{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,8]],"date-time":"2025-10-08T22:22:43Z","timestamp":1759962163509,"version":"3.41.2"},"reference-count":39,"publisher":"Wiley","issue":"49","license":[{"start":{"date-parts":[[2022,11,9]],"date-time":"2022-11-09T00:00:00Z","timestamp":1667952000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Angew Chem Int Ed"],"published-print":{"date-parts":[[2022,12,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Regulation of enzyme activity is vital for living organisms. In metalloenzymes, far\u2010reaching rearrangements of the protein scaffold are generally required to tune the metal cofactor's properties by allosteric regulation. Here structural analysis of hydroxyketoacid aldolase from <jats:italic>Sphingomonas wittichii<\/jats:italic> RW1 (<jats:italic>Sw<\/jats:italic>HKA) revealed a dynamic movement of the metal cofactor between two coordination spheres without protein scaffold rearrangements. In its resting state configuration (M<jats:sup>2+<\/jats:sup><jats:sub>R<\/jats:sub>), the metal constitutes an integral part of the dimer interface within the overall hexameric assembly, but sterical constraints do not allow for substrate binding. Conversely, a second coordination sphere constitutes the catalytically active state (M<jats:sup>2+<\/jats:sup><jats:sub>A<\/jats:sub>) at 2.4\u2005\u00c5 distance. Bidentate coordination of a ketoacid substrate to M<jats:sup>2+<\/jats:sup><jats:sub>A<\/jats:sub> affords the overall lowest energy complex, which drives the transition from M<jats:sup>2+<\/jats:sup><jats:sub>R<\/jats:sub> to M<jats:sup>2+<\/jats:sup><jats:sub>A<\/jats:sub>. While not described earlier, this type of regulation may be widespread and largely overlooked due to low occupancy of some of its states in protein crystal structures.<\/jats:p>","DOI":"10.1002\/anie.202213338","type":"journal-article","created":{"date-parts":[[2022,10,10]],"date-time":"2022-10-10T14:50:32Z","timestamp":1665413432000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Substrate Induced Movement of the Metal Cofactor between Active and Resting State"],"prefix":"10.1002","volume":"61","author":[{"given":"Stefan R.","family":"Marsden","sequence":"first","affiliation":[{"name":"Biokatalyse, Afdeling Biotechnologie Technische Universiteit Delft  van der Maasweg 9 2629HZ Delft The Netherlands"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0891-6972","authenticated-orcid":false,"given":"Hein J.","family":"Wijma","sequence":"additional","affiliation":[{"name":"Groningen Biomolecular Sciences and Biotechnology Institute Faculty of Science and Engineering University of Groningen  Nijenborg 4 9747AG Groningen The Netherlands"}]},{"given":"Michael K. F.","family":"Mohr","sequence":"additional","affiliation":[{"name":"Biokatalyse, Afdeling Biotechnologie Technische Universiteit Delft  van der Maasweg 9 2629HZ Delft The Netherlands"}]},{"given":"In\u00eas","family":"Justo","sequence":"additional","affiliation":[{"name":"EMBL Hamburg  Notkestrasse 85 22607 Hamburg Germany"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6342-2022","authenticated-orcid":false,"given":"Peter\u2010Leon","family":"Hagedoorn","sequence":"additional","affiliation":[{"name":"Biokatalyse, Afdeling Biotechnologie Technische Universiteit Delft  van der Maasweg 9 2629HZ Delft The Netherlands"}]},{"given":"Jesper","family":"Laustsen","sequence":"additional","affiliation":[{"name":"EMBL Hamburg  Notkestrasse 85 22607 Hamburg Germany"}]},{"given":"Cy M.","family":"Jeffries","sequence":"additional","affiliation":[{"name":"EMBL Hamburg  Notkestrasse 85 22607 Hamburg Germany"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0830-5696","authenticated-orcid":false,"given":"Dmitri","family":"Svergun","sequence":"additional","affiliation":[{"name":"EMBL Hamburg  Notkestrasse 85 22607 Hamburg Germany"}]},{"given":"Luuk","family":"Mestrom","sequence":"additional","affiliation":[{"name":"Biokatalyse, Afdeling Biotechnologie Technische Universiteit Delft  van der Maasweg 9 2629HZ Delft The Netherlands"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6614-4494","authenticated-orcid":false,"given":"Duncan G. 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