytic and hemopexin domains. The results from gel-filtration chromatography, DLS and NMR combined suggested that MMP-14 hemopexin domain behaves consistently as a monomer in solution. NMR-monitored THP titration led to identification of a distinct patch centered about blade I at the exit side of the hemopexin domain as a potential THP binding exosite. Mutation of residues from this area impairs triple-helical peptidase activity of MMP-14. Saturation transfer difference NMR suggests rotational averaging around the longitudinal axis of the triple-helical peptide. Additionally, intermolecular distances between the hemopexin domain of MMP-14 (HPX-14) and THP were measured by paramagnetic NMR using TOAC-labeled THP. Structural models of HPX-14/THP calculated based on PRE-measured distance restraints revealed extensive interaction between MMP-14 hemopexin domain and sequences surrounding the cleavage site in the THP, indicating a distinctive arrangement of the catalytic domain and unique collagen binding conformation of MMP-14 during collagenolysis.","abstract_has_math":false,"creators":["Zhao, Yingchu"],"institution":"University of Missouri--Columbia","degree_name":"Ph. D.","degree_level":"Doctoral","degree_discipline":"Biochemistry (MU)","degree_department":null,"school":null,"contributors":[],"advisors":["Van Doren, Steven R., 1963-"],"committee_chairs":[],"committee_members":[],"year":2015,"date_issued":"2015","date_published":"2015","updated_at":"2026-07-24T03:09:05Z","subjects":[],"languages":["eng","English"],"rights":["Access to files is limited to the campuses of the University of Missouri with SSO login."],"rights_urls":[],"identifier_entries":[{"key":"dc:identifier.doi","label":"DOI","values":["https://doi.org/10.32469/10355/49038"],"render_values":[{"text":"https://doi.org/10.32469/10355/49038","href":"https://doi.org/10.32469/10355/49038","code":true}]}]},"links":{"outbound_url":"https://hdl.handle.net/10355/49038","outbound_label":"Handle","outbound_source":"dc:identifier.uri"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor.advisor","label":"Advisor","values":["Van Doren, Steven R., 1963-"]},{"key":"dc:creator","label":"Author","values":["Zhao, Yingchu"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date.accessioned","label":"Dc Date Accessioned","values":["2016-05-06T16:38:21Z"]},{"key":"dc:date.available","label":"Dc Date Available","values":["2016-05-06T16:38:21Z"]},{"key":"dc:date.issued","label":"Date","values":["2015"]},{"key":"dc:publisher","label":"Institution","values":["University of Missouri--Columbia"]},{"key":"dc:type","label":"Dc Type","values":["Thesis"]},{"key":"thesis:degree_discipline","label":"Discipline","values":["Biochemistry (MU)"]},{"key":"thesis:degree_level","label":"Degree Level","values":["Doctoral"]},{"key":"thesis:degree_name","label":"Degree Name","values":["Ph. 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To better understand the structural and mechanistic details underlying collagenolytic activity of MMP-14, a solution NMR approach is used here to investigate interactions between individual MMP-14 catalytic and hemopexin domain and a collagen-I-mimicking Triple-Helical Peptide (THP). In this study, backbone chemical shifts were assigned for isolated MMP-14 catalytic and hemopexin domains. The results from gel-filtration chromatography, DLS and NMR combined suggested that MMP-14 hemopexin domain behaves consistently as a monomer in solution. NMR-monitored THP titration led to identification of a distinct patch centered about blade I at the exit side of the hemopexin domain as a potential THP binding exosite. Mutation of residues from this area impairs triple-helical peptidase activity of MMP-14. Saturation transfer difference NMR suggests rotational averaging around the longitudinal axis of the triple-helical peptide. Additionally, intermolecular distances between the hemopexin domain of MMP-14 (HPX-14) and THP were measured by paramagnetic NMR using TOAC-labeled THP. Structural models of HPX-14/THP calculated based on PRE-measured distance restraints revealed extensive interaction between MMP-14 hemopexin domain and sequences surrounding the cleavage site in the THP, indicating a distinctive arrangement of the catalytic domain and unique collagen binding conformation of MMP-14 during collagenolysis."]},{"key":"dc:title","label":"Title","values":["Transient collagen triple-helix binding to membrane type 1 matrix metalloproteinase : interaction studies and NMR-guided structural docking"]}]}],"canonical_facts":{"dc:contributor.advisor":["Van Doren, Steven R., 1963-"],"dc:creator":["Zhao, Yingchu"],"dc:date.accessioned":["2016-05-06T16:38:21Z"],"dc:date.available":["2016-05-06T16:38:21Z"],"dc:date.issued":["2015"],"dc:description.abstract":["[ACCESS RESTRICTED TO THE UNIVERSITY OF MISSOURI AT AUTHOR'S REQUEST.] MT1-MMP (MMP-14) as pericellular collagenase is critically involved in cancer cell invasion through collagen barriers that it degrades. To better understand the structural and mechanistic details underlying collagenolytic activity of MMP-14, a solution NMR approach is used here to investigate interactions between individual MMP-14 catalytic and hemopexin domain and a collagen-I-mimicking Triple-Helical Peptide (THP). In this study, backbone chemical shifts were assigned for isolated MMP-14 catalytic and hemopexin domains. The results from gel-filtration chromatography, DLS and NMR combined suggested that MMP-14 hemopexin domain behaves consistently as a monomer in solution. NMR-monitored THP titration led to identification of a distinct patch centered about blade I at the exit side of the hemopexin domain as a potential THP binding exosite. Mutation of residues from this area impairs triple-helical peptidase activity of MMP-14. Saturation transfer difference NMR suggests rotational averaging around the longitudinal axis of the triple-helical peptide. Additionally, intermolecular distances between the hemopexin domain of MMP-14 (HPX-14) and THP were measured by paramagnetic NMR using TOAC-labeled THP. Structural models of HPX-14/THP calculated based on PRE-measured distance restraints revealed extensive interaction between MMP-14 hemopexin domain and sequences surrounding the cleavage site in the THP, indicating a distinctive arrangement of the catalytic domain and unique collagen binding conformation of MMP-14 during collagenolysis."],"dc:identifier.doi":["https://doi.org/10.32469/10355/49038"],"dc:identifier.uri":["https://hdl.handle.net/10355/49038"],"dc:language":["English"],"dc:language.iso":["eng"],"dc:publisher":["University of Missouri--Columbia"],"dc:rights":["Access to files is limited to the campuses of the University of Missouri with SSO login."],"dc:title":["Transient collagen triple-helix binding to membrane type 1 matrix metalloproteinase : interaction studies and NMR-guided structural docking"],"dc:type":["Thesis"],"thesis:degree_discipline":["Biochemistry (MU)"],"thesis:degree_level":["Doctoral"],"thesis:degree_name":["Ph. D."],"thesis:institution_name":["University of Missouri--Columbia"]},"updated_at":"2026-07-24T03:09:05Z"}