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The structure suggests a strategy for the design of inhibitors that target specific splice variants of this enzyme. By mapping onto our structure all the mutations in PDE4D that underlie the rare human genetic disorder of acrodysostosis, we present a rationale for why they could lead to a dysregulation of PDE4D activity.<\/jats:p>","DOI":"10.1073\/pnas.1419906112","type":"journal-article","created":{"date-parts":[[2015,3,9]],"date-time":"2015-03-09T22:42:15Z","timestamp":1425940935000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":76,"title":["Engineered stabilization and structural analysis of the autoinhibited conformation of PDE4"],"prefix":"10.1073","volume":"112","author":[{"given":"Peder","family":"Cedervall","sequence":"first","affiliation":[{"name":"Structural Biology and Biophysics Group, Worldwide Research and Development, Pfizer, Inc., Groton, CT 06340"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ann","family":"Aulabaugh","sequence":"additional","affiliation":[{"name":"Structural Biology and Biophysics Group, Worldwide Research and Development, Pfizer, Inc., Groton, CT 06340"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kieran F.","family":"Geoghegan","sequence":"additional","affiliation":[{"name":"Structural Biology and Biophysics Group, Worldwide Research and Development, Pfizer, Inc., Groton, CT 06340"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas J.","family":"McLellan","sequence":"additional","affiliation":[{"name":"Structural Biology and Biophysics Group, Worldwide Research and Development, Pfizer, Inc., Groton, CT 06340"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6128-7779","authenticated-orcid":false,"given":"Jayvardhan","family":"Pandit","sequence":"additional","affiliation":[{"name":"Structural Biology and Biophysics Group, Worldwide Research and Development, Pfizer, Inc., Groton, CT 06340"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2015,3,9]]},"reference":[{"key":"e_1_3_4_1_2","doi-asserted-by":"crossref","first-page":"710","DOI":"10.1038\/nrm911","article-title":"Cyclic nucleotide research\u2014Still expanding after half a century","volume":"3","author":"Beavo JA","year":"2002","unstructured":"JA Beavo, LL Brunton, Cyclic nucleotide research\u2014Still expanding after half a century. 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