title: Reinvestigation of a selenopeptide with purportedly high glutathione peroxidase activity.
abstract: A 15-amino acid long selenopeptide (15SeP) was recently reported to possess nearly the same catalytic activity as glutathione peroxidase (Gpx) for the reduction of hydrogen peroxide by glutathione (Sun, Y., Li, T. Y., Chen, H., Zhang, K., Zheng, K. Y., Mu, Y., Yan, G. L., Li, W., Shen, J. C., and Luo, G. M. (2004) J. Biol. Chem. 279, 37235-37240). Such a finding is startling considering the high efficiency of the natural enzyme and the modest catalytic properties of most short peptides. As 15SeP had been subjected only to limited chemical characterization, we prepared it by a new route involving selenocysteine-mediated native chemical ligation. High resolution matrix-assisted laser desorption ionization mass spectrometry confirmed the identity of the reaction product, whereas circular dichroism spectroscopy showed that 15SeP assumes a random coil conformation in solution. Although low levels of peroxidase activity were detectable under standard assay conditions, the peptide is >5 orders of magnitude less active than native Gpx. Our observations are incompatible with claims ascribing remarkable catalytic properties to 15SeP and suggest that the efficiency of Gpx derives from its well defined three-dimensional structure.
authors.affiliation: Laboratorium für Organische Chemie, ETH Zürich, Hönggerberg HCI F 339, CH-8093 Zürich, Switzerland.
authors.forename: Giulio
authors.initials: G
authors.lastname: Casi
authors.forename: Donald
authors.initials: D
authors.lastname: Hilvert
mesh_terms: D000818:Animals; D002384:Catalysis; D002417:Cattle; D004912:Erythrocytes / Q000201:enzymology*; D005979:Glutathione Peroxidase / Q000737:chemistry*; D010455:Peptides / Q000737:chemistry*; D017433:Protein Structure, Secondary; D012441:Saccharomyces cerevisiae / Q000201:enzymology*; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry*; D017279:Selenocysteine / Q000737:chemistry*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
chemical_list: D010455:Peptides; D029701:Saccharomyces cerevisiae Proteins; D017279:Selenocysteine; D005979:Glutathione Peroxidase