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La estructura del dominio Cnx1G ligado a la molibdopterina enlaza el metabolismo del molibdeno y el cobre
Jochen Kuper1, Angel Llamas, Hans-Jürgen Hecht
1Department of Plant Biology, Technical University, Spielmannstrasse 7, D-38106 Braunschweig, Germany.
Nature
|August 13, 2004
Resumen
El cofactor de molibdeno, esencial para muchas enzimas, se une a la molibdopterina. Nuevas estructuras cristalinas revelan el cobre.
Área de la Ciencia:
- Bioquímica y Biología Molecular.
- Mecanismos de las enzimas.
- Estructura y función de las metalloenzimas.
Sus antecedentes:
- El cofactor de molibdeno (Moco) es crucial para las enzimas dependientes del molibdeno, con un ligando de piranopterina que coordina el molibdeno.
- La biosíntesis de moco se conserva en todas las especies, con la proteína vegetal Cnx1 que cataliza la inserción de molibdeno en la molibdopterin.
- El dominio Cnx1 G (Cnx1G) se une a la molibdopterina y está involucrado en la catálisis de inserción de molibdeno.
Objetivo del estudio:
- Para aclarar la base estructural de la unión de la molibdopterina y la inserción de molibdeno por Cnx1G.
- Para investigar el papel de la molibdopterina-AMP, un intermediario clave en la biosíntesis de Moco.
- Explorar las posibles interacciones entre las vías metabólicas del molibdeno y el cobre.
Principales métodos:
- Determinación de la estructura cristalina de alta resolución de Cnx1G en complejo con molibdopterina y molibdopterina-AMP.
- Ensayos bioquímicos para evaluar la actividad de Cnx1G y la inhibición del cobre.
- Análisis estructural para identificar iones metálicos unidos y su coordinación.
Principales resultados:
- Las estructuras cristalinas revelaron Cnx1G unido tanto a la molibdopterina como al intermediario molibdopterina-AMP.
- Inesperadamente, se identificaron iones de cobre unidos a los sulfuros de metiolato de molibdopterina en ambos complejos.
- Se encontró que el cobre inhibe la actividad de Cnx1G, lo que sugiere un vínculo entre el cobre y la biosíntesis de Moco.
Conclusiones:
- Las estructuras proporcionan información detallada sobre la unión de la molibdopterina y el mecanismo catalítico de Cnx1G.
- Los hallazgos revelan un nuevo vínculo molecular entre el metabolismo del molibdeno y el cobre.
- El efecto inhibidor del cobre sobre Cnx1G destaca su papel regulador en la biosíntesis de Moco.
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