{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,19]],"date-time":"2026-02-19T03:36:52Z","timestamp":1771472212376,"version":"3.50.1"},"reference-count":45,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2025,1,22]],"date-time":"2025-01-22T00:00:00Z","timestamp":1737504000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000053","name":"National Eye Institute","doi-asserted-by":"publisher","award":["ZIA EY000476\u201010"],"award-info":[{"award-number":["ZIA EY000476\u201010"]}],"id":[{"id":"10.13039\/100000053","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Protein Science"],"published-print":{"date-parts":[[2025,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Oculocutaneous albinism is an autosomal recessive inherited disorder associated with mutations in the <jats:italic>TYR<\/jats:italic> gene. A single missense change in the tyrosinase (Tyr) could result in partial or complete loss of catalytic activity. The effect of two genetic mutations in the same Tyr as the molecule is less studied. Here, we study single mutation variants, R217Q, R402Q, and a double mutant variant, R217Q\/R402Q, to establish a link between alterations at the level of the atomic model of the protein and the disease phenotype. Human recombinant intra\u2010melanosomal Tyr domains of Tyr and three mutant variants were expressed in <jats:italic>T. ni.<\/jats:italic> Larvae were purified using the combination of IMAC and SEC, and diphenolase activities were measured. The Tyr homology model was equilibrated using 100\u2009ns molecular dynamics and analyzed using computational methods. The purified R217Q and R217Q\/R402Q variants show decreased catalytic activities compared to those of the Tyr and R402Q variants. The R217Q\/R402Q variant has the lowest protein activity and is significantly reduced.<\/jats:p>","DOI":"10.1002\/pro.70029","type":"journal-article","created":{"date-parts":[[2025,1,22]],"date-time":"2025-01-22T12:12:24Z","timestamp":1737547944000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Human recombinant tyrosinase destabilization caused by the double mutation <scp>R217Q<\/scp>\/<scp>R402Q<\/scp>"],"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":[{"role":"author","vocabulary":"crossref"}]},{"given":"Narin","family":"Sheri","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology &amp; Visual Sciences University of Alberta  Edmonton Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ian","family":"MacDonald","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology &amp; Visual Sciences University of Alberta  Edmonton Canada"},{"name":"Department of Ophthalmology University of Montreal  Montreal Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7204-6572","authenticated-orcid":false,"given":"Yuri V.","family":"Sergeev","sequence":"additional","affiliation":[{"name":"Protein Biochemistry and Molecular Modeling Group, OGVFB National Eye Institute, National Institutes of Health  Bethesda Maryland USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,1,22]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-019-51768-8"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.exer.2023.109761"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms25137082"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0175598"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0084494"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/pcmr.12546"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms25063373"},{"issue":"6","key":"e_1_2_8_9_1","first-page":"621","article-title":"Dynamic analysis of human tyrosinase intra\u2010melanosomal domain and mutant variants to further understand oculocutaneous albinism type 1","volume":"7","author":"Farney 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