title: A novel 65-mer peptide imitates the synergism of superoxide dismutase and glutathione peroxidase.
abstract: Reactive oxygen species (ROS) are involved in cell growth, differentiation, and death. Excessive amounts of ROS (e.g., O(2)(-), H(2)O(2), and HO) play a role in aging as well as in many human diseases. Superoxide dismutase (SOD) and glutathione peroxidase (GPx) are critical antioxidant enzymes in living organisms. SOD catalyzes the dismutation of O(2)(-) to H(2)O(2), and GPx catalyzes the reduction of H(2)O(2) and other harmful peroxides by glutathione (GSH). They not only function in catalytic processes but also protect each other, resulting in more efficient removal of ROS, protection of cells against injury, and maintenance of the normal metabolism of ROS. To imitate the synergism of SOD and GPx, a 65-mer peptide (65P), containing sequences that form the domains of the active center of SOD and the catalytic triad of GPx upon the incorporation of some metals, was designed on the basis of native enzyme structural models; 65P was expressed in the cysteine auxotrophic expression system to obtain Se-65P. Se-65P was converted into Se-CuZn-65P by incorporating Cu(2+) and Zn(2+). Se-CuZn-65P exhibited high SOD and GPx activities because it has a delicate dual-activity center. The synergism of the enzyme mimic was evaluated by using an in vitro model and a xanthine/xanthine oxidase/Fe(2+)-induced mitochondrial damage model system. We anticipate that the peptide enzyme mimic with synergism is promising for the treatment of human diseases and has potential applications in medicine as a potent antioxidant.
authors.affiliation: Research Center for Analytical Instrumentation, Institute of Cyber-Systems and Control, State Key Lab of Industrial Control Technology, Zhejiang University, Hangzhou 310058, PR China.
authors.forename: Fei
authors.initials: F
authors.lastname: Yan
authors.forename: Ganglin
authors.initials: G
authors.lastname: Yan
authors.forename: Shaowu
authors.initials: S
authors.lastname: Lv
authors.forename: Na
authors.initials: N
authors.lastname: Shen
authors.forename: Ying
authors.initials: Y
authors.lastname: Mu
authors.forename: Tong
authors.initials: T
authors.lastname: Chen
authors.forename: Pingsheng
authors.initials: P
authors.lastname: Gong
authors.forename: Yawei
authors.initials: Y
authors.lastname: Xu
authors.forename: Limin
authors.initials: L
authors.lastname: Lv
authors.forename: Junqiu
authors.initials: J
authors.lastname: Liu
authors.forename: Jiacong
authors.initials: J
authors.lastname: Shen
authors.forename: Guimin
authors.initials: G
authors.lastname: Luo
mesh_terms: D020134:Catalytic Domain; D002942:Circular Dichroism; D005979:Glutathione Peroxidase / Q000737:chemistry / Q000378:metabolism*; D008928:Mitochondria / Q000378:metabolism; D008958:Models, Molecular; D018716:Molecular Mimicry; D010455:Peptides / Q000737:chemistry* / Q000378:metabolism; D011487:Protein Conformation; D017382:Reactive Oxygen Species / Q000378:metabolism; D013482:Superoxide Dismutase / Q000737:chemistry / Q000378:metabolism*
chemical_list: D010455:Peptides; D017382:Reactive Oxygen Species; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase