Structure of Human Tyrosinase Related Protein 1 Reveals a Binuclear Zinc Active Site Important for Melanogenesis
| العنوان: | Structure of Human Tyrosinase Related Protein 1 Reveals a Binuclear Zinc Active Site Important for Melanogenesis |
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| المؤلفون: | Xuelei Lai, Montserrat Soler-López, Bauke W. Dijkstra, Harry J. Wichers |
| المساهمون: | Univ Groningen, Lab Biophys Chem, Nijenborgh 7, NL-9747 AG Groningen, Netherlands, European Synchrotron Radiation Facility (ESRF), Wageningen Food & Biobased Res, Bornse Weilanden 9, NL-6708 WG Wageningen, Netherlands, X-ray Crystallography |
| المصدر: | Angewandte Chemie International Edition Angewandte Chemie International Edition, Wiley-VCH Verlag, 2017, 56 (33), pp.9812-9815. ⟨10.1002/anie.201704616⟩ Angewandte Chemie-International Edition, 56(33), 9812-9815. WILEY-V C H VERLAG GMBH Angewandte Chemie (International Ed. in English) Angewandte Chemie-International Edition, 56(33), 9812-9815 Angewandte Chemie-International Edition 56 (2017) 33 'Angewandte Chemie International Edition ', vol: 56, pages: 9812-9815 (2017) |
| بيانات النشر: | WILEY-V C H VERLAG GMBH, 2017. |
| سنة النشر: | 2017 |
| مصطلحات موضوعية: | Models, Molecular, 0301 basic medicine, melanogenesis, zinc-copper enzymes, Protein Conformation, [SDV]Life Sciences [q-bio], Tyrosinase, chemistry.chemical_element, albinism, Zinc, Catalysis, Melanin, ALBINISM, 03 medical and health sciences, TYRP1, medicine, Humans, HAIR, Pigmentation disorder, Food, Health & Consumer Research, VLAG, chemistry.chemical_classification, Binding Sites, Membrane Glycoproteins, biology, Chemistry, Communication, structure elucidation, Active site, human tyrosinase, General Chemistry, Enzyme Structure and Function | Very Important Paper, medicine.disease, Communications, 3. Good health, Health & Consumer Research, 030104 developmental biology, Enzyme, Biochemistry, Food, Mutation, biology.protein, Albinism, DHICA OXIDASE, Oxidoreductases, zinc–copper enzymes |
| الوصف: | International audience; Tyrosinase-related protein 1 (TYRP1) is one of three tyrosinase-like glycoenzymes in human melanocytes that are key to the production of melanin, the compound responsible for the pigmentation of skin, eye, and hair. Difficulties with producing these enzymes in pure form have hampered the understanding of their activity and the effect of mutations that cause albinism and pigmentation disorders. Herein we show that the typical tyrosinase-like subdomain of TYRP1 contains two zinc ions in the active site instead of copper ions as found in tyrosinases, which explains why TYRP1 does not exhibit tyrosinase redox activity. In addition, the structures reveal for the first time that the Cys-rich subdomain, which is unique to vertebrate melanogenic proteins, has an epidermal growth factor-like fold and is tightly associated with the tyrosinase subdomain. Our structures suggest that most albinism-related mutations of TYRP1 affect its stability or activity |
| وصف الملف: | application/pdf; application/octet-stream |
| اللغة: | English |
| تدمد: | 1521-3773 1433-7851 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::acd9cb82191fce84fc010541b57af366Test https://research.rug.nl/en/publications/6fc78803-636b-4de7-b13f-6f32e40a71b2Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....acd9cb82191fce84fc010541b57af366 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15213773 14337851 |
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