title: Selenium-containing 15-mer peptides with high glutathione peroxidase-like activity.
abstract: Glutathione peroxidase (GPX) is one of the most crucial antioxidant enzymes in a variety of organisms. Here we described a new strategy for generating a novel GPX mimic by combination of a phage-displayed random 15-mer peptide library followed by computer-aided rational design and chemical mutation. The novel GPX mimic is a homodimer consisting of a 15-mer selenopeptide with an appropriate catalytic center, a specific binding site for substrates, and high catalytic efficiency. Its steady state kinetics was also studied, and the values of k(cat)/K(m)(GSH) and k(cat)/ K(mH(2)O(2)) were found to be similar to that of native GPX and the highest among the existing GPX mimics. Moreover, the novel GPX mimic was confirmed to have a strong antioxidant ability to inhibit lipid peroxidation by measuring the content of malondialdehyde, cell viability, and lactate dehydrogenase activity. Importantly, the novel GPX mimic can penetrate into the cell membrane because of its small molecular size. These characteristics endue the novel mimic with potential perspective for pharmaceutical applications.
authors.affiliation: Key Laboratory for Molecular Enzymology and Engineering of the Ministry of Education, Changchun, Peoples Republic of China.
authors.forename: Ye
authors.initials: Y
authors.lastname: Sun
authors.forename: Tianyu
authors.initials: T
authors.lastname: Li
authors.forename: Hua
authors.initials: H
authors.lastname: Chen
authors.forename: Kun
authors.initials: K
authors.lastname: Zhang
authors.forename: Keyan
authors.initials: K
authors.lastname: Zheng
authors.forename: Ying
authors.initials: Y
authors.lastname: Mu
authors.forename: Ganglin
authors.initials: G
authors.lastname: Yan
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.forename: Jiacong
authors.initials: J
authors.lastname: Shen
authors.forename: Guimin
authors.initials: G
authors.lastname: Luo
mesh_terms: D000595:Amino Acid Sequence; D020134:Catalytic Domain; D005979:Glutathione Peroxidase / Q000737:chemistry / Q000378:metabolism*; D007700:Kinetics; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism*; D011487:Protein Conformation; D012643:Selenium / Q000378:metabolism*
chemical_list: D010455:Peptides; D005979:Glutathione Peroxidase; D012643:Selenium