Predicción computacional de la estructura terciaria de la iduronato 2-sulfato sulfatasa humana

Homero Sáenz, Leonardo Lareo, Raúl A. Poutou, Ángela C. Sosa, Luis A. Barrera, .

Palabras clave: mucopolisacaridosis II, iduronato sulfatasa, estructura terciaria de proteína, metodologías computacionales

Resumen

Introducción. El síndrome de Hunter o mucopolisacaridosis tipo II (MC KUSIK 309900) es causado por la deficiencia de la iduronato 2-sulfato sulfatasa humana (E.C. 3.1.6.13). La enzima no ha sido cristalizada y por tanto sus estructuras no se conocen por deducción experimental.
Objetivo. Proponer un modelo computacional para la estructura tridimensional de la iduronato 2-sulfato sulfatasa humana.
Materiales y métodos. Se realizó un análisis computacional de esta enzima empleando programas de libre acceso en internet como Comput pI/MW, JaMBW Chapter 3.1.7, SWISSMODEL, 3D-PSSM, ProSup. Los procesos de minimización de energía se realizaron con el programa Discover 3 del paquete Insight II (2004).
Resultados. Se propone un modelo tridimensional de la iduronato 2-sulfato sulfatasa humana que presenta 33,3% en hélice, 7,2% en hoja plegada y 59,5% en enrollamiento al azar (coil). Se hallaron valores de RMS (del inglés Root Mean Square) de 0,78 y 0,86Å al compararla con otras enzimas de la misma familia. El modelo revela cinco sitios potenciales de N-glicosilación y una entrada al bolsillo que contiene los aminoácidos que componen el sitio activo. Usando este modelo se encontró una buena correlación entre el tipo de mutaciones y la gravedad de la enfermedad en 20 pacientes analizados.
Conclusión. Los valores de RMS y la correlación genotipo-fenotipo en los pacientes analizados sugieren el modelo puede usarse para predecir ciertos aspectos del comportamiento biológico de la enzima.

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  • Homero Sáenz Instituto de Errores Innatos del Metabolismo, Facultad de Ciencias, Pontificia Universidad Javeriana, Bogotá D.C., Colombia. Unidad de Biología Celular y Microscopía, Decanato de Medicina, Universidad Centroccidental “Lisandro Alvarado”, Barquisi
  • Leonardo Lareo Grupo de Investigación en Bioquímica Computacional, Facultad de Ciencias, Pontificia Universidad Javeriana, Bogotá D.C., Colombia.
  • Raúl A. Poutou Instituto de Errores Innatos del Metabolismo, Facultad de Ciencias, Pontificia Universidad Javeriana, Bogotá D.C., Colombia. Grupo de Biotecnología Ambiental e Industrial, Facultad de Ciencias, Pontificia Universidad Javeriana. Bogotá D.C., Colombia
  • Ángela C. Sosa Instituto de Errores Innatos del Metabolismo, Facultad de Ciencias, Pontificia Universidad Javeriana, Bogotá D.C., Colombia.
  • Luis A. Barrera Instituto de Errores Innatos del Metabolismo, Facultad de Ciencias, Pontificia Universidad Javeriana, Bogotá D.C., Colombia.

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Cómo citar
Sáenz, H., Lareo, L., Poutou, R. A., Sosa, Ángela C., & Barrera, L. A. (2007). Predicción computacional de la estructura terciaria de la iduronato 2-sulfato sulfatasa humana. Biomédica, 27(1), 7-20. https://doi.org/10.7705/biomedica.v27i1.229
Publicado
2007-03-01
Sección
Artículos originales