Biomaterial Database

Copper-zinc superoxide dismutase: theoretical insights into the catalytic mechanism. 2005

Vladimir Pelmenschikov, and Per E M Siegbahn

Department of Physics, Stockholm University, S-106 91 Stockholm, Sweden. vovan@physto.se

The mechanism for the toxic superoxide radical disproportionation to molecular oxygen and hydrogen peroxide by copper-zinc superoxide dismutase (CuZnSOD) has been studied using the B3LYP hybrid density functional. On the basis of the X-ray structure of the enzyme, the molecular system investigated includes the first-shell protein ligands of the two metal centers as well as the second-shell ligand Asp122. The substrates of the model reaction are two superoxide radical anions, approaching the copper center at the beginning of two half-reactions: the first part of the catalytic cycle involving Cu+ oxidation and the second part reducing Cu2+ back to its initial state. The quantitative free energy profile of the reaction is obtained and discussed in connection with the experimental data on the reduction potentials and CuZnSOD kinetics. The optimized structures are analyzed and compared to the experimental ones. The two transition states alternate the protonation state of His61 and correspond to histidine Cu-His61-Zn bridge rupture/reformation. Modifications applied to the initial model allow the importance of Asp122 for catalysis to be estimated.

UI	MeSH Term	Description	Entries
D008962	Models, Theoretical	Theoretical representations that simulate the behavior or activity of systems, processes, or phenomena. They include the use of mathematical equations, computers, and other electronic equipment.	Experimental Model,Experimental Models,Mathematical Model,Model, Experimental,Models (Theoretical),Models, Experimental,Models, Theoretic,Theoretical Study,Mathematical Models,Model (Theoretical),Model, Mathematical,Model, Theoretical,Models, Mathematical,Studies, Theoretical,Study, Theoretical,Theoretical Model,Theoretical Models,Theoretical Studies
D008968	Molecular Conformation	The characteristic three-dimensional shape of a molecule.	Molecular Configuration,3D Molecular Structure,Configuration, Molecular,Molecular Structure, Three Dimensional,Three Dimensional Molecular Structure,3D Molecular Structures,Configurations, Molecular,Conformation, Molecular,Conformations, Molecular,Molecular Configurations,Molecular Conformations,Molecular Structure, 3D,Molecular Structures, 3D,Structure, 3D Molecular,Structures, 3D Molecular
D010084	Oxidation-Reduction	A chemical reaction in which an electron is transferred from one molecule to another. The electron-donating molecule is the reducing agent or reductant; the electron-accepting molecule is the oxidizing agent or oxidant. Reducing and oxidizing agents function as conjugate reductant-oxidant pairs or redox pairs (Lehninger, Principles of Biochemistry, 1982, p471).	Redox,Oxidation Reduction
D002384	Catalysis	The facilitation of a chemical reaction by material (catalyst) that is not consumed by the reaction.	Catalyses
D003300	Copper	A heavy metal trace element with the atomic symbol Cu, atomic number 29, and atomic weight 63.55.	Copper-63,Copper 63
D006639	Histidine	An essential amino acid that is required for the production of HISTAMINE.	Histidine, L-isomer,L-Histidine,Histidine, L isomer,L-isomer Histidine
D000465	Algorithms	A procedure consisting of a sequence of algebraic formulas and/or logical steps to calculate or determine a given task.	Algorithm
D013482	Superoxide Dismutase	An oxidoreductase that catalyzes the reaction between SUPEROXIDES and hydrogen to yield molecular oxygen and hydrogen peroxide. The enzyme protects the cell against dangerous levels of superoxide.	Hemocuprein,Ag-Zn Superoxide Dismutase,Cobalt Superoxide Dismutase,Cu-Superoxide Dismutase,Erythrocuprein,Fe-Superoxide Dismutase,Fe-Zn Superoxide Dismutase,Iron Superoxide Dismutase,Manganese Superoxide Dismutase,Mn-SOD,Mn-Superoxide Dismutase,Ag Zn Superoxide Dismutase,Cu Superoxide Dismutase,Dismutase, Ag-Zn Superoxide,Dismutase, Cobalt Superoxide,Dismutase, Cu-Superoxide,Dismutase, Fe-Superoxide,Dismutase, Fe-Zn Superoxide,Dismutase, Iron Superoxide,Dismutase, Manganese Superoxide,Dismutase, Mn-Superoxide,Dismutase, Superoxide,Fe Superoxide Dismutase,Fe Zn Superoxide Dismutase,Mn SOD,Mn Superoxide Dismutase,Superoxide Dismutase, Ag-Zn,Superoxide Dismutase, Cobalt,Superoxide Dismutase, Fe-Zn,Superoxide Dismutase, Iron,Superoxide Dismutase, Manganese
D013816	Thermodynamics	A rigorously mathematical analysis of energy relationships (heat, work, temperature, and equilibrium). It describes systems whose states are determined by thermal parameters, such as temperature, in addition to mechanical and electromagnetic parameters. (From Hawley's Condensed Chemical Dictionary, 12th ed)	Thermodynamic
D015032	Zinc	A metallic element of atomic number 30 and atomic weight 65.38. It is a necessary trace element in the diet, forming an essential part of many enzymes, and playing an important role in protein synthesis and in cell division. Zinc deficiency is associated with ANEMIA, short stature, HYPOGONADISM, impaired WOUND HEALING, and geophagia. It is known by the symbol Zn.