Publication

Structure of Human Tyrosinase Related Protein 1 Reveals a Binuclear Zinc Active Site Important for Melanogenesis

Lai, X., Wichers, H. J., Soler-Lopez, M. & Dijkstra, B. W., 7-Aug-2017, In : Angewandte Chemie-International Edition. 56, 33, p. 9812-9815 4 p.

Research output: Contribution to journalArticleAcademicpeer-review

APA

Lai, X., Wichers, H. J., Soler-Lopez, M., & Dijkstra, B. W. (2017). Structure of Human Tyrosinase Related Protein 1 Reveals a Binuclear Zinc Active Site Important for Melanogenesis. Angewandte Chemie-International Edition, 56(33), 9812-9815. https://doi.org/10.1002/anie.201704616

Author

Lai, Xuelei ; Wichers, Harry J. ; Soler-Lopez, Montserrat ; Dijkstra, Bauke W. / Structure of Human Tyrosinase Related Protein 1 Reveals a Binuclear Zinc Active Site Important for Melanogenesis. In: Angewandte Chemie-International Edition. 2017 ; Vol. 56, No. 33. pp. 9812-9815.

Harvard

Lai, X, Wichers, HJ, Soler-Lopez, M & Dijkstra, BW 2017, 'Structure of Human Tyrosinase Related Protein 1 Reveals a Binuclear Zinc Active Site Important for Melanogenesis', Angewandte Chemie-International Edition, vol. 56, no. 33, pp. 9812-9815. https://doi.org/10.1002/anie.201704616

Standard

Structure of Human Tyrosinase Related Protein 1 Reveals a Binuclear Zinc Active Site Important for Melanogenesis. / Lai, Xuelei; Wichers, Harry J.; Soler-Lopez, Montserrat; Dijkstra, Bauke W.

In: Angewandte Chemie-International Edition, Vol. 56, No. 33, 07.08.2017, p. 9812-9815.

Research output: Contribution to journalArticleAcademicpeer-review

Vancouver

Lai X, Wichers HJ, Soler-Lopez M, Dijkstra BW. Structure of Human Tyrosinase Related Protein 1 Reveals a Binuclear Zinc Active Site Important for Melanogenesis. Angewandte Chemie-International Edition. 2017 Aug 7;56(33):9812-9815. https://doi.org/10.1002/anie.201704616


BibTeX

@article{6fc78803636b4de7b13f6f32e40a71b2,
title = "Structure of Human Tyrosinase Related Protein 1 Reveals a Binuclear Zinc Active Site Important for Melanogenesis",
abstract = "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.",
keywords = "albinism, human tyrosinase, melanogenesis, structure elucidation, zinc-copper enzymes, DHICA OXIDASE, ALBINISM, TYRP1, HAIR",
author = "Xuelei Lai and Wichers, {Harry J.} and Montserrat Soler-Lopez and Dijkstra, {Bauke W.}",
year = "2017",
month = "8",
day = "7",
doi = "10.1002/anie.201704616",
language = "English",
volume = "56",
pages = "9812--9815",
journal = "Angewandte Chemie - International Edition",
issn = "1433-7851",
publisher = "WILEY-V C H VERLAG GMBH",
number = "33",

}

RIS

TY - JOUR

T1 - Structure of Human Tyrosinase Related Protein 1 Reveals a Binuclear Zinc Active Site Important for Melanogenesis

AU - Lai, Xuelei

AU - Wichers, Harry J.

AU - Soler-Lopez, Montserrat

AU - Dijkstra, Bauke W.

PY - 2017/8/7

Y1 - 2017/8/7

N2 - 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.

AB - 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.

KW - albinism

KW - human tyrosinase

KW - melanogenesis

KW - structure elucidation

KW - zinc-copper enzymes

KW - DHICA OXIDASE

KW - ALBINISM

KW - TYRP1

KW - HAIR

U2 - 10.1002/anie.201704616

DO - 10.1002/anie.201704616

M3 - Article

VL - 56

SP - 9812

EP - 9815

JO - Angewandte Chemie - International Edition

JF - Angewandte Chemie - International Edition

SN - 1433-7851

IS - 33

ER -

ID: 96960716