Protein Control of Redox Potentials of Iron−Sulfur Proteins

Stephens, Philip J.; Jollie, David; Warshel, Arieh

doi:10.1021/cr950045w

Cited by 350 publications

(380 citation statements)

References 93 publications

Supporting

Mentioning

360

Contrasting

Unclassified

Order By: Relevance

“…Ferredoxins that contain [4Fe4S] clusters generally use the 2ϩ͞1ϩ couple; HiPiP iron proteins instead shuttle between the 3ϩ͞2ϩ forms. The electrochemical couple we observe on the DNA electrodes is in fact in the range found typically for the 3ϩ͞2ϩ couple of [4Fe4S] clusters of HiPiP proteins (67)(68)(69)(70)(71)(72)(73)(74). Although redox studies of Endo III suggested that reduction of the [4Fe4S] 2ϩ must occur at potentials ϽϪ600 mV versus NHE and oxidation could not be accomplished without decomposition (2,38), these studies were conducted in the absence of DNA, where the FCL is accessible to solvent.…”

Section: Redox Properties Of Muty and Hipip Iron Proteinsmentioning

confidence: 64%

“…Because [4Fe4S] cluster potentials are well known to be extremely sensitive to environment beyond the ligating atoms, it is reasonable that binding of the DNA polyanion would alter the potential (67)(68)(69)(70)(71)(72)(73)(74). Both biochemical and recent structural studies indicate that the FCL resides along the DNA-bound interface (9,30,38,75,76).…”

Section: Redox Properties Of Muty and Hipip Iron Proteinsmentioning

confidence: 99%

“…Electrostatic arguments would suggest that binding of the DNA polyanion would stabilize an oxidized form of the cluster. It is also noteworthy that the many aromatic residues surrounding the cluster in MutY (1) are typically found in HiPiP proteins (69)(70)(71)(72)(73)(74); DNA binding would be expected to further shield the cluster from solution and associated oxidative decomposition in the 3ϩ form. The change in potential on histidine ligation is also consistent with a neutral nitrogen donor stabilizing Fe(II); variations in potential of similar magnitude have been observed in ferredoxin mutants where the coordinating residue is changed (77).…”

Section: Redox Properties Of Muty and Hipip Iron Proteinsmentioning

confidence: 99%

See 2 more Smart Citations

DNA-mediated charge transport for DNA repair

Boon

Livingston

Chmiel

et al. 2003

Proc. Natl. Acad. Sci. U.S.A.

223

View full text Add to dashboard Cite

MutY, like many DNA base excision repair enzymes, contains a [4Fe4S] 2؉ cluster of undetermined function. Electrochemical studies of MutY bound to a DNA-modified gold electrode demonstrate that the [4Fe4S] cluster of MutY can be accessed in a DNA-mediated redox reaction. Although not detectable without DNA, the redox potential of DNA-bound MutY is Ϸ275 mV versus NHE, which is characteristic of HiPiP iron proteins. Binding to DNA is thus associated with a change in [4Fe4S] 3؉/2؉ potential, activating the cluster toward oxidation. Given that DNA charge transport chemistry is exquisitely sensitive to perturbations in base pair structure, such as mismatches, we propose that this redox process of MutY bound to DNA exploits DNA charge transport and provides a DNA signaling mechanism to scan for mismatches and lesions in vivo.D NA repair proteins that contain a FeS redox cofactor are ubiquitous (1-7), yet a role for these factors has been lacking. Two examples, highly homologous (8), are MutY (1) and endonuclease III (Endo III) (2, 9), base excision repair enzymes from Escherichia coli (10). MutY, containing 350 residues, acts as a glycosylase to remove adenine from G:A (11-13) and 7,8-dihydro-8-oxo-2-deoxyguanonsine:A mismatches (14-21); Endo III removes pyrimidines damaged by ring saturation, contraction, or fragmentation (22-29). Although MutY and Endo III have dramatically different substrate recognition features, they both contain a [4Fe4S] 2ϩ cluster (1, 2, 9) within a Cys-X 6 -Cys-X 2 -Cys-X 5 -Cys loop located near the protein C terminus (1, 9, 30). Based on sequence alignment, a loop defined by the first two ligating cysteines, called the FCL, is proposed to be a common element of DNA repair proteins (30), present throughout phylogeny (31-37). The function, if any, for these clusters remains undetermined, although the FCL has been proposed as a structural element, aiding in DNA binding (9,30,38). Interestingly, however, MutY is capable of folding without the cluster; the [4Fe4S] 2ϩ cluster adds no stability to the enzyme, but it is critical for substrate binding and catalysis (39). The solvent-accessible [4Fe4S] 2ϩ cluster of Endo III undergoes decomposition with ferricyanide and is resistant to reduction, with an estimated midpoint potential of ϽϪ600 mV for the [4Fe4S] 2ϩ/1ϩ couple (2, 38).Here, we consider whether the [4Fe4S] 2ϩ cluster in MutY can function in DNA-mediated charge transport (CT). Many laboratories have probed DNA-mediated CT chemistry (40-42). Using biochemical, spectroscopic, and electrochemical methods, we have shown that CT through DNA can proceed over long molecular distances in a reaction that is remarkably sensitive to intervening dynamical base pair structure (43-50). DNAmediated CT has been shown to yield oxidative DNA damage from a distance within nucleosome core particles (47) and HeLa cell nuclei (51). DNA binding proteins and peptides have also been shown to modulate and participate in long-range CT chemistry (48, 49), raising the question of the physiological relevance of DNA CT....

show abstract

Section: Redox Properties Of Muty and Hipip Iron Proteinsmentioning

confidence: 64%

Section: Redox Properties Of Muty and Hipip Iron Proteinsmentioning

confidence: 99%

Section: Redox Properties Of Muty and Hipip Iron Proteinsmentioning

confidence: 99%

See 1 more Smart Citation

DNA-mediated charge transport for DNA repair

Boon

Livingston

Chmiel

et al. 2003

Proc. Natl. Acad. Sci. U.S.A.

223

View full text Add to dashboard Cite

show abstract

“…. S hydrogen bonds in influencing the redox potentials of Fe-S proteins has been actively debated in the literature (56,57). This study has determined the precise geometries of such bonds at high resolution in a neutron diffraction investigation.…”

Section: Resultsmentioning

confidence: 99%

Neutron crystallographic study on rubredoxin from Pyrococcus furiosus by BIX-3, a single-crystal diffractometer for biomacromolecules

Kurihara

Tanaka

Chatake

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

show abstract

“…The protein matrix can alter the redox potential through the ligand field produced by the chelating residues and the electrostatic potential surrounding the metal center. Such structural considerations include protein hydrogen bonding to the iron center, solvent accessibility to the site, and the number of charged residues (Stephens et al, 1996) in the presence of 1 equivalent of Cd(I1) (closed circles). The spectra were recorded at 25 "C in a 2 mm pathlength cell with a protein concentration of 10 y M in 1 mM MOPS containing 100 y M tricarhoxyethylephosphine at pH 8. in the presence of 1 equivalent Cd(I1) (closed circles).…”

Section: Effect Of Metal-binding On Protein Structure and Stabilitymentioning

confidence: 99%

The de novo design of a rubredoxin‐like fe site

Farinas

Regan

1998

Protein Science

View full text Add to dashboard Cite

A redox center similar to that of rubredoxin was designed into the 56 amino acid immunoglobulin binding B 1 domain of Streptococcals protein G. The redox center in rubredoxin contains an iron ion tetrahedrally coordinated by four cysteine residues, [ F e ( S -c~s )~] ",-'. The design criteria for the target site included taking backbone movements into account, tetrahedral metal-binding, and maintaining the structure and stability of the wild-type protein. The optical absorption spectrum of the Co(I1) complex of the metal-binding variant is characteristic of tetrahedral chelation by four cysteine residues. Circular dichroism and nuclear magnetic resonance measurements reveal that the metal-free and Cd(I1)-bound forms of the variant are folded correctly and are stable. The Fe(II1) complex of the metal-binding mutant reproduces the optical and the electron paramagnetic resonance spectra of oxidized rubredoxin. This demonstrates that the engineered protein chelates Fe(II1) in a tetrahedral array, and the resulting center is similar to that of oxidized rubredoxin.Keywords: de novo design; metalloprotein; protein engineering; rubredoxin Protein engineering and de novo design approaches have begun to afford a more detailed understanding of the balance of the forces that determine protein structure and function (Regan & DeGrado, 1988;Regan, 1993;Bryson et al., 1995;Regan, 1995;Dalal et al., 1997;Smith & Regan, 1997;Hellinga, 1998). To date, there are just a few examples of designed proteins that adopt a specified fold, and number which display novel activities is still smaller (Dill, 1990; Schafmeister et al., 1993;Jackson et al., 1994;Quinn et al., 1994;Yan & Erickson, 1994;Baltzer et al., 1996;Dahiyat & Mayo, 1997;Hill & DeGrado, 1998;QuCnCneur et al., 1998). A particular focus of functional design efforts has been the engineering of novel metal-binding sites. Metal-binding sites represent an attractive target because they play a variety of functions from stabilization of protein structure to catalytic roles such as the activation of water for nucleophilic attack, electron transfer, and redox activity. More recently, several groups have focused strongly on the design of metal-binding sites with particular activities in mind. For example, two metal-binding histidine residues have been engineered into rat trypsin to "switch" the catalytic activity on or off by disrupting the catalytic triad. The protein can be turned off by Cu(I1) chelation in the designed site and reactivated upon removal of Cu(I1) with EDTA (Halfon & Craik, 1996). In another design, a metal-binding site, based on the metal center of carbonic

show abstract

Protein Control of Redox Potentials of Iron−Sulfur Proteins

Cited by 350 publications

References 93 publications

DNA-mediated charge transport for DNA repair

DNA-mediated charge transport for DNA repair

Neutron crystallographic study on rubredoxin from Pyrococcus furiosus by BIX-3, a single-crystal diffractometer for biomacromolecules

The de novo design of a rubredoxin‐like fe site

Contact Info

Product

Resources

About