DEFINITION
Iron-sulfur proteins are proteins characterized by the presence of iron-sulfur clusters containing sulfide-linked di-, tri-, and tetrairon centers in variable oxidation states.
4Fe-4S Clusters
Iron-sulfur proteins
- ferredoxins
- aconitase
- NADH dehydrogenase,
- hydrogenases,
- Coenzyme Q - cytochrome c reductase,
- Succinate - coenzyme Q reductase
- nitrogenase
THE GENES
Iron–sulphur cluster biogenesis and mitochondrial iron homeostasis 2005
The first step of this process occurs in the cytoplasm of prokaryotic organisms or in the mitochondria of eukaryotic organisms. In the higher organisms the clusters are therefore transported out of the mitochondrion to be incorporated into the extramitochondrial enzymes. These organisms also possess a set of proteins involved in the Fe/S clusters transport and incorporation processes that are not homologous to proteins found in procaryotic systems.
CHEMICAL STRUCTURE AND IMAGES
When relevant for the function
- Primary structure
- Secondary structure
- Tertiary structure
- Quaternary structure
Protein Aminoacids Percentage
SYNTHESIS AND TURNOVER
mRNA synthesis
protein synthesis
Iron-Sulfur Cluster assembly
The role of iron regulatory proteins in mammalian iron homeostasis and disease 2006
iron sulfur cluster gsh
THE GENES
post-translational modifications
degradation
The cysteine desulfurase ISCS generates sulfur, which it donates to ISCU. ISCU binds iron, perhaps donated by frataxin, and serves as a scaffold on which nascent iron-sulfur clusters are assembled. ISCA and NFU may also function as scaffold proteins. Ferredoxin (FDX) and glutaredoxin 5 (GRX) provide reducing equivalents, and the chaperones HSCA and HSCB (heat shock cognate proteins A and B, respectively) are likely to enhance scaffold folding and transfer of clusters to recipient apoproteins such as IRP1
CELLULAR FUNCTIONS
cellular localization,
biological function
- Cell signaling and Ligand transport
- Structural proteins
h3. NFU1
Leukoencephalopathy with cysts and hyperglycinemia may result from NFU1 deficiency. 2014
Lipoic acid metabolism defects are new metabolic disorders that cause neurological, cardiomuscular or pulmonary impairment. We report on a patient that presented with progressive neurological regression suggestive of an energetic disease, involving leukoencephalopathy with cysts. Elevated levels of glycine in plasma, urine and CSF associated with intermittent increases of lactate were consistent with a defect in lipoic acid metabolism. Support for the diagnosis was provided by pyruvate dehydrogenase deficiency and multiple mitochondrial respiratory chain deficiency in skin fibroblasts, as well as no lipoylated protein by western blot. Two mutations in the NFU1 gene confirmed the diagnosis. The p.Gly208Cys mutation has previously been reported suggesting a founder effect in Europe.
REGULATION
DIAGNOSTIC US
