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Here we describe several structural states of the protein by X-ray crystallography and further characterize them by molecular dynamics simulations. The transition between these conformers is triggered by substrate binding and calcium ligation, respectively, and helps explain the stringent specificity of furin and its functional features. These studies may pave the way for novel strategies of structure-guided inhibitor development.<\/jats:p>","DOI":"10.1073\/pnas.1613630113","type":"journal-article","created":{"date-parts":[[2016,9,19]],"date-time":"2016-09-19T22:39:56Z","timestamp":1474324796000},"page":"11196-11201","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":79,"title":["Structure of the unliganded form of the proprotein convertase furin suggests activation by a substrate-induced mechanism"],"prefix":"10.1073","volume":"113","author":[{"given":"Sven O.","family":"Dahms","sequence":"first","affiliation":[{"name":"Protein Crystallography Group, Leibniz Institute on Aging\u2013Fritz Lipmann Institute (FLI), 07745 Jena, Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcelino","family":"Arciniega","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Structural Biology, Institute of Cellular Physiology, Universidad Nacional Aut\u00f3noma de M\u00e9xico, 04510 Mexico City, Mexico;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Torsten","family":"Steinmetzer","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, Philipps University Marburg, D-35032 Marburg, Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Huber","sequence":"additional","affiliation":[{"name":"Emeritus Group Structure Research, Max Planck Institut f\u00fcr Biochemie, 82152 Martinsried, Germany;"},{"name":"Emeritus of Excellence Technische Universit\u00e4t M\u00fcnchen, 85748 Garching, Germany;"},{"name":"Zentrum f\u00fcr Medizinische Biotechnologie, Universit\u00e4t Duisburg-Essen, 45117 Essen, Germany;"},{"name":"School of Biosciences, Cardiff University, Cardiff CF10 3US, Wales, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manuel E.","family":"Than","sequence":"additional","affiliation":[{"name":"Protein Crystallography Group, Leibniz Institute on Aging\u2013Fritz Lipmann Institute (FLI), 07745 Jena, Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2016,9,19]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"crossref","first-page":"753","DOI":"10.1038\/nrm934","article-title":"Furin at the cutting edge: From protein traffic to embryogenesis and disease","volume":"3","author":"Thomas G","year":"2002","unstructured":"G Thomas, Furin at the cutting edge: From protein traffic to embryogenesis and disease. 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