title: Redox thermodynamics of lactoperoxidase and eosinophil peroxidase.
abstract: Eosinophil peroxidase (EPO) and lactoperoxidase (LPO) are important constituents of the innate immune system of mammals. These heme enzymes belong to the peroxidase-cyclooxygenase superfamily and catalyze the oxidation of thiocyanate, bromide and nitrite to hypothiocyanate, hypobromous acid and nitrogen dioxide that are toxic for invading pathogens. In order to gain a better understanding of the observed differences in substrate specificity and oxidation capacity in relation to heme and protein structure, a comprehensive spectro-electrochemical investigation was performed. The reduction potential (E degrees ') of the Fe(III)/Fe(II) couple of EPO and LPO was determined to be -126mV and -176mV, respectively (25 degrees C, pH 7.0). Variable temperature experiments show that EPO and LPO feature different reduction thermodynamics. In particular, reduction of ferric EPO is enthalpically and entropically disfavored, whereas in LPO the entropic term, which selectively stabilizes the oxidized form, prevails on the enthalpic term that favors reduction of Fe(III). The data are discussed with respect to the architecture of the heme cavity and the substrate channel. Comparison with published data for myeloperoxidase demonstrates the effect of heme to protein linkages and heme distortion on the redox chemistry of mammalian peroxidases and in consequence on the enzymatic properties of these physiologically important oxidoreductases.
authors: Department of Chemistry, University of Modena and Reggio Emilia, via Campi 183, Modena, Italy. gianantonio.battistuzzi@unimore.it
authors: Gianantonio
authors: G
authors: Battistuzzi
authors: Marzia
authors: M
authors: Bellei
authors: Jutta
authors: J
authors: Vlasits
authors: Srijib
authors: S
authors: Banerjee
authors: Paul G
authors: PG
authors: Furtmüller
authors: Marco
authors: M
authors: Sola
authors: Christian
authors: C
authors: Obinger
mesh_terms: D000818:Animals; D002417:Cattle; D004804:Eosinophils / Q000201:enzymology*; D006801:Humans; D007501:Iron / Q000378:metabolism; D007784:Lactoperoxidase / Q000737:chemistry / Q000378:metabolism*; D008958:Models, Molecular; D010084:Oxidation-Reduction; D010544:Peroxidases / Q000737:chemistry / Q000378:metabolism*; D011487:Protein Conformation; D013056:Spectrophotometry, Ultraviolet; D013379:Substrate Specificity; D013816:Thermodynamics
chemical_list: D007501:Iron; D007784:Lactoperoxidase; D010544:Peroxidases