Frataxin, a conserved nuclear encoded mitochondrial protein, plays a direct role in iron-sulfur cluster biosynthesis within the ISC assembly pathway. Humans with frataxin deficiency have Friedreich's ataxia, a neurodegenerative disorder characterized by mitochondrial iron overload and disruption in Fe-S cluster synthesis. Biochemical and genetic studies have shown frataxin interacts with the iron-sulfur cluster assembly scaffold protein (in yeast, there are two: Isu1 and Isu2), indicating frataxin plays a direct role in cluster assembly, possibly by serving as an iron chaperone n the assembly pathway. Here we provide molecular details of how yeast frataxin (Yfh1) interacts with Isu1 as a structural module to better understand the multiprotein complex assembly that completes Fe-S cluster assembly; this complex also includes the cysteine desulfurase (Nfs1 in yeast) and the accessory protein (Isd11), together in the mitochondria. Thermodynamic binding parameters for protein partner and iron binding were measured for the yeast orthologs using isothermal titration calorimetry (ITC). Nuclear magnetic resonance spectroscopy was used to provide the molecular details to understand how Yfh1 interacts with Isu1. X-ray absorption studies were used to electronically and structurally characterize how iron is transferred to Isu1 and then incorporated into a Fe-S cluster. These results were combined with previously published data to generate a structural model for how the Fe-S cluster protein assembly complex can come together to accomplish Fe-S cluster assembly. KeywordsIron Chaperone; Frataxin; Yfh1; Isu1; Nfs1; NMR; ITC and Iron-Sulfur Cluster Assembly Iron-sulfur (Fe-S) clusters are central to life and found in nearly every class of organism (1). These ancient but conserved cofactors are bound to proteins involved in a diverse array of essential functions, ranging from DNA repair to respiration. Since Fe-S cofactors are essential for cell viability, it is no surprise proteins that produce these cofactors are tightly controlled and evolutionarily conserved (2-4). In eukaryotes, the major Fe-S cluster assembly machinery is found in the mitochondria. The process of Fe-S cluster synthesis involves the formation of an Fe-S cluster intermediate on a scaffold protein (ISCU in humans or Isu1 or Isu2 in yeast) and subsequent transfer of the cluster to recipient apo-* To whom correspondence should be sent: Department of Biochemistry and Molecular Biology, Wayne State University, School of Medicine, 540 E. Canfield Ave., Detroit, MI 48201. Telephone: 313-577-5712, Fax: 313-577-2765, tstemmle@med.wayne.edu NIH Public Access Author ManuscriptBiochemistry. Author manuscript; available in PMC 2011 October 12. proteins. Formation of the Fe-S cluster by Isu1 requires a source of sulfur and a source of iron. The sulfur originates from cysteine via the activity of the cysteine desulfurase Nfs1, which is coordinated with the essential accessory protein Isd11. The source of the iron for Fe-S clusters has remained a mystery. Frataxin (Y...

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In this work, we have successfully synthesized superparamagnetic nanocomposites, Ce 4– x Sr 1+ x Fe 5– x Zn x O 14+δ (0 ≤ x ≤ 0.45) (CSFZ) (TA1–TA4: x = 0, 0.15, 0.30, and 0.45) via the Nitrate–citrate sol–gel method. X-ray diffraction studies show the formation of single-phase nanocomposites (NCs) and the average crystallite size is found to be 18 nm. Energy-dispersive X-ray spectroscopy analysis supports the formation of the desired product with the expected composition. The scanning electron microscopy image shows that the prepared samples are in spherical shape and highly porous in nature. Most of the particle sizes present in the image are in the range of 5–20 nm. The optical studies show an intense peak at 583 nm corresponding to the instantaneous existence of both Fe 2+ and Fe 3+ intervalence electronic charge transition bands. X-ray photoelectron spectra analysis confirms the presence of elements with their preferred oxidation state. The superparamagnetic nature of the prepared sample was confirmed by vibrating sample magnetometer analysis. Synthesized materials show a low saturate magnetic moment ranging from 0.3400 to 0.1075 emu/g. The coercivity and retentivity value of the synthesized NC is zero. The NCs show high encapsulation efficiency toward ciprofloxacin hydrochloride because of their unique structure and release the loaded drug molecules in a sustained manner up to 10 h at pH 7.4. Such NCs have high potential for use as multifunctional material in various fields such as optical properties, conductivity studies, dielectric, sensor, and drug delivery properties.