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U.S.A."],"published-print":{"date-parts":[[2018,12,26]]},"abstract":"<jats:p>HIV-1 protease (PR) cleavage of the Gag polyprotein triggers the assembly of mature, infectious particles. Final cleavage of Gag occurs at the junction helix between the capsid protein CA and the SP1 spacer peptide. Here we used MicroED to delineate the binding interactions of the maturation inhibitor bevirimat (BVM) using very thin frozen-hydrated, 3D microcrystals of a CTD-SP1 Gag construct with and without bound BVM. The 2.9-\u00c5 MicroED structure revealed that a single BVM molecule stabilizes the six-helix bundle via both electrostatic interactions with the dimethylsuccinyl moiety and hydrophobic interactions with the pentacyclic triterpenoid ring. These results provide insight into the mechanism of action of BVM and related maturation inhibitors that will inform further drug discovery efforts. This study also demonstrates the capabilities of MicroED for structure-based drug design.<\/jats:p>","DOI":"10.1073\/pnas.1806806115","type":"journal-article","created":{"date-parts":[[2018,12,10]],"date-time":"2018-12-10T20:16:38Z","timestamp":1544472998000},"page":"13258-13263","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":97,"title":["MicroED structures of HIV-1 Gag CTD-SP1 reveal binding interactions with the maturation inhibitor bevirimat"],"prefix":"10.1073","volume":"115","author":[{"given":"Michael D.","family":"Purdy","sequence":"first","affiliation":[{"name":"Department of Molecular Physiology and Biological Physics, University of Virginia School of Medicine, Charlottesville, VA 22908;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dan","family":"Shi","sequence":"additional","affiliation":[{"name":"Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA 20147;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jakub","family":"Chrustowicz","sequence":"additional","affiliation":[{"name":"Department of Molecular Physiology and Biological Physics, University of Virginia School of Medicine, Charlottesville, VA 22908;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8936-0912","authenticated-orcid":false,"given":"Johan","family":"Hattne","sequence":"additional","affiliation":[{"name":"Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA 20147;"},{"name":"Howard Hughes Medical Institute, Los Angeles, CA 90095;"},{"name":"Department of Biological Chemistry, University of California, Los Angeles, Los Angeles CA 90095;"},{"name":"Department of Physiology, University of California, Los Angeles, Los Angeles CA 90095;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tamir","family":"Gonen","sequence":"additional","affiliation":[{"name":"Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA 20147;"},{"name":"Howard Hughes Medical Institute, Los Angeles, CA 90095;"},{"name":"Department of Biological Chemistry, University of California, Los Angeles, Los Angeles CA 90095;"},{"name":"Department of Physiology, University of California, Los Angeles, Los Angeles CA 90095;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Yeager","sequence":"additional","affiliation":[{"name":"Department of Molecular Physiology and Biological Physics, University of Virginia School of Medicine, Charlottesville, VA 22908;"},{"name":"Department of Medicine, University of Virginia School of Medicine, Charlottesville, VA 22908;"},{"name":"Center for Membrane and Cell Physiology, University of Virginia School of Medicine, Charlottesville, VA 22908;"},{"name":"Cardiovascular Research Center, University of Virginia School of Medicine, Charlottesville, VA 22908"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2018,12,10]]},"reference":[{"key":"e_1_3_4_1_2","doi-asserted-by":"crossref","first-page":"a006924","DOI":"10.1101\/cshperspect.a006924","article-title":"HIV-1 assembly, budding, and maturation","volume":"2","author":"Sundquist WI","year":"2012","unstructured":"WI Sundquist, HG Kr\u00e4usslich, HIV-1 assembly, budding, and maturation. 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