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Inhibition of tubulin deacetylase activity leads to suppression of microtubule dynamics, causing cell cycle arrest and apoptosis, which is a validated strategy for cancer chemotherapy. Selective inhibition of HDAC6 is clinically preferable, since unwanted inhibition of other HDAC isozymes can lead to undesirable off-target effects. Here, X-ray crystal structures of HDAC6-inhibitor complexes reveal molecular features responsible for the isozyme selectivity measured in inhibition assays, including an unusual monodentate hydroxamate-Zn\n                    <jats:sup>2+<\/jats:sup>\n                    coordination mode as well as intermolecular interactions of bulky inhibitor substituents. These observations will inform the design of HDAC6-selective inhibitors with improved properties.\n                  <\/jats:p>","DOI":"10.1073\/pnas.1718823114","type":"journal-article","created":{"date-parts":[[2017,12,4]],"date-time":"2017-12-04T14:55:50Z","timestamp":1512399350000},"page":"13459-13464","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":182,"title":["Unusual zinc-binding mode of HDAC6-selective hydroxamate inhibitors"],"prefix":"10.1073","volume":"114","author":[{"given":"Nicholas J.","family":"Porter","sequence":"first","affiliation":[{"name":"Roy and Diana Vagelos Laboratories, Department of Chemistry, University of Pennsylvania, Philadelphia, PA 19104-6323;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adaickapillai","family":"Mahendran","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Columbia University, New York, NY 10027"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ronald","family":"Breslow","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Columbia University, New York, NY 10027"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David W.","family":"Christianson","sequence":"additional","affiliation":[{"name":"Roy and Diana Vagelos Laboratories, Department of Chemistry, University of Pennsylvania, Philadelphia, PA 19104-6323;"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2017,12,4]]},"reference":[{"key":"e_1_3_4_1_2","doi-asserted-by":"crossref","first-page":"834","DOI":"10.1126\/science.1175371","article-title":"Lysine acetylation targets protein complexes and co-regulates major cellular functions","volume":"325","author":"Choudhary C","year":"2009","unstructured":"C Choudhary, , Lysine acetylation targets protein complexes and co-regulates major cellular functions. 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