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Showing 1 to 20 of 46 for “"4Fe-4S"”.
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Investigating pathogen 4Fe-4S protein targets and cancer chemotherapies with bisphosphonate/diphosphate inhibitors
The broad, long-term objective of this research is to develop drug leads for new antibiotics, antiparasitics, and cancer chemotherapeutics. Two main areas of focus are inhibition of the Methyl Erythritol Phosphate (MEP; non-mevalonate pathway) pathway in bacterial and parasitic human pathogens and …
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Mechanisms of action and inhibition of [4Fe-4S] proteins IspG and IspH in isoprenoid biosynthesis
… these two enzymes. These two enzymes both are [4Fe-4S] proteins with one unique iron not bonded to any cysteine residue, and catalyze 2e-/2H+ reductions. In this study, bioorganometallic mechanisms are proposed for IspG and IspH catalyses, where direct iron-carbon interactions play important …
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Biochemical characterization of a novel iron-sulfur flavoprotein from Methanosarcina thermophila strain TM-1
… analyses indicated that Isf contained one 4Fe-4S cluster and one FMN per monomer. The midpoint potentials of the [4Fe-4S]2+/1+ center and FMN/FMNH2 redox couple were -394 and -277 mV respectively. The deduced amino acid sequence of Isf revealed high identity with Isf homologues from the CO2 …
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Molecular biology and biochemical characterization of the CO dehydrogenase-linked ferredoxin from Methanosarcina thermophila strain TM-1
… indicated that the ferredoxin contained two [4Fe-4S] clusters per monomer of 6,790 Da, although a [3Fe-4S] species was also detected in the oxidized protein. The midpoint potentials of the [4Fe-4S] and [3Fe~4S] clusters at pH 7 were -407 m V and + 103 m V, respectively. Evidence from …
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Strukturelle Untersuchungen an dem Radikalenzym (R)-2-Hydroxyisocaproyl-CoA-Dehydratase
… aktiviert werden, indem ein Aktivator, der ein [4Fe-4S]-Zentrum enthält, unter ATP-Hydrolyse ein Elektron auf die Dehydratase überträgt. Für den Aktivator werden im Laufe des Aktivierungsprozesses Nukleotid- und redox-abhängige Konformationsänderungen angenommen. Das hoch reaktive Elektron wird …
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Designing Novel Blue Copper and Purple CuA Centers in Azurin With Natural and Unnatural Amino Acids
… iron binding studies indicate the assembly of a 4Fe-4S or a 2Fe-2S iron sulfur cluster.
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The roles of redox active cofactors in catalysis : structural studies of iron sulfur cluster and flavin dependent enzymes
… flavin adenine dinucleotide (FAD) and [4Fe-4S] clusters, were originally determined to aid in electron transfer and redox chemistry. However, additional activities for these cofactors continue to be discovered. The study of FAD in the context of rebeccamycin and staurosporine …
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The metabolism of iron-sulfur clusters during hydrogen peroxide stress in escherichia coli
… isomerase. This enzyme belongs to a family of [4Fe-4S] dehydratases that are notoriously sensitive to univalent oxidation, and experiments confirmed that other members were also inactivated. In vitro and in vivo analyses showed that H2O2 directly oxidizes their solvent-exposed clusters in a …
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Superoxide stress in Escherichia coli
… O2- that has been identified is a subfamily of [4Fe-4S] dehydratases. The inactivation of those dehydratases can only explain part of its toxic effects, which implies the existence of other unknown cellular targets. We have recently identified a new class of cellular targets of O2-: non-redox …
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Mechanism, inhibition and spectroscopy of isoprenoid biosynthesis enzymes
… pyrophosphate (DMAPP). IspG and IspH are both 4Fe-4S cluster-containing proteins with a unique iron whose ligand is not a cysteine residue. Continuous-wave and pulsed electron paramagnetic resonance (EPR) experiments, with the help of isotope-labeled substrates, revealed the electronic …
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Structure and function of the terpene biosynthesis enzyme, IspH
… arrangement of the aromatic residues near the 4Fe-4S cluster and the presence of N- and C-terminal extensions, and these structure features are related to the environments in which IspHs are found. These aromatic groups protect the 4Fe-4S clusters from oxidation and are also involved in …
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Biophysical Investigations of the Cytosolic Iron-Sulfur Cluster Assembly Pathway Late Acting Proteins
… to humans are postulated to deliver a mature [4Fe-4S] cluster to Nar1, an intermediate protein in the pathway. Nar1 is then proposed to deliver the cluster to Met18, Cia2, and Cia1. Met18, Cia2, and Cia1 are referred to as ‘targeting proteins’ in the CIA pathway in eukaryotes. They form a …
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Exploring Prokaryotic Thiamin Biosynthesis: Mechanistic Studies On Thiamin Thiazole Synthase And Pyrimidine Synthase
… We recently were able to show that it was a [4Fe-4S] cluster containing enzyme, and belonged to the radical SAM family. The 4Fe-4S cluster binding motif (CX2-CX4-C) of ThiC is different from the motif (CX3-CX2-C) conventionally used by the other established members of this family. With the …
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Secondary problems caused by the oxyr response to hydrogen peroxide stress in Escherichia coli
… are damaged: DNA, mononuclear iron enzymes, and [4Fe-4S] cluster enzymes. E. coli uses the transcription factor OxyR to sense and respond to H2O2 stress. When the intracellular H2O2 levels rise to 0.2 μM, OxyR is activated via the formation of a disulfide bond, and it induces the transcription of …
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The Biosynthesis and Function of Nitrogenase Metalloclusters
… with the nitrogenase components include the [4Fe-4S] cluster of the Fe protein, and the P-cluster [8Fe7S] and FeMo-cofactor [7Fe-9S-Mo-X-homocitrate], both contained within the MoFe protein. These metal-complexes play a vital role in enzyme activity during electron transport and substrate …
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Studies on two nickel-containing enzymes from Methanosarcina thermophila TM-1
… indicated the presence of two low-potential [4Fe-4S]2+/1+ centers and third high-potential center whose Fe-S configuration is unknown. When reduced with CO, the NilFe-S component exhibited a previously unobserved Ni-Fe-C EPR signal. The Co/Fe-S component contained one [4Fe-4S]2+/1+ cluster, …
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Prebiotic photoreduction and polymerization of cysteinyl peptides.
… peptide sequences that could coordinate a [4Fe-4S]2+ cluster with three cysteinyl ligands, leaving an open coordination position. The stability of the [4Fe-4S] cluster was affected by the intermediates of the citric acid cycle. The iron-sulfur can be reconstituted with the long peptidyl …
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Glutamine Phosphoribosyl Pyrophosphate Amidotransferase From Bacillus Subtilis: Iron-Sulfur Biochemistry and Enzymology
… PRPP amidotransferase was found to be a {4Fe-4S} cluster. In the native enzyme, the cluster exists in the diamagnetic +2 redox state. Treatment of the cluster with oxidants resulted either in no reaction or in oxidative dissolution of the cluster, i.e., a +3 state was not detected. The …
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Biochemical and structural characterization of radical SAM enzymes Elp3 and viperin
… consists of a diverse set of enzymes which use [4Fe-4S] and SAM to initiate radical transformations. These diverse enzymes undergo a common series of steps where SAM is cleaved to yield methionine and a 5’-deoxyadenosyl radical intermediate (5’-dA•), which usually abstracts a hydrogen atom from …
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Studies of thiamine biosynthesis
… conserved cysteine ligands to the essential [4Fe-4S] cluster and has been shown to form a complex with ThiG. With the purpose of studying the mechanistic enzymology by which Thz-P is assembled it was crucial to isolate ThiH in the holo-form. Several expression systems and purification …
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