Homology modelling and in silico Structural characterization of lanosterol 14α-demethylase from Cryptococcus neoformans var. Grubii
Palabras clave:
modelación por homología, Cryptococcus neoformans, CYP51, grupo hemoResumen
La meningoencefalitis criptocócica afecta principalmente a pacientes inmunodeprimidos; sus patógenos han desarrollado mecanismos de resistencia a fármacos. La biotecnología moderna combate estos patógenos, empleando métodos teórico-computacionales para la caracterización estructural de dianas farmacológicas. Se obtuvo un modelo por homología refinado, de buena calidad, para la CYP51 de Cryptococcus neoformans; el diagrama de Ramachandran mostró al 97.46% de los residuos en regiones permitidas; ProSA ubicó al modelo en el intervalo esperado del Z-score (Z-score = -8,34); en la distribución de la correlación 3D-1D, 84,83 % de los residuos alcanzan puntuaje promedio ≥ 0,2. Se describieron dos túneles conducentes al sitio activo; las interacciones del cofactor hemo con residuos circundantes, en el bolsillo catalítico, indican una pronunciada hidrofobicidad de esa región. El análisis evolutivo mostró alta conservación en residuos conformantes del sitio catalítico. La generación computacional de tres sustituciones aminoacídicas reportadas permitió profundizar en los mecanismos de resistencia a azoles en la especie.
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