Inorganic Chemistry 1994, 33, 83-87

One- and Two-Dimensional 1H NMR Studies of the Active Site of Iron(II) Superoxide Dismutase from Escherichia coli

Ming, L.-J.*
Department of Chemistry and Institute for Biomolecular Science
University of South Florida
Tampa, FL 33620-5250

Lynch, J. B.; Holz, R. C.; Que, L., Jr.*
Department of Chemistry
University of Minnesota
Minneapolis, MN 55455

Abstract:
The iron(II) superoxide dismutase (FeSOD) from Escherichia coli exhibits relatively sharp well-resolved paramagnetically shifted NMR signals. These signals can be associated with the endogenous ligands characterized by X-ray crystallography for the oxidized form (FeSOD). Our results demonstrate that the active site remains intact upon reduction of the Fe(III) site, retaining the same coordination modes for the three N-epsilon-coordinated His residues (presumably His-26, His-75, and His-162) and the Asp residue (presumably Asp-158). The N-H resonances of the coordinated histidines are found at 88, 43, and 37 ppm, while the signals at 24.5 (E), 19 (G), and 15 (J) ppm are assigned to the Asp residue by the observation of nuclear Overhauser effects (NOE) and bond correlations among the resonances. Distances of 1.9 and 2.4 Angstrom can be
estimated between the protons E and G and the protons E and J, respectively, attributable to the -CbH2-CaH < spin system of the Asp residue. The Asp assignments are corroborated by the observation of interresidue interactions between the CaH's of Asp-158 and Trp-160. The resonances of the latter residue are identified by NOE and scalar connectivities, the most critical assignment being the NaH at 22 ppm (F). According to the crystal structure of the corresponding enzyme from Psedumonas ovalis (Stoddard, B. L.; Howell, P. L.; Ringe, D.; Petsko, G. A, Biochemistry 1990, 29, 8885-8893), this proton is hydrogen-bonded to the free carboxylate oxygen of Asp-158. This interaction thus rationalizes the paramagnetic shift observed for signal F and its very slow exchange with solvent which occurs only upon long-term standing.
 
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