Catalytic Activity of Human Placental Alkaline Phosphatase (PLAP):Insights from a Computational Study

• Autores: Borosky, Gabriela Leonor
• Año de publicación: 2014
• Idioma: inglés
• Tipo de recurso: artículo
• Materia: Computational Chemistry; Enzymatic Catalysis; Density Functional Theory; Metalloproteins
• Institución: Consejo Nacional de Investigaciones Científicas y Técnicas

Alkaline phosphatases (APs) catalyze the hydrolysis and transphosphorylation of phosphate monoesters. Quantum-mechanical computational methods were employed to study the catalytic mechanism of human placental AP (PLAP). An active-site model was used, constructed on the basis of the X-ray crystal structure of the enzyme. Kinetic and thermodynamic evaluations were achieved foreach reaction step. Calculations shed light on the mechanistic differences that had been experimentally observed between aryl and alkyl phosphates, particularly regarding the rate-determining step. The functional implications of relevant residues in the active site were examined. The present theoretical study rationalizes experimental observations previously reported in the literature.
Fil: Borosky, Gabriela Leonor. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Físico-química de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Instituto de Investigaciones en Físico-química de Córdoba; Argentina