{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,11]],"date-time":"2026-02-11T13:49:14Z","timestamp":1770817754913,"version":"3.50.1"},"reference-count":32,"publisher":"Walter de Gruyter GmbH","issue":"1","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2017,12,20]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Tyrosinase, a melanosomal glycoenzyme, catalyzes initial steps of the melanin biosynthesis. While glycosylation was previously studied<jats:italic>in vivo<\/jats:italic>, we present three recombinant mutant variants of human tyrosinase, which were obtained using multiple site-directed mutagenesis, expressed in insect larvae, purified and characterized biochemically. The mutagenesis demonstrated the reduced protein expression and enzymatic activity due to possible loss of protein stability and protein degradation. However, the complete deglycosylation of asparagine residues<jats:italic>in vitro<\/jats:italic>, including the residue in position 371, interrupts tyrosinase function, which is consistent with a melanin loss in oculocutaneous albinism type 1 (OCA1) patients.<\/jats:p>","DOI":"10.1515\/hsz-2017-0178","type":"journal-article","created":{"date-parts":[[2017,8,31]],"date-time":"2017-08-31T10:00:44Z","timestamp":1504173644000},"page":"73-77","source":"Crossref","is-referenced-by-count":10,"title":["The consequences of deglycosylation of recombinant intra-melanosomal domain of human tyrosinase"],"prefix":"10.1515","volume":"399","author":[{"given":"Monika B.","family":"Dolinska","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuri V.","family":"Sergeev","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"374","reference":[{"key":"ref01","doi-asserted-by":"crossref","first-page":"8169","DOI":"10.1074\/jbc.275.11.8169","article-title":"Mutations at critical N-glycosylation sites reduce tyrosinase activity by altering folding and quality control","volume":"275","year":"2000","journal-title":"J. Biol. Chem."},{"key":"ref141","doi-asserted-by":"crossref","first-page":"865","DOI":"10.1002\/ajmg.1320430523","article-title":"Tyrosinase gene mutations in type I (tyrosinase-deficient) oculocutaneous albinism define two clusters of missense substitutions","volume":"43","year":"1992","journal-title":"Am. J. Med. Genet."},{"key":"ref111","doi-asserted-by":"crossref","first-page":"15735","DOI":"10.1074\/jbc.M300658200","article-title":"Conformation-dependent post-translational glycosylation of tyrosinase. Requirement of a specific interaction involving the CuB metal binding site","volume":"278","year":"2003","journal-title":"J. Biol. Chem."},{"key":"ref21","doi-asserted-by":"crossref","first-page":"e84494","DOI":"10.1371\/journal.pone.0084494","article-title":"Albinism-causing mutations in recombinant human tyrosinase alter intrinsic enzymatic activity","volume":"9","year":"2014","journal-title":"PLoS One"},{"key":"ref71","doi-asserted-by":"crossref","first-page":"e1002285","DOI":"10.1371\/journal.pcbi.1002285","article-title":"Integrating bioinformatics tools to handle glycosylation","volume":"7","year":"2011","journal-title":"PLoS Comput. Biol."},{"key":"ref171","doi-asserted-by":"crossref","first-page":"1163","DOI":"10.1016\/j.cell.2012.11.012","article-title":"Cleaning up: ER-associated degradation to the rescue","volume":"151","year":"2012","journal-title":"Cell"},{"key":"ref61","doi-asserted-by":"crossref","first-page":"196","DOI":"10.1111\/1523-1747.ep12263562","article-title":"Functional analysis of tyrosinase isozymes of cultured malignant melanoma cells during the recovery period following interrupted melanogenesis induced by glycosylation inhibitors","volume":"83","year":"1984","journal-title":"J. Invest. Dermatol."},{"key":"ref231","doi-asserted-by":"crossref","first-page":"e1002285","DOI":"10.1371\/journal.pcbi.1002285","article-title":"Integrating bioinformatics tools to handle glycosylation","volume":"7","year":"2011","journal-title":"PLoS Comput. Biol."},{"key":"ref201","doi-asserted-by":"crossref","first-page":"1017","DOI":"10.1016\/0955-0674(92)90134-X","article-title":"Glycosylation","volume":"4","year":"1992","journal-title":"Curr. Opin. Cell Biol."},{"key":"ref11","doi-asserted-by":"crossref","first-page":"1163","DOI":"10.1016\/j.cell.2012.11.012","article-title":"Cleaning up: ER-associated degradation to the rescue","volume":"151","year":"2012","journal-title":"Cell"},{"key":"ref41","doi-asserted-by":"crossref","first-page":"1017","DOI":"10.1016\/0955-0674(92)90134-X","article-title":"Glycosylation","volume":"4","year":"1992","journal-title":"Curr. Opin. Cell Biol."},{"key":"ref101","doi-asserted-by":"crossref","first-page":"750","DOI":"10.1111\/j.1755-148X.2009.00636.x","article-title":"New insights into the active site structure and catalytic mechanism of tyrosinase and its related proteins","volume":"22","year":"2009","journal-title":"Pigment Cell Melanoma Res."},{"key":"ref251","doi-asserted-by":"crossref","first-page":"659","DOI":"10.1042\/bj3440659","article-title":"Protein specific N-glycosylation of tyrosinase and tyrosinase-related protein-1 in B16 mouse melanoma cells","volume":"344","year":"1999","journal-title":"Biochem J."},{"key":"ref121","doi-asserted-by":"crossref","first-page":"827","DOI":"10.1002\/humu.22315","article-title":"DNA variations in oculocutaneous albinism: an updated mutation list and current outstanding issues in molecular diagnostics","volume":"34","year":"2013","journal-title":"Hum. Mutat."},{"key":"ref221","doi-asserted-by":"crossref","first-page":"196","DOI":"10.1111\/1523-1747.ep12263562","article-title":"Functional analysis of tyrosinase isozymes of cultured malignant melanoma cells during the recovery period following interrupted melanogenesis induced by glycosylation inhibitors","volume":"83","year":"1984","journal-title":"J. Invest. Dermatol."},{"key":"ref261","doi-asserted-by":"crossref","first-page":"750","DOI":"10.1111\/j.1755-148X.2009.00636.x","article-title":"New insights into the active site structure and catalytic mechanism of tyrosinase and its related proteins","volume":"22","year":"2009","journal-title":"Pigment Cell Melanoma Res."},{"key":"ref191","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1111\/pcmr.12546","article-title":"Oculocutaneous albinism type 1: link between mutations, tyrosinase conformational stability, and enzymatic activity","volume":"30","year":"2017","journal-title":"Pigment Cell Melanoma Res."},{"key":"ref281","doi-asserted-by":"crossref","first-page":"827","DOI":"10.1002\/humu.22315","article-title":"DNA variations in oculocutaneous albinism: an updated mutation list and current outstanding issues in molecular diagnostics","volume":"34","year":"2013","journal-title":"Hum. Mutat."},{"key":"ref151","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1111\/j.1600-0749.2005.00288.x","article-title":"Tyrosinase maturation through the mammalian secretory pathway: bringing color to life","volume":"19","year":"2006","journal-title":"Pigment Cell Res."},{"key":"ref181","doi-asserted-by":"crossref","first-page":"e84494","DOI":"10.1371\/journal.pone.0084494","article-title":"Albinism-causing mutations in recombinant human tyrosinase alter intrinsic enzymatic activity","volume":"9","year":"2014","journal-title":"PLoS One"},{"key":"ref241","doi-asserted-by":"crossref","first-page":"818","DOI":"10.3892\/mmr.2013.1602","article-title":"Glycosylation of tyrosinase is a determinant of melanin production in cultured melanoma cells","volume":"8","year":"2013","journal-title":"Mol. Med. Rep."},{"key":"ref131","doi-asserted-by":"crossref","first-page":"2937","DOI":"10.1242\/jcs.01154","article-title":"Carbohydrates act as sorting determinants in ER-associated degradation of tyrosinase","volume":"117","year":"2004","journal-title":"J. Cell Sci."},{"key":"ref161","doi-asserted-by":"crossref","first-page":"8169","DOI":"10.1074\/jbc.275.11.8169","article-title":"Mutations at critical N-glycosylation sites reduce tyrosinase activity by altering folding and quality control","volume":"275","year":"2000","journal-title":"J. Biol. Chem."},{"key":"ref301","doi-asserted-by":"crossref","first-page":"865","DOI":"10.1002\/ajmg.1320430523","article-title":"Tyrosinase gene mutations in type I (tyrosinase-deficient) oculocutaneous albinism define two clusters of missense substitutions","volume":"43","year":"1992","journal-title":"Am. J. Med. Genet."},{"key":"ref291","doi-asserted-by":"crossref","first-page":"2937","DOI":"10.1242\/jcs.01154","article-title":"Carbohydrates act as sorting determinants in ER-associated degradation of tyrosinase","volume":"117","year":"2004","journal-title":"J. Cell Sci."},{"key":"ref211","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1016\/S0076-6879(87)42024-7","article-title":"Mammalian monophenol monooxygenase (tyrosinase): purification, properties, and reactions catalyzed","volume":"142","year":"1987","journal-title":"Methods Enzymol."},{"key":"ref311","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1111\/j.1600-0749.2005.00288.x","article-title":"Tyrosinase maturation through the mammalian secretory pathway: bringing color to life","volume":"19","year":"2006","journal-title":"Pigment Cell Res."},{"key":"ref31","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1111\/pcmr.12546","article-title":"Oculocutaneous albinism type 1: link between mutations, tyrosinase conformational stability, and enzymatic activity","volume":"30","year":"2017","journal-title":"Pigment Cell Melanoma Res."},{"key":"ref51","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1016\/S0076-6879(87)42024-7","article-title":"Mammalian monophenol monooxygenase (tyrosinase): purification, properties, and reactions catalyzed","volume":"142","year":"1987","journal-title":"Methods Enzymol."},{"key":"ref81","doi-asserted-by":"crossref","first-page":"818","DOI":"10.3892\/mmr.2013.1602","article-title":"Glycosylation of tyrosinase is a determinant of melanin production in cultured melanoma cells","volume":"8","year":"2013","journal-title":"Mol. Med. Rep."},{"key":"ref91","doi-asserted-by":"crossref","first-page":"659","DOI":"10.1042\/bj3440659","article-title":"Protein specific N-glycosylation of tyrosinase and tyrosinase-related protein-1 in B16 mouse melanoma cells","volume":"344","year":"1999","journal-title":"Biochem J."},{"key":"ref271","doi-asserted-by":"crossref","first-page":"15735","DOI":"10.1074\/jbc.M300658200","article-title":"Conformation-dependent post-translational glycosylation of tyrosinase. Requirement of a specific interaction involving the CuB metal binding site","volume":"278","year":"2003","journal-title":"J. Biol. Chem."}],"container-title":["Biological Chemistry"],"original-title":[],"link":[{"URL":"http:\/\/www.degruyter.com\/view\/j\/bchm.2018.399.issue-1\/hsz-2017-0178\/hsz-2017-0178.xml","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/www.degruyter.com\/view\/j\/bchm.2018.399.issue-1\/hsz-2017-0178\/hsz-2017-0178.xml","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,8,2]],"date-time":"2022-08-02T00:38:31Z","timestamp":1659400711000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.degruyter.com\/document\/doi\/10.1515\/hsz-2017-0178\/html"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,12,20]]},"references-count":32,"journal-issue":{"issue":"1"},"URL":"https:\/\/doi.org\/10.1515\/hsz-2017-0178","relation":{},"ISSN":["1437-4315","1431-6730"],"issn-type":[{"value":"1437-4315","type":"electronic"},{"value":"1431-6730","type":"print"}],"subject":[],"published":{"date-parts":[[2017,12,20]]}}}