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Engineering the Redox Potential over a Wide Range Within a New Class of FeS Proteins

Overview
Journal J Am Chem Soc
Specialty Chemistry
Date 2010 Sep 4
PMID 20812736
Citations 26
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Abstract

MitoNEET is a newly discovered mitochondrial protein and a target of the TZD class of antidiabetes drugs. MitoNEET is homodimeric with each protomer binding a [2Fe-2S] center through a rare 3-Cys and 1-His coordination geometry. Both the fold and the coordination of the [2Fe-2S] centers suggest that it could have novel properties compared to other known [2Fe-2S] proteins. We tested the robustness of mitoNEET to mutation and the range over which the redox potential (E(M)) could be tuned. We found that the protein could tolerate an array of mutations that modified the E(M) of the [2Fe-2S] center over a range of ∼700 mV, which is the largest E(M) range engineered in an FeS protein and, importantly, spans the cellular redox range (+200 to -300 mV). These properties make mitoNEET potentially useful for both physiological studies and industrial applications as a stable, water-soluble, redox agent.

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References
1.
Dicus M, Conlan A, Nechushtai R, Jennings P, Paddock M, Britt R . Binding of histidine in the (Cys)3(His)1-coordinated [2Fe-2S] cluster of human mitoNEET. J Am Chem Soc. 2010; 132(6):2037-49. PMC: 2820139. DOI: 10.1021/ja909359g. View

2.
Kuila D, Fee J . Evidence for a redox-linked ionizable group associated with the [2Fe-2S] cluster of Thermus Rieske protein. J Biol Chem. 1986; 261(6):2768-71. View

3.
Iwasaki T, Kounosu A, Samoilova R, Dikanov S . 15N HYSCORE characterization of the fully deprotonated, reduced form of the archaeal Rieske [2Fe-2S] center. J Am Chem Soc. 2006; 128(7):2170-1. DOI: 10.1021/ja0562393. View

4.
Paddock M, Wiley S, Axelrod H, Cohen A, Roy M, Abresch E . MitoNEET is a uniquely folded 2Fe 2S outer mitochondrial membrane protein stabilized by pioglitazone. Proc Natl Acad Sci U S A. 2007; 104(36):14342-7. PMC: 1963346. DOI: 10.1073/pnas.0707189104. View

5.
Miller A . Redox tuning over almost 1 V in a structurally conserved active site: lessons from Fe-containing superoxide dismutase. Acc Chem Res. 2008; 41(4):501-10. DOI: 10.1021/ar700237u. View