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Protein–Ligand Interaction Study of Cp OGA in Complex with GlcNAcstatin
Author(s) -
Sousa Paulo Robson M.,
de Alencar Nelson Alberto N.,
Lima Anderson H.,
Lameira Jerônimo,
Alves Cláudio Nahum
Publication year - 2013
Publication title -
chemical biology and drug design
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.59
H-Index - 77
eISSN - 1747-0285
pISSN - 1747-0277
DOI - 10.1111/cbdd.12078
Subject(s) - molecular mechanics , clostridium perfringens , molecular dynamics , chemistry , stereochemistry , active site , protonation , computational chemistry , biochemistry , enzyme , biology , bacteria , genetics , organic chemistry , ion
The GlcNAcstatin is a potent inhibitor of O ‐glycoprotein 2‐acetamino‐2‐deoxy‐β‐D‐glucopyranosidase, which has been related with type II diabetes and neurodegenerative disorders. Herein, hybrid quantum mechanics/molecular mechanics, molecular dynamics simulations, and potential of mean force were employed to study the interactions established between GlcNAcstatin and a bacterial O ‐GlcNAcase enzyme from Clostridium perfringens . The results reveal that the imidazole nitrogen atom of GlcNAcstatin has shown a better interaction with the active site of Clostridium perfringens in its protonated form, which is compatible with a substrate‐assisted reaction mechanism involving two conserved aspartate residues (297 and 298). Furthermore, the quantum mechanics/molecular mechanics–molecular dynamics simulations appointed a strong interaction between Asp401, Asp298, and Asp297 residues and the GlcNAcstatin inhibitor, which is in accordance with experimental data. Lastly, these results may contribute to understand the molecular mechanism of inhibition of Clostridium perfringens by GlcNAcstatin inhibitor and, consequently, this study might be useful to design new molecules with more interesting inhibitory activity.