{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,29]],"date-time":"2026-08-29T06:17:00Z","timestamp":1787984220881,"version":"build-2784847793"},"reference-count":46,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T00:00:00Z","timestamp":1787875200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T00:00:00Z","timestamp":1787875200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001711","name":"Schweizerischer Nationalfonds zur F\u00f6rderung der Wissenschaftlichen Forschung","doi-asserted-by":"publisher","award":["TMAG\u20102_209202"],"award-info":[{"award-number":["TMAG\u20102_209202"]}],"id":[{"id":"10.13039\/501100001711","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Angew Chem Int Ed"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Collagen cross\u2010linking is essential for the structural integrity of the extracellular matrix. In several pathological conditions, the triple\u2010helical core of collagen is disrupted, and proline\u2010rich single strands occur. Lysyl oxidases (LOXs), enzymes that initiate cross\u2010linking by catalyzing the oxidative deamination of lysine to allysine residues, are upregulated in disease. Surprisingly little is known about the selectivity of LOXs. LOX\u2010initiated cross\u2010linking is believed to occur exclusively in the unstructured terminal domains of collagen, the telopeptides. But is this really the case? Herein, we show, with a combination of tailored chemical probes, enzymatic assays, CD and NMR spectroscopic analyses, that LOXL2 oxidizes Lys in proline\u2010rich single strands but not in triple helices. A comparison of Lys\u2010containing collagen model peptides (CMPs) with Lys\u2010containing telopeptides revealed comparable or higher oxidation rates in proline\u2010rich segments. The data suggest that LOXL2\u2010initiated cross\u2010linking occurs in pathologically disrupted triple\u2010helical domains, offering insights into aberrant extracellular matrix stiffening.<\/jats:p>","DOI":"10.1002\/anie.1329257","type":"journal-article","created":{"date-parts":[[2026,8,29]],"date-time":"2026-08-29T05:38:31Z","timestamp":1787981911000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Lysine Oxidation by LOXL2 in Single Strands Versus Triple Helices: Implications for Collagen\u2010Related Diseases"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7385-0071","authenticated-orcid":false,"given":"Laura M.","family":"Poller","sequence":"first","affiliation":[{"name":"Laboratory of Organic Chemistry ETH Z\u00fcrich  Z\u00fcrich Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6949-4561","authenticated-orcid":false,"given":"Tomas","family":"Fiala","sequence":"additional","affiliation":[{"name":"Laboratory of Organic Chemistry ETH Z\u00fcrich  Z\u00fcrich Switzerland"},{"name":"Department of Chemistry, Faculty of Science Masaryk University  Brno Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3075-5741","authenticated-orcid":false,"given":"Helma","family":"Wennemers","sequence":"additional","affiliation":[{"name":"Laboratory of Organic Chemistry ETH Z\u00fcrich  Z\u00fcrich Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,8,28]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.biochem.77.032207.120833"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a004978"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598\u2010023\u201031566\u2010z"},{"key":"e_1_2_8_5_1","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1042\/bse0520113","article-title":"Lysine Post\u2010translational Modifications of Collagen","volume":"52","author":"Yamauchi M.","year":"2012","journal-title":"Essays in Biochemistry"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.273.5278.1078"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021\u20109258(18)67681\u20101"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00018\u2010006\u20106149\u20109"},{"key":"e_1_2_8_9_1","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1042\/EBC20180050","article-title":"Lysyl Oxidases: From Enzyme Activity to Extracellular Matrix Cross\u2010Links","volume":"63","author":"Vallet S. 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Q = glutamine Gln; E = glutamic acid Glu; A = alanine Ala; H = histidine His."},{"key":"e_1_2_8_31_1","unstructured":"\u201cUniProt\u2014P02452 CO1A1_HUMAN \u201d can be found underhttps:\/\/www.uniprot.org\/uniprotkb\/P02452\/entry#sequences(accessed 30 July2025)."},{"key":"e_1_2_8_32_1","unstructured":"\u201cUniProt\u2014P02461 CO3A1_HUMAN \u201d can be found underhttps:\/\/www.uniprot.org\/uniprotkb\/P02461\/entry#sequences(accessed 30 July2025)."},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1021\/ja005542v"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1021\/ja061793d"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1002\/1521\u20103773(20010302)40:5<923::AID\u2010ANIE923>3.0.CO;2\u2010"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1021\/ja103392t"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.2c08727"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.biomac.3c00241"},{"key":"e_1_2_8_39_1","unstructured":"Triple helices arising from the assembly of analogous 21\u2010mer CMPs haveTmvalues of 38.3\u00b0C (21\u2010X) and 40.3\u00b0C (21\u2010Y) (Table S1)."},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1006\/abio.2001.5464"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.biochem.5c00787"},{"key":"e_1_2_8_42_1","unstructured":"Of note the relative activity of LOXL2 is likely maintained at the extracellular pH value of pH 7.4."},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cbpa.2019.02.021"},{"key":"e_1_2_8_44_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41589\u2010021\u201000830\u20106"},{"key":"e_1_2_8_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.matbio.2024.02.006"},{"key":"e_1_2_8_46_1","doi-asserted-by":"publisher","DOI":"10.1002\/bip.1977.360160310"},{"key":"e_1_2_8_47_1","doi-asserted-by":"publisher","DOI":"10.1006\/jmbi.2001.4644"}],"container-title":["Angewandte Chemie International Edition"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/anie.1329257","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/anie.1329257","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/anie.1329257","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,29]],"date-time":"2026-08-29T05:38:34Z","timestamp":1787981914000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/anie.1329257"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,28]]},"references-count":46,"alternative-id":["10.1002\/anie.1329257"],"URL":"https:\/\/doi.org\/10.1002\/anie.1329257","archive":["Portico"],"relation":{},"ISSN":["1433-7851","1521-3773"],"issn-type":[{"value":"1433-7851","type":"print"},{"value":"1521-3773","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,28]]},"assertion":[{"value":"2026-05-23","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-08-15","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-08-28","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e1329257"}}