Resumo

LAVADIE-GONZALEZ, Carlos E.; SERRAT-DIAZ, Manuel de J.  e  AZCANIO-FUENTES, Lisandra. Homology modelling and in silico Structural characterization of lanosterol 14α-demethylase from Cryptococcus neoformans var. Grubii. Rev Cub Quim [online]. 2021, vol.33, n.2, pp. 198-226.  Epub 24-Jun-2021. ISSN 2224-5421.

Cryptococcal meningitis mostly affect immunocompromised patients, whose pathogens have developed drug resistance mechanisms. Modern biotechnology has laid hands on theoretical-computational methods, since fight against these pathogens involves structural characterization of pharmacological targets. A refined homology model was built for enzyme CYP51 from Cryptococcus neoformans. Quality assessment confirmed model reliability: stereochemical analysis yielded 97,46 % of residues located in allowed regions of Ramachandran Plots; ProSA analysis placed the model within expected interval in Z-score scatter plot (Z-score = -8,34); distribution of 3D-1D correlation left 84,83 % of residues with average score ≥ 0,2. Two access tunnels towards active site were described, as well as heme cofactor inside catalytic pocket, whose interactions with surrounding residues points to a pronounced hydrophobicity of that region. Evolutionary analysis showed high conservation in residues forming the catalytic site. Computational site-directed generation of three reported point mutations allowed to gain an insight into azole-resistance mechanisms in the species.

Palavras-chave : homology modelling; Cryptococcus neoformans; CYP51; heme group.

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