“Theoretical studies of structural and functional characteristics of
Transcrição
“Theoretical studies of structural and functional characteristics of
XVI Simpósio Brasileiro de Química Teórica – SBQT 2011 Ouro Preto – MG, 20-23 Novembro de 2011 30 Anos SBQT “Theoretical studies of structural and functional characteristics of Fusarium solani β-glucosidase by molecular modeling” Nascimento Soelange B (PG), Alencar Nelson AN (PG), Sousa Robson PM(G), Pinheiro Silvana S(PG), Silva Natalia F(PG), Silva Alessandra P(G), Costa Kelly M(PG), Oliveira Renata LS (PG), Lameiro Jerônimo S (PQ), Alves Cláudio N (PQ) Universidade Federal do Pará, CP 11101, 66075-110, Belém, PA, Brasil. Key-words: Fusarium solani, β-glucosidase, Molecular docking β-glucosidase is a glycoside hydrolase 3 (GH3) and in fungi this enzyme is related with the synthesis of cell wall. Fusarium solani is pathogenic fungi responsible for disease on ~100 genera of plants and it is also associated with opportunistic fungal infections and keratitis in humans. Thus, selective inhibitors for βglucosidase appears as new strategies for suppress fungal diseases. In this study, we have used molecular modeling to predict the three dimensional structure. In addition, to explain the interaction between PUGNAc and six analogues inhibitors and β-glucosidase enzyme was analyzed in order to understand inhibition mechanism of β-glucosidase. The structure three-dimensional of βglucosidase from F. solani (FsbGlc) was predicted by molecular homology using as template code PDB 2OXN from Vibrio cholera (VcNagZ). The interaction study for FsbGlc-PUGNAc and VcNagZ-PUGNAc complexes were analyzed by molecular docking. The model was built by Modeller9v8 program and docking simulation was performed using Vina v1.5.4 program with AutoDock Tools 4.2. Our model had 25.5% sequence identity and was validated by Ramachandran plot with 86.6% of amino acid residues within regions of very favorable and RMSD of 0.5 Å. The modeled protein FsbGlc active site remained conserved and docking study showed low affinity energy and good correlation with logKI values for all PUGNAc analogues in both FsbGlc-PUGNAc and VcNagZ-PUGNAc complexes measured by the kinetic Ki data with R = 0.898 and R = 0.897 respectively. These results are promising and further studies are needed to validate the dynamic flexibility of the protein modeled. Support: UFPA, LPDF, CNPq, CAPES.