{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T15:21:39Z","timestamp":1790263299527,"version":"4.1.0"},"reference-count":44,"publisher":"Wiley","issue":"34","license":[{"start":{"date-parts":[[2024,7,22]],"date-time":"2024-07-22T00:00:00Z","timestamp":1721606400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100010665","name":"H2020 Marie Sk\u0142odowska-Curie Actions","doi-asserted-by":"publisher","award":["956631"],"award-info":[{"award-number":["956631"]}],"id":[{"id":"10.13039\/100010665","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Angew Chem Int Ed"],"published-print":{"date-parts":[[2024,8,19]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    The thiamine diphosphate (ThDP)\u2010binding motif, characterized by the canonical GDG(X)\n                    <jats:sub>24\u201027<\/jats:sub>\n                    N sequence, is highly conserved among ThDP\u2010dependent enzymes. We investigated a ThDP\u2010dependent lyase (JanthE from\n                    <jats:italic>Janthinobacterium sp. HH01<\/jats:italic>\n                    ) with an unusual cysteine (C458) replacing the first glycine of this motif. JanthE exhibits a high substrate promiscuity and accepts long aliphatic\n                    <jats:italic>\u03b1<\/jats:italic>\n                    \u2010keto acids as donors. Sterically hindered aromatic aldehydes or non\u2010activated ketones are acceptor substrates, giving access to a variety of secondary and tertiary alcohols as carboligation products. The crystal structure solved at a resolution of 1.9\u2005\u00c5 reveals that C458 is not primarily involved in cofactor binding as previously thought for the canonical glycine. Instead, it coordinates methionine 406, thus ensuring the integrity of the active site and the enzyme activity. In addition, we have determined the long\u2010sought genuine tetrahedral intermediates formed with pyruvate and 2\u2010oxobutyrate in the pre\u2010decarboxylation states and deciphered the atomic details for their stabilization in the active site. Collectively, we unravel an unexpected role for the first residue of the ThDP\u2010binding motif and unlock a family of lyases that can perform valuable carboligation reactions.\n                  <\/jats:p>","DOI":"10.1002\/anie.202404045","type":"journal-article","created":{"date-parts":[[2024,6,14]],"date-time":"2024-06-14T07:06:14Z","timestamp":1718348774000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Identification and Characterization of Thiamine Diphosphate\u2010Dependent Lyases with an Unusual CDG Motif"],"prefix":"10.1002","volume":"63","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-9294-2932","authenticated-orcid":false,"given":"Lucrezia","family":"Lanza","sequence":"first","affiliation":[{"name":"Institute of Pharmaceutical Sciences Albert-Ludwigs-Universit\u00e4t Freiburg  Albertstrasse 25 79104 Freiburg im Breisgau Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3925-8127","authenticated-orcid":false,"given":"Fabian","family":"Rabe von Pappenheim","sequence":"additional","affiliation":[{"name":"Department of Molecular Enzymology Georg-August Universit\u00e4t G\u00f6ttingen Max-Planck-Institute for Multidisciplinary Sciences  G\u00f6ttingen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-7518-1880","authenticated-orcid":false,"given":"Daniela","family":"Bjarnesen","sequence":"additional","affiliation":[{"name":"Institute of Pharmaceutical Sciences Albert-Ludwigs-Universit\u00e4t Freiburg  Albertstrasse 25 79104 Freiburg im Breisgau Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5462-9491","authenticated-orcid":false,"given":"Camilla","family":"Leogrande","sequence":"additional","affiliation":[{"name":"Department of Molecular Enzymology Georg-August Universit\u00e4t G\u00f6ttingen Max-Planck-Institute for Multidisciplinary Sciences  G\u00f6ttingen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra","family":"Paul","sequence":"additional","affiliation":[{"name":"Institute of Pharmaceutical Sciences Albert-Ludwigs-Universit\u00e4t Freiburg  Albertstrasse 25 79104 Freiburg im Breisgau Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-7166-1490","authenticated-orcid":false,"given":"Leonhard","family":"Krug","sequence":"additional","affiliation":[{"name":"Institute of Pharmaceutical Sciences Albert-Ludwigs-Universit\u00e4t Freiburg  Albertstrasse 25 79104 Freiburg im Breisgau Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7891-7108","authenticated-orcid":false,"given":"Kai","family":"Tittmann","sequence":"additional","affiliation":[{"name":"Department of Molecular Enzymology Georg-August Universit\u00e4t G\u00f6ttingen Max-Planck-Institute for Multidisciplinary Sciences  G\u00f6ttingen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2742-4992","authenticated-orcid":false,"given":"Michael","family":"M\u00fcller","sequence":"additional","affiliation":[{"name":"Institute of Pharmaceutical Sciences Albert-Ludwigs-Universit\u00e4t Freiburg  Albertstrasse 25 79104 Freiburg im Breisgau Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,7,22]]},"reference":[{"key":"e_1_2_8_1_1","doi-asserted-by":"crossref","unstructured":"Chikunova M. 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