{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T23:30:29Z","timestamp":1790811029090,"version":"4.1.0"},"reference-count":59,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2017,1,29]],"date-time":"2017-01-29T00:00:00Z","timestamp":1485648000000},"content-version":"vor","delay-in-days":28,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pigment Cell Melanoma Res"],"published-print":{"date-parts":[[2017,1]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>Oculocutaneous albinism type 1 (<jats:styled-content style=\"fixed-case\">OCA<\/jats:styled-content>1) is an autosomal recessive disorder caused by mutations in the tyrosinase gene. Two subtypes of<jats:styled-content style=\"fixed-case\">OCA<\/jats:styled-content>1 have been described: severe<jats:styled-content style=\"fixed-case\">OCA<\/jats:styled-content>1A with complete absence of tyrosinase activity and less severe<jats:styled-content style=\"fixed-case\">OCA<\/jats:styled-content>1B with residual tyrosinase activity. Here, we characterize the recombinant human tyrosinase intramelanosomal domain and mutant variants, which mimic genetic changes in both subtypes of<jats:styled-content style=\"fixed-case\">OCA<\/jats:styled-content>1 patients. Proteins were prepared using site\u2010directed mutagenesis, expressed in insect larvae, purified by chromatography, and characterized by enzymatic activities, tryptophan fluorescence, and Gibbs free energy changes. The<jats:styled-content style=\"fixed-case\">OCA<\/jats:styled-content>1A mutants showed very low protein expression and protein yield and are enzymatically inactive. Mutants mimicking<jats:styled-content style=\"fixed-case\">OCA<\/jats:styled-content>1B were biochemically similar to the wild type, but exhibited lower specific activities and protein stabilities. The results are consistent with clinical data, which indicates that<jats:styled-content style=\"fixed-case\">OCA<\/jats:styled-content>1A mutations inactivate tyrosinase and result in severe phenotype, while<jats:styled-content style=\"fixed-case\">OCA<\/jats:styled-content>1B mutations partially inactivate tyrosinase and result in<jats:styled-content style=\"fixed-case\">OCA<\/jats:styled-content>1B albinism.<\/jats:p>","DOI":"10.1111\/pcmr.12546","type":"journal-article","created":{"date-parts":[[2016,10,24]],"date-time":"2016-10-24T16:22:41Z","timestamp":1477326161000},"page":"41-52","source":"Crossref","is-referenced-by-count":60,"title":["Oculocutaneous albinism type 1: link between mutations, tyrosinase conformational stability, and enzymatic activity"],"prefix":"10.1111","volume":"30","author":[{"given":"Monika B.","family":"Dolinska","sequence":"first","affiliation":[{"name":"National Eye Institute National Institutes of Health Bethesda MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicole J.","family":"Kus","sequence":"additional","affiliation":[{"name":"National Eye Institute National Institutes of Health Bethesda MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S. Katie","family":"Farney","sequence":"additional","affiliation":[{"name":"National Eye Institute National Institutes of Health Bethesda MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul T.","family":"Wingfield","sequence":"additional","affiliation":[{"name":"National Institute of Artritis and Musculoskeletal and Skin Diseases National Institutes of Health Bethesda MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian P.","family":"Brooks","sequence":"additional","affiliation":[{"name":"National Eye Institute National Institutes of Health Bethesda MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuri V.","family":"Sergeev","sequence":"additional","affiliation":[{"name":"National Eye Institute National Institutes of Health Bethesda MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2017,1,29]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2015-09-671636"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng576"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.275.16.12281"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.201506994"},{"key":"e_1_2_6_6_1","first-page":"1145","article-title":"Mutation in and lack of expression of tyrosinase\u2010related protein\u20101 (TRP\u20101) in melanocytes from an individual with brown oculocutaneous albinism: a new subtype of albinism classified as \u201cOCA3\u201d","volume":"58","author":"Boissy R.E.","year":"1996","journal-title":"Am. J. Hum. Genet."},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.20171"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.32939"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2011.05.009"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0084494"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/cbdd.12306"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI115075"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1186\/1750-1172-2-43"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2013.01.006"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.85.19.7241"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.97.11.5889"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M008703200"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/0003-9861(78)90183-2"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.2008.065961"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/jid.2008.109"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.07-0791"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.1111\/1523-1747.ep12263562"},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.1111\/pcmr.12253"},{"key":"e_1_2_6_24_1","doi-asserted-by":"publisher","DOI":"10.1271\/bbb.68.1984"},{"key":"e_1_2_6_25_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2005-11-4377"},{"key":"e_1_2_6_26_1","doi-asserted-by":"publisher","DOI":"10.1111\/1523-1747.ep12546765"},{"key":"e_1_2_6_27_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-0004.1986.tb00769.x"},{"key":"e_1_2_6_28_1","first-page":"19","article-title":"Non\u2010random distribution of missense mutations within the human tyrosinase gene in type I (tyrosinase\u2010related) oculocutaneous albinism","volume":"8","author":"King R.A.","year":"1991","journal-title":"Mol. Biol. Med."},{"key":"e_1_2_6_29_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00439-003-0998-1"},{"key":"e_1_2_6_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pep.2003.11.015"},{"key":"e_1_2_6_31_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng1229"},{"key":"e_1_2_6_32_1","doi-asserted-by":"publisher","DOI":"10.1099\/mic.0.2007\/006833-0"},{"key":"e_1_2_6_33_1","doi-asserted-by":"publisher","DOI":"10.1086\/301603"},{"key":"e_1_2_6_34_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.84.19.6663"},{"key":"e_1_2_6_35_1","doi-asserted-by":"publisher","DOI":"10.1111\/pcmr.12167"},{"key":"e_1_2_6_36_1","doi-asserted-by":"publisher","DOI":"10.1086\/499338"},{"key":"e_1_2_6_37_1","doi-asserted-by":"publisher","DOI":"10.1086\/324340"},{"key":"e_1_2_6_38_1","doi-asserted-by":"publisher","DOI":"10.1093\/molbev\/msl203"},{"key":"e_1_2_6_39_1","doi-asserted-by":"publisher","DOI":"10.1034\/j.1600-0749.2000.130503.x"},{"key":"e_1_2_6_40_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0749.1992.tb00549.x"},{"key":"e_1_2_6_41_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.32654"},{"key":"e_1_2_6_42_1","doi-asserted-by":"publisher","DOI":"10.1086\/301757"},{"key":"e_1_2_6_43_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI59372"},{"key":"e_1_2_6_44_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF01913172"},{"key":"e_1_2_6_45_1","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1016\/S1016-8478(23)13278-X","article-title":"Prevalent and novel mutations of the tyrosinase gene in Korean patients with tyrosinase\u2010deficient oculocutaneous albinism","volume":"7","author":"Park S.K.","year":"1997","journal-title":"Mol. Cells"},{"key":"e_1_2_6_46_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M413087200"},{"key":"e_1_2_6_47_1","first-page":"951","article-title":"The great DOPA mystery: the source and significance of DOPA in phase I melanogenesis","volume":"45","author":"Riley P. A.","year":"1999","journal-title":"Cell Mol. Biol. (Noisy\u2010le\u2010grand)"},{"key":"e_1_2_6_48_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0749.2005.00240.x"},{"key":"e_1_2_6_49_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1432-1033.1990.tb15510.x"},{"key":"e_1_2_6_50_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.22315"},{"key":"e_1_2_6_51_1","doi-asserted-by":"publisher","DOI":"10.1111\/1523-1747.ep12319351"},{"key":"e_1_2_6_52_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng835"},{"key":"e_1_2_6_53_1","doi-asserted-by":"publisher","DOI":"10.1034\/j.1600-0749.13.s8.23.x"},{"key":"e_1_2_6_54_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.01-0216com"},{"key":"e_1_2_6_55_1","doi-asserted-by":"crossref","first-page":"23707","DOI":"10.1016\/S0021-9258(18)35895-2","article-title":"Mutational mapping of the catalytic activities of human tyrosinase","volume":"267","author":"Tripathi R.K.","year":"1992","journal-title":"J. Biol. Chem."},{"key":"e_1_2_6_56_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.1320430523"},{"key":"e_1_2_6_57_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1098-1004(199912)14:6<542::AID-HUMU14>3.0.CO;2-3"},{"key":"e_1_2_6_58_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0749.2005.00288.x"},{"key":"e_1_2_6_59_1","doi-asserted-by":"publisher","DOI":"10.1038\/jid.2013.49"},{"key":"e_1_2_6_60_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng1087"}],"container-title":["Pigment Cell &amp; Melanoma Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fpcmr.12546","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fpcmr.12546","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/pcmr.12546","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,6,20]],"date-time":"2024-06-20T04:36:05Z","timestamp":1718858165000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/pcmr.12546"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,1]]},"references-count":59,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2017,1]]}},"alternative-id":["10.1111\/pcmr.12546"],"URL":"https:\/\/doi.org\/10.1111\/pcmr.12546","archive":["Portico"],"relation":{},"ISSN":["1755-1471","1755-148X"],"issn-type":[{"value":"1755-1471","type":"print"},{"value":"1755-148X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,1]]}}}