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Title: Spectroscopic studies on the binuclear iron center of uteroferrin
Authors: Doi, Kei
Keywords: Biophysics.
Issue Date: 1988
Publisher: ProQuest Dissertations & Theses
Citation: Source: Dissertation Abstracts International, Volume: 50-02, Section: B, page: 4140.;Advisors: Philip Aisen.
Abstract: Uteroferrin is a single-chain, mannose-rich glycoprotein of molecular weight near 36,000, isolated from the uterine secretions of pregnant or pseudopregnant (hormone-treated) sows. Its two iron atoms comprise a spin-coupled and redox active binuclear iron center. This center can exist in two stable interconvertible states: pink, reduced, EPR-visible and enzymically active, with an antiferromagnetically exchanged Fe(II)-Fe(III) cluster, and purple, oxidized, EPR-silent and inert, with the binuclear pair as Fe(III)-Fe(III). A transient intermediate species has also been identified. Engendered by the interaction of phosphate with the pink form of uteroferrin, this intermediate is purple, enzymically active, EPR-silent and devoid of the contact-shifted proton resonances seen in its pink parent. Nevertheless, it is paramagnetic, with an Fe(II)-Fe(III) couple demonstrable by Mossbauer spectroscopy. Unable to identify this intermediate by conventional EPR techniques, we turned to molybdate, a structural analog of phosphate and also an inhibitor of uteroferrin. Unlike phosphate, molybdate leaves the protein tractable to paramagnetic resonance spectroscopies. With both electron spin echo envelope modulation (ESEEM) and electron nuclear double resonance (ENDOR) spectroscopies, a superhyperfine interaction of ({dollar}\sp{lcub}95{rcub}{dollar}Mo) molybdate with the S = 1/2 center of uteroferrin was observed. This indicates that a single, monomeric species of molybdate is close to, and likely a ligand of, the binuclear cluster.;Apart from its enzymic activity and interaction with inhibitors, the biological role of uteroferrin remains less clear. Based on our EPR experiments, the function of uteroferrin does not seem to involve the direct transfer of its iron to fetal transferrin, as otherwise suggested. Instead, it is intriguing to consider whether its ability to promote Fenton chemistry, coupled with its targeting to the mannose receptors of reticulo-endothelial cells, is exploited by the scavenging macrophage in vivo.;Although considerable progress toward characterizing the properties of uteroferrin has been achieved in recent years, enigmas persist. The identity of the ligands of each iron atom and how these changes in nature or arrangement during redox transitions is still unknown. Perhaps most interestingly, the mechanism of enzymic activity, and the relation of the redox and enzymatic properties of uteroferrin to its yet uncertain physiological role, remains to be established.
Appears in Collections:Albert Einstein College of Medicine: Doctoral Dissertations

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