Oculocutaneous albinism type 1: link between mutations, tyrosinase conformational stability, and enzymatic activity.
Pigment Cell Melanoma Res
; 30(1): 41-52, 2017 01.
Article
em En
| MEDLINE
| ID: mdl-27775880
ABSTRACT
Oculocutaneous albinism type 1 (OCA1) is an autosomal recessive disorder caused by mutations in the tyrosinase gene. Two subtypes of OCA1 have been described severe OCA1A with complete absence of tyrosinase activity and less severe OCA1B with residual tyrosinase activity. Here, we characterize the recombinant human tyrosinase intramelanosomal domain and mutant variants, which mimic genetic changes in both subtypes of OCA1 patients. Proteins were prepared using site-directed mutagenesis, expressed in insect larvae, purified by chromatography, and characterized by enzymatic activities, tryptophan fluorescence, and Gibbs free energy changes. The OCA1A mutants showed very low protein expression and protein yield and are enzymatically inactive. Mutants mimicking OCA1B 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 OCA1A mutations inactivate tyrosinase and result in severe phenotype, while OCA1B mutations partially inactivate tyrosinase and result in OCA1B albinism.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Conformação Proteica
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Albinismo Oculocutâneo
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Monofenol Mono-Oxigenase
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Mutação
Limite:
Humans
Idioma:
En
Revista:
Pigment Cell Melanoma Res
Assunto da revista:
NEOPLASIAS
Ano de publicação:
2017
Tipo de documento:
Article
País de afiliação:
Estados Unidos