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Las propiedades duales de unión nanomolar y picomolar Zn (II) de la metalotioneína
1Department of Preventive Medicine and Community Health, The University of Texas Medical Branch, Galveston, Texas 77555, USA.
Journal of the American Chemical Society
|August 19, 2007
Resumen
La metalotioneína se une a los iones de zinc con diferentes afinidades, regulando la disponibilidad de zinc en las células. La tioneína, la apoproteína, controla la liberación de zinc, lo que afecta la reactividad del tiol y los procesos biológicos.
Área de la Ciencia:
- La bioquímica es la bioquímica.
- Química de las metaloproteínas
- La homeostasis del zinc celular es la homeostasis del zinc celular.
Sus antecedentes:
- La metalotioneína humana contiene siete iones Zn(II) en entornos de coordinación de tetraciolato dentro de sus clústeres Zn(3) S(9) y Zn(4) S(11 .
- La metallotioneína juega un papel crucial en el búfer de zinc celular y la desintoxicación.
Objetivo del estudio:
- Investigar las afinidades de unión de los iones Zn(II) con la tioneína (la apoproteína) y la metalotioneína.
- Aclarar el papel de la metalotioneína y la tioneína en la regulación de las concentraciones celulares de zinc libre y la reactividad del tiol.
Principales métodos:
- Análisis de la asociación de Zn(II) con la tioneína y la disociación de la metalotioneína utilizando agentes quelantes fluorescentes (FluoZin-3 y RhodZin-3).
- Determinación de las afinidades de unión de Zn(II) (log aparente K) y caracterización de las diferentes especies de unión de Zn(II) (Zn(4) T a Zn(7) T).
Principales resultados:
- La unión de Zn(II) a la metalotioneína exhibe al menos tres clases de sitios con afinidades que difieren en cuatro órdenes de magnitud.
- Cuatro iones Zn(II) están fuertemente unidos (log K ≈ 11.8), mientras que uno está débilmente unido (log K ≈ 7.7), lo que permite que la metalotioneína actúe como donante de zinc.
- Las especies predominantes en las concentraciones celulares son Zn(5) T y Zn(6) T (log K ≈ 10). La tioneína regula los niveles libres de Zn (II), lo que influye en las tasas de oxidación del tiol.
Conclusiones:
- Las distintas afinidades de unión Zn(II) de la metallotioneína le permiten funcionar como un potente quelante y un donante de zinc.
- La relación entre la tioneína y la metalotioneína controla críticamente los niveles libres de Zn{II} (pZn), lo que corresponde a las necesidades celulares.
- La estructura molecular y la química redox de la metalotioneína y la tioneína dictan la disponibilidad de ZnII para procesos biológicos esenciales.
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