Identification of the NADP<sup>+</sup> Structural Binding Site and Coenzyme Effect on the Fused G6PD::6PGL Protein from <i>Giardia lamblia</i>
2019
Laura Morales-Luna | Abigail González-Valdez | Yudibeth Sixto-López | José Correa-Basurto | Beatriz Hernández-Ochoa | Noemí Cárdenas-Rodríguez | Rosa Angélica Castillo-Rodríguez | Daniel Ortega-Cuellar | Roberto Arreguin-Espinosa | Verónica Pérez de la Cruz | Hugo Serrano-Posada | Sara Centeno-Leija | Luz María Rocha-Ramírez | Edgar Sierra-Palacios | Alba Mónica Montiel-González | Yadira Rufino-González | Jaime Marcial-Quino | Saúl Gómez-Manzo
<i>Giardia lambia</i> is a flagellated protozoan parasite that lives in the small intestine and is the causal agent of giardiasis. It has been reported that <i>G. lamblia</i> exhibits glucose-6-phosphate dehydrogenase (G6PD), the first enzyme in the pentose phosphate pathway (PPP). Our group work demonstrated that the <i>g6pd</i> and <i>6pgl</i> genes are present in the open frame that gives rise to the fused G6PD::6PGL protein; where the G6PD region is similar to the 3D structure of G6PD in <i>Homo sapiens</i>. The objective of the present work was to show the presence of the structural NADP<sup>+</sup> binding site on the fused G6PD::6PGL protein and evaluate the effect of the NADP<sup>+</sup> molecule on protein stability using biochemical and computational analysis. A protective effect was observed on the thermal inactivation, thermal stability, and trypsin digestions assays when the protein was incubated with NADP<sup>+</sup>. By molecular docking, we determined the possible structural-NADP<sup>+</sup> binding site, which is located between the Rossmann fold of G6PD and 6PGL. Finally, molecular dynamic (MD) simulation was used to test the stability of this complex; it was determined that the presence of both NADP<sup>+</sup> structural and cofactor increased the stability of the enzyme, which is in agreement with our experimental results.
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