| Autor: |
Osorio MI; Center for Bioinformatics and Integrative Biology, Facultad de Ciencias de la Vida, Universidad Andres Bello, Av. República 330, Santiago 8370146, Chile.; Centro de Investigación Biomédica, Facultad de Medicina, Universidad Diego Portales, Ejército 141, Santiago 837007, Chile., Bruna N; Center for Bioinformatics and Integrative Biology, Facultad de Ciencias de la Vida, Universidad Andres Bello, Av. República 330, Santiago 8370146, Chile., García V; Facultad de Química e Ingeniería Química, Universidad Nacional Mayor de San Marcos, Lima 15081, Peru., González-Rodríguez L; Facultad de Ingeniería y Negocios, Universidad de las Américas, Sede Concepción, Santiago 9170022, Chile., Leal MS; Center for Bioinformatics and Integrative Biology, Facultad de Ciencias de la Vida, Universidad Andres Bello, Av. República 330, Santiago 8370146, Chile., Salgado F; Center for Bioinformatics and Integrative Biology, Facultad de Ciencias de la Vida, Universidad Andres Bello, Av. República 330, Santiago 8370146, Chile., Vargas-Reyes M; Center for Bioinformatics and Integrative Biology, Facultad de Ciencias de la Vida, Universidad Andres Bello, Av. República 330, Santiago 8370146, Chile., González-Nilo F; Center for Bioinformatics and Integrative Biology, Facultad de Ciencias de la Vida, Universidad Andres Bello, Av. República 330, Santiago 8370146, Chile., Pérez-Donoso JM; Center for Bioinformatics and Integrative Biology, Facultad de Ciencias de la Vida, Universidad Andres Bello, Av. República 330, Santiago 8370146, Chile., Yáñez O; Núcleo de Investigación en Data Science, Facultad de Ingeniería y Negocios, Universidad de las Américas, Santiago 7500000, Chile. |
| Abstrakt: |
Xenobiotic reductase B (XenB) catalyzes the reduction of the aromatic ring or nitro groups of nitroaromatic compounds with methyl, amino or hydroxyl radicals. This reaction is of biotechnological interest for bioremediation, the reuse of industrial waste or the activation of prodrugs. However, the structural factors that explain the binding of XenB to different substrates are unknown. Molecular dynamics simulations and quantum mechanical calculations were performed to identify the residues involved in the formation and stabilization of the enzyme/substrate complex and to explain the use of different substrates by this enzyme. Our results show that Tyr65 and Tyr335 residues stabilize the ligands through hydrophobic interactions mediated by the aromatic rings of these aminoacids. The higher XenB activity determined with the substrates 1,3,5-trinitrobenzene and 2,4,6-trinitrotoluene is consistent with the lower energy of the highest occupied molecular orbital (LUMO) orbitals and a lower energy of the homo orbital (LUMO), which favors electrophile and nucleophilic activity, respectively. The electrostatic potential maps of these compounds suggest that the bonding requires a large hydrophobic region in the aromatic ring, which is promoted by substituents in ortho and para positions. These results are consistent with experimental data and could be used to propose point mutations that allow this enzyme to process new molecules of biotechnological interest. |
