{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T02:50:44Z","timestamp":1787539844137,"version":"build-2736575974"},"reference-count":57,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2025,7,16]],"date-time":"2025-07-16T00:00:00Z","timestamp":1752624000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["ZIA EY000476\u201010"],"award-info":[{"award-number":["ZIA EY000476\u201010"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Protein Science"],"published-print":{"date-parts":[[2025,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Oculocutaneous albinism type 1 is a genetic disorder caused by the disruption of tyrosinase activity in the melanogenesis pathway. The tyrosinase's intramelanosomal domain can be subdivided into the catalytic and Cys\u2010rich subdomains, integral for protein stability and catalytic activity. To understand the movement in the tyrosinase intra\u2010melanosomal subdomains and their link to its catalytic activity, we perform essential dynamics on homology models for tyrosinase and the mutant variants R217Q, R402Q, and R217Q\/R402Q. Dimensional reduction techniques, such as principal component analysis (PCA), are fundamental to systematically comprehending collective movements in protein structure. The alpha\u2010carbon atomic coordinates for all residues across a 100\u2010ns molecular dynamics trajectory were input into the PCA function, and the results were analyzed alongside correlated movements and free energy profiles for each protein structure. The PCA\u2010identified coordinated movement underlying the stable conformations of wild\u2010type tyrosinase arises within the H9 and H10 helices, which are proximal to the flexible tunnel system and the interface of the catalytic and Cys\u2010rich subdomains. In contrast, genetic mutations R217Q and R217Q\/R402Q disrupt the coordinated movement of the tyrosinase intra\u2010melanosomal domain, indicating a cause of mutant variant instability.<\/jats:p>","DOI":"10.1002\/pro.70209","type":"journal-article","created":{"date-parts":[[2025,7,17]],"date-time":"2025-07-17T05:20:32Z","timestamp":1752729632000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Genetic mutations disrupt the coordinated mode of tyrosinase's intra\u2010melanosomal domain"],"prefix":"10.1002","volume":"34","author":[{"given":"Sarah","family":"Toay","sequence":"first","affiliation":[{"name":"Protein Biochemistry and Molecular Modeling Group, OGVFB National Eye Institute, National Institutes of Health  Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7204-6572","authenticated-orcid":false,"given":"Yuri 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