Molecular Playground/Nickel Superoxide Dismutase

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Revision as of 21:29, 11 December 2012

Molecular Playground/Nickel Superoxide Dismutase

Nickel superoxide dismutase (NiSOD) is one of the CBI Molecules being studied in the University of Massachusetts, Amherst Chemistry-Biology Interface Program at Umass Amherst and on display at the Molecular Playground.

Introduction

Nickel Superoxide Dismutase (NiSOD) is the newest member in a class of enzymes that protects organisms from oxidative stress caused by superoxide, a harmful free radical byproduct of aerobic metabolism. NiSOD reacts with two molecules of superoxide, to form O₂ and H₂O₂ with rates occurring at or near the diffusion limit. During catalysis, the redox-active nickel center cycles between an oxidized and reduced state. This reaction is termed the pin pong mechanism and is shown below.

M^{(n + 1)} + O₂^•- → Mⁿ⁺ + O₂

Mⁿ⁺ + O₂^•- + 2H⁺ → M^{(n + 1)} + H₂O₂
—————————————————

2O₂^•- + 2H⁺ → O₂ + H₂O₂

NiSOD is unique among SOD's for a variety of reasons.
NiSOD shares no sequence homology with the other known SOD's (Fig. 1). Copper, iron, and manganese SOD are redox active in aqueous media at biological pH. Nickel does not, and requires the coordination of the two cysteine ligands to tune its redox potential, which is estimated to lie above 2 eV, far outside the biologically relevant redox potential necessary to oxidize or reduce superoxide [-160 to +879 eV]. The ligands employed in the redox-active metal center are distinct. Cu/Zn, Fe, and MnSOD employ only aspartic acids, waters, and histidines. In NiSOD, the nickel center is coordinated by the side chains of cysteine 2 and cysteine 6, as well as the N-terminal amine, the amide group of cysteine 2 and an axial histidine ligand (Fig. 1).

Fig. 1: Active site structures of the four known SOD's.

Fig. 2: Hexameric NiSOD. Figure created with PyMol. PDB ID 1T6U.