{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T09:14:32Z","timestamp":1788340472418,"version":"build-2803163510"},"reference-count":40,"publisher":"International Union of Crystallography (IUCr)","issue":"9","license":[{"start":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T00:00:00Z","timestamp":1787788800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/legalcode"},{"start":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T00:00:00Z","timestamp":1787788800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/legalcode"}],"content-domain":{"domain":["iucr.org","wiley.com","iucrj.org"],"crossmark-restriction":true},"short-container-title":["Acta Crystallogr D Struct Biol","Acta Crystallogr D","Acta Cryst D","Acta Cryst D Struct Biol","Acta Cryst Sect D","Acta Cryst Sect D Struct Biol","Acta Crystallogr Sect D","Acta Crystallogr Sect D Struct Biol","Acta Crystallogr D Biol Crystallogr","Acta Cryst D Biol Cryst"],"accepted":{"date-parts":[[2026,8,18]]},"published-print":{"date-parts":[[2026,9,1]]},"abstract":"<jats:p>\n                    The histone lysine acetyltransferase KAT6A belongs to the MYST family of lysine acetyltransferases which consists of five isoforms. KAT6A (and its paralog KAT6B) have emerged as a promising epigenetic drug targets in cancer, supported by recent clinical data. As support for our high-throughput screening approach aimed at discovering new inhibitors of KAT6A, we developed a crystallization platform system termed KAT6A\n                    <jats:sup>mutCys<\/jats:sup>\n                    in which four surface cysteine residues of KAT6A were mutated to serine. This construct crystallizes readily when in complex with its cofactor AcCoA. The obtained co-crystals were successfully used in a back-soaking approach in which AcCoA was soaked out of the crystals and small-molecule inhibitors were soaked in. In parallel, we explored a previously published surrogate approach termed MYST\n                    <jats:sup>cryst<\/jats:sup>\n                    in which active-site residues of the related, but easier to crystallize, enzyme KAT8 were mutated to those found in KAT6A. By comparing co-crystal structures of the same ligand bound to KAT6A from our Cys-to-Ser approach and to mutated KAT8 (MYST\n                    <jats:sup>cryst<\/jats:sup>\n                    ) we found that the KAT8 surrogate approach indeed successfully reproduced the binding mode observed in the KAT6A structure, while delivering structures with significantly higher resolution. The MYST\n                    <jats:sup>cryst<\/jats:sup>\n                    approach was therefore employed to determine the binding modes of two further small-molecule inhibitors, both from our KAT6A inhibitor optimization program and from a competitor lead series. These structures reveal alternative inhibitor conformations at the binding-site entry and the importance of filling a hydrophobic subpocket in the interior of the binding pocket. These insights will aid future efforts towards the development of KAT6A inhibitors as anticancer drugs.\n                  <\/jats:p>","DOI":"10.1107\/s2059798326008545","type":"journal-article","created":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T15:14:40Z","timestamp":1787325280000},"page":"1111-1124","update-policy":"https:\/\/doi.org\/10.1107\/cm_01","source":"Crossref","is-referenced-by-count":0,"title":["KAT6A\u2013inhibitor co-crystal structures: tackling a challenging crystallization target via two alternative approaches"],"prefix":"10.1107","volume":"82","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9065-1322","authenticated-orcid":true,"given":"Vera","family":"Puetter","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8523-812X","authenticated-orcid":true,"given":"L\u00e9a","family":"Bouch\u00e9","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katrin","family":"Nowak-Reppel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-8275-2321","authenticated-orcid":true,"given":"Steven J.","family":"Ferrara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7728-1192","authenticated-orcid":true,"given":"Stefan N.","family":"Gradl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6250-6344","authenticated-orcid":true,"given":"Daniel","family":"Korr","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Craig A.","family":"Strathdee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1820-002X","authenticated-orcid":true,"given":"Antonius","family":"ter Laak","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6267-7250","authenticated-orcid":true,"given":"Roman C.","family":"Hillig","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"329","published-online":{"date-parts":[[2026,8,27]]},"reference":[{"key":"ud5061_bb1","doi-asserted-by":"crossref","first-page":"384","DOI":"10.1038\/nrd3674","volume":"11","author":"Arrowsmith","year":"2012","journal-title":"Nat. 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