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It is an important factor in epigenetic regulation and more generally in the posttranslational regulation of protein stability, association and activity. Some of these enzymes can also cleave off fatty acids or dicarboxylic acids from lysines in proteins. The NAD\n                    <jats:sup>+<\/jats:sup>\n                    \u2010dependent deacetylases are termed Sirtuins and are implicated in the pathogenesis of different diseases. For the isotype Sirt2 highly selective inhibitors have been identified in the last few years. Many of those Sirt2 selective compounds, like the Sirtuin rearranging ligands (SirReals) discovered in our group, have been shown or are postulated to bind to the so\u2010called selectivity pocket. This binding site is not observed in crystal structures of the apo\u2010enzyme but can be opened up by long chain fatty acid substrates respectively suitable inhibitors. Recently, this unique feature of Sirt2 was exploited to provide highly potent and selective tools for the chemical biology of Sirtuins. Here, we shortly review Sirtuin biology, present inhibitors that have either been confirmed or postulated to bind to the selectivity pocket, their applications and an outlook regarding mechanistic investigations.\n                  <\/jats:p>","DOI":"10.1002\/tcr.201800044","type":"journal-article","created":{"date-parts":[[2018,6,22]],"date-time":"2018-06-22T02:30:42Z","timestamp":1529634642000},"page":"1701-1707","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Opening the Selectivity Pocket in the Human Lysine Deacetylase Sirtuin2 \u2013 New Opportunities, New Questions"],"prefix":"10.1002","volume":"18","author":[{"given":"Dina","family":"Robaa","sequence":"first","affiliation":[{"name":"Institute of Pharmacy Martin-Luther-University Halle-Wittenberg  Wolfgang-Langenbeck-Str. 4 06120 Halle (Saale) Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daria","family":"Monaldi","sequence":"additional","affiliation":[{"name":"Institute of Pharmaceutical Sciences University of Freiburg  Albertstr. 25 79104 Freiburg Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nathalie","family":"W\u00f6ssner","sequence":"additional","affiliation":[{"name":"Institute of Pharmaceutical Sciences University of Freiburg  Albertstr. 25 79104 Freiburg Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Norio","family":"Kudo","sequence":"additional","affiliation":[{"name":"RIKEN Center for Sustainable Resource Science  Hirosawa 2\u20131, Wako Saitama 351-0198 Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tobias","family":"Rumpf","sequence":"additional","affiliation":[{"name":"Department of Chromatin Regulation Max Planck Institute of Immunobiology and Epigenetics  St\u00fcbeweg 51 79108 Freiburg Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matthias","family":"Schiedel","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Chemistry Research Laboratory University of Oxford  Mansfield Road OX1 3TA Oxford United Kingdom."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Minoru","family":"Yoshida","sequence":"additional","affiliation":[{"name":"RIKEN Center for Sustainable Resource Science  Hirosawa 2\u20131, Wako Saitama 351-0198 Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6361-7716","authenticated-orcid":false,"given":"Manfred","family":"Jung","sequence":"additional","affiliation":[{"name":"Institute of Pharmaceutical Sciences University of Freiburg  Albertstr. 25 79104 Freiburg Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2018,6,21]]},"reference":[{"key":"e_1_2_5_1_1","doi-asserted-by":"publisher","DOI":"10.1002\/wsbm.1185"},{"key":"e_1_2_5_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrm3931"},{"key":"e_1_2_5_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrm3841"},{"key":"e_1_2_5_4_1","unstructured":"\u00a0"},{"key":"e_1_2_5_5_2","doi-asserted-by":"publisher","DOI":"10.1021\/cb500848p"},{"key":"e_1_2_5_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2017.02.018"},{"key":"e_1_2_5_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)81063-6"},{"key":"e_1_2_5_8_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.272.5260.408"},{"key":"e_1_2_5_9_1","unstructured":"\u00a0"},{"key":"e_1_2_5_10_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms18071414"},{"key":"e_1_2_5_11_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13045-016-0267-0"},{"key":"e_1_2_5_12_1","unstructured":"\u00a0"},{"key":"e_1_2_5_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)41547-5"},{"key":"e_1_2_5_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(17)44885-X"},{"key":"e_1_2_5_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0960-894X(97)00284-9"},{"key":"e_1_2_5_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbapap.2010.01.021"},{"key":"e_1_2_5_17_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.R112.378877"},{"key":"e_1_2_5_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbapap.2009.09.009"},{"key":"e_1_2_5_19_1","unstructured":"\u00a0"},{"key":"e_1_2_5_20_2","doi-asserted-by":"publisher","DOI":"10.1158\/1541-7786.MCR-13-0040-T"},{"key":"e_1_2_5_21_2","doi-asserted-by":"publisher","DOI":"10.1038\/cdd.2012.147"},{"key":"e_1_2_5_22_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0002428"},{"key":"e_1_2_5_23_2","first-page":"371","volume":"9","author":"Elliott P. 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