Alkane oxidation by polynuclear non-haem iron complexes—an imidazole effect

Fontecave, Marc; Roy, Béatrice; Lambeaux, Claude

doi:10.1039/c39910000939

Cited by 16 publications

(3 citation statements)

References 10 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, given the incapacity of reduced flavins alone to transfer electrons to the Fe(1II) center, fraction b is supposed to participate in this transfer 1131. The function of superoxide dismutase is to protect the complete system from toxic oxygen radicals derived from the autoxidation of reduced flavins [17]. The tyrosyl radical can also be generated from apoR2, lacking both the metal center and the radical, by the addition of ferrous iron in the presence of oxygen (Scheme 1)…”

mentioning

confidence: 99%

Enzymic and Chemical Reduction of the Iron Center of the Escherichia coli Ribonucleotide Reductase Protein R2

Covès

Delon

Climent

et al. 1995

European Journal of Biochemistry

Self Cite

View full text Add to dashboard Cite

The active form of protein R2, the small subunit of ribonucleotide reductase, contains a diferric center and a free radical localized at Tyrl22. Hydroxyurea scavenges this radical but leaves the iron center intact. The resulting metR2 protein is inactive. The introduction of a radical into metR2 is dependent on the reduction of the iron center. In Escherichiu coli, this is achieved by an enzyme system consisting of a NAD(P)H:flavin oxidoreductase and a poorly defined protein fraction, fraction b. Assuming that the iron center is deeply buried within the protein, electron transfer is suggested to occur over long distances. Site-directed mutngenesis allowed us to identify two invariant residues, Tyr356 at the C-terminal part of the protein and Tyr122 located 0.5 nm away from the closest iron atom, as mediators of this electron transfer. We also found that deazaflavins were excellent catalysts in the photoreduction of the iron center of metR2 and generation of the tyrosyl radical, providing the simplest and most efficient model for the physiological flavin reductase/fraction b activating system. The properties of the model reaction are described.Keywords: ribonucleotide reductase ; iron center; tyrosyl radical ; long-range electron transfer; deazaflavin.Ribonucleotide reductase is a key enzyme for all living organisms. It provides the deoxyribonucleotides required for DNA synthesis [I, 21. The enzyme from Esclzerichiu coli contains two homodimeric proteins, named protein R1 and protein R2, which have been recently crystallized and structurally characterized [3-51. Protein R I , the large component, is the site of ribonucleotide binding and reduction. Each polypeptide chain of protein R2, the small component, contains a dinuclear non-heme iron center, in which the Fe(II1) ions are antiferromagnetically coupled by a p-0x0 bridge, and an essential stable radical located on Tyrl22, adjacent to the diferric center [ 6 ] . The function of the tyrosyl radical is to generate a thiyl radical on protein R I , which in turn will activate the substrate by abstracting the 3'-hydrogen of the ribose moiety [7]. However, given that the sub-. strate binds exclusively to the R1 protein and that the tyrosyl radical in R2 is buried in the interior of the protein, inacessible to solvent, as suggested from the three-dimensional structure, a long-range electron transfer mechanism between the Rl/substrate site and R2 was proposed 14, 5 , 81.Protein R2 may also receive electrons from a variety of other reducing systems. The redox potential of the tyrosine radical/ tyrosine couple is suspected to be 0.6-0.9 V, much larger than that of the Fe(III)/Fe(II) couple, which is about -0.2 V [9]. It is thus possible to reduce selectively the radical, for example with synthetic radical scavengers such as hydroxyurea and hydroxamic acids 110-221. Hydroxyurea, an inhibitor of ribonucleotide reductase and DNA synthesis, is used as an anticancer agent in clinics. The product of the reaction ic the inactive radical-free and iron-containing form, named met...

show abstract

mentioning

confidence: 99%

Enzymic and Chemical Reduction of the Iron Center of the Escherichia coli Ribonucleotide Reductase Protein R2

Covès

Delon

Climent

et al. 1995

European Journal of Biochemistry

Self Cite

View full text Add to dashboard Cite

show abstract

“…This point is illustrated by a series of hydrocarbon oxidations with TBHP catalyzed by diferric complexes in which the ancillary ligands vary. 37,38 The results of this study are summarized in Table III-2. Table III In an earlier work 37 it was found that a Type I complex, [Fe 2 OCl 6 ](NEt 4 ) 2 , is inactive toward oxidation of cyclohexane.…”

Section: Ancillary Ligand Effectsmentioning

confidence: 96%

“…37,38 The results of this study are summarized in Table III-2. Table III In an earlier work 37 it was found that a Type I complex, [Fe 2 OCl 6 ](NEt 4 ) 2 , is inactive toward oxidation of cyclohexane. However, [Fe 2 0(H 2 0) 2 (phen) 4 ](C10 4 ) 4 , Type I-b, X = H 2 0 (Fig.…”

Section: Ancillary Ligand Effectsmentioning

confidence: 96%