Giardia intestinalis arginine deiminase (ADI) is an important arginine metabolic enzyme involved in the energy production and defense in this protozoan and its absence in the human host makes ADI is an attractive target for drug design against G. intestinalis. However, the crystallographic structure of G. intestinalis ADI remains unresolved. Because of its relevance, in this work we generated a theoretical model for the ADI homodimer structure of G. intestinalis using computational technique homology modeling. The sequence alignment, secondary and three-dimensional structure generated shows amino acid conservation at the active site compared with ADI in other organisms. Also, in proposing possible active-site inhibitors, a set of 3196 commercial and 19 in-house benzimidazole derivatives were docked into the active site cavity. Molecular dynamics were carried out to evaluate the stability of the dimer enzyme and the ligand-enzyme complexes. The results allowed the identification of molecules with theoretically high affinities for the catalytic site, also enabling the most relevant interactions that promote stabilization in it. These results constitute valuable information for the design and optimization of selective inhibitors.

Homology modeling of Giardia intestinalis arginine deiminase: Insights into its structure and inhibition

248th National Meeting (2014)

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