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Human frataxin is an allosteric switch that activates the Fe-S cluster biosynthetic complex.
In vitro evidence is provided that human frataxin binds to a Nfs1, Isd11, and Isu2 complex to generate the four-component core machinery for Fe-S cluster biosynthesis, and a model in which cellular fr ataxin levels regulate human Fe- S cluster biosynthetic activities is proposed that has implications for mitochondrial dysfunction, oxidative stress response, and both neurodegenerative and cardiovascular disease. Expand
Mechanism and energetics of green fluorescent protein chromophore synthesis revealed by trapped intermediate structures
The protein architecture contains a dramatic ≈80° bend in the central helix, which focuses distortions at G67 to promote ring formation from amino acids S65, Y66, and G67, and this leads directly to a conjugation-trapping mechanism, in which a thermodynamically unfavorable cyclization reaction is coupled to an electronic conjugations trapping step, to drive chromophore maturation. Expand
Nickel superoxide dismutase structure and mechanism.
The 1.30 A resolution crystal structure of nickel superoxide dismutase (NiSOD) identifies a novel SOD fold, assembly, and Ni active site that provides almost all interactions critical for metal binding and catalysis, and thus will likely be diagnostic of NiSODs. Expand
Structure of human Fe–S assembly subcomplex reveals unexpected cysteine desulfurase architecture and acyl-ACP–ISD11 interactions
The unexpected architecture for the SDA complex provides a framework for understanding interactions with acceptor proteins for sulfur-containing biosynthetic pathways, elucidating mechanistic details of eukaryotic Fe–sulfur cluster biosynthesis, and clarifying how defects in Fe–S cluster assembly lead to diseases such as Friedreich’s ataxia. Expand
Human Frataxin Activates Fe–S Cluster Biosynthesis by Facilitating Sulfur Transfer Chemistry
Radiolabeling experiments indicate FXN accelerates the accumulation of sulfur on ISCU2 and that the resulting persulfide species is viable in the subsequent synthesis of Fe–S clusters, which cannot be fully explained by the hypothesis that FXN functions as an iron donor for Fe-S cluster biosynthesis. Expand
Superoxide dismutase from the eukaryotic thermophile Alvinella pompejana: structures, stability, mechanism, and insights into amyotrophic lateral sclerosis.
Identification, cloning, characterization, X-ray scattering, and crystal structure determinations show that A. pompejana SOD (ApSOD) is superstable, homologous, and informative, and suggest that the eukaryote provides macromolecules highly similar to those from humans, but with enhanced stability more suitable for scientific and medical applications. Expand
Effector role reversal during evolution: the case of frataxin in Fe-S cluster biosynthesis.
Surprisingly, the results reveal that activation or inhibition by the frataxin homologue is determined by which cysteine desulfurase is present and not by the identity of theFrataxIn homologue, which appears to be an unusual example in which modifications to an enzyme during evolution inverts the mode of control imparted by a regulatory molecule. Expand
Enzymes for the homeland defense: optimizing phosphotriesterase for the hydrolysis of organophosphate nerve agents.
The discovery of additional PTE variants with significant improvements in catalytic activities relative to that of the wild-type enzyme support a combinatorial strategy of rational design and directed evolution as a powerful tool for the discovery of more efficient enzymes for the detoxification of organophosphate nerve agents. Expand
Frataxin Accelerates [2Fe-2S] Cluster Formation on the Human Fe-S Assembly Complex.
It is found that common surrogate electron donor molecules intercepted Fe-S cluster intermediates and formed high-molecular weight species (HMWS), which are associated with iron, sulfide, and thiol-containing proteins and have properties of a heterogeneous solubilized mineral with spectroscopic properties remarkably reminiscent of those of [4Fe-4S] clusters. Expand
Carbon monoxide dehydrogenase from Clostridium thermoaceticum was methylated such that all bound methyl groups could subsequently react with CO and coenzyme A (or OH-) to yield acetyl-coenzyme AExpand