title: Inhibition of ferric ion to oxalate oxidase shed light on the substrate binding site.
abstract: Oxalate oxidase (OxOx), a well known enzyme catalyzes the cleavage of oxalate to carbon dioxide with reduction of dioxygen to hydrogen peroxide, however its catalytic process is not well understood. To define the substrate binding site, interaction of Fe(3+) ions with OxOx was systemically investigated using biochemical method, circular dichrosim spectroscopy, microscale thermophoresis, and computer modeling. We demonstrated that Fe(3+) is a non-competitive inhibitor with a milder binding affinity to OxOx, and the secondary structure of the OxOx was slightly altered upon its binding. On the basis of the structural properties of the OxOx and its interaction with Fe(3+) ions, two residue clusters of OxOx were assigned as potential Fe(3+) binding sites, the mechanism of the inhibition of Fe(3+) was delineated. Importantly, the residues that interact with Fe(3+) ions are involved in the substrate orienting based on computer docking. Consequently, the interaction of OxOx with Fe(3+) highlights insight into substrate binding site in OxOx.
authors.affiliation: State Key Laboratory of Bioreactor Engineering, Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, Shanghai, 200237, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Pang
authors.affiliation: State Key Laboratory of Bioreactor Engineering, Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, Shanghai, 200237, China.
authors.forename: Wanjun
authors.initials: W
authors.lastname: Lan
authors.affiliation: State Key Laboratory of Bioreactor Engineering, Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, Shanghai, 200237, China.
authors.forename: Xuelei
authors.initials: X
authors.lastname: Huang
authors.affiliation: State Key Laboratory of Bioreactor Engineering, Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, Shanghai, 200237, China.
authors.forename: Guanke
authors.initials: G
authors.lastname: Zuo
authors.affiliation: State Key Laboratory of Bioreactor Engineering, Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, Shanghai, 200237, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Bioreactor Engineering, Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, Shanghai, 200237, China. jyzhang@ecust.edu.cn.
authors.forename: Jingyan
authors.initials: J
authors.lastname: Zhang
mesh_terms: D001665:Binding Sites; D002384:Catalysis; D002942:Circular Dichroism; D006861:Hydrogen Peroxide / Q000737:chemistry; D007477:Ions / Q000737:chemistry*; D007501:Iron / Q000737:chemistry*; D008958:Models, Molecular; D062105:Molecular Docking Simulation; D010088:Oxidoreductases / Q000037:antagonists & inhibitors / Q000737:chemistry*; D010100:Oxygen / Q000737:chemistry; D017433:Protein Structure, Secondary; D013379:Substrate Specificity
chemical_list: D007477:Ions; D006861:Hydrogen Peroxide; D007501:Iron; D010088:Oxidoreductases; C020598:oxalate oxidase; D010100:Oxygen
keywords: Computer modeling; Fe3+ ion; Inhibition; Oxalate oxidase; Substrate binding site