title: Catalytic activity of human placental alkaline phosphatase (PLAP): insights from a computational study.
abstract: 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 for each 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.
authors.affiliation: INFIQC, CONICET and Departamento de Matemática y Física, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Ciudad Universitaria , Córdoba 5000, Argentina.
authors.forename: Gabriela L
authors.initials: GL
authors.lastname: Borosky
mesh_terms: D000469:Alkaline Phosphatase / Q000737:chemistry* / Q000378:metabolism*; D020134:Catalytic Domain; D018360:Crystallography, X-Ray; D058851:GPI-Linked Proteins / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D007527:Isoenzymes / Q000737:chemistry* / Q000378:metabolism*; D007700:Kinetics; D008958:Models, Molecular; D011789:Quantum Theory; D013379:Substrate Specificity
chemical_list: D058851:GPI-Linked Proteins; D007527:Isoenzymes; D000469:Alkaline Phosphatase; C019839:alkaline phosphatase, placental