• Using the Iron Sulfur cluster biogenesis in S. cerevisiae as a test case we indicate how this procedure can be used to analyze and validate the network model against experimental results. (biomedcentral.com)
  • Iron-Sulfur Cluster biogenesis) or complex pathways with an unclear reaction and regulation network, (e. g. cell cycle). (biomedcentral.com)
  • It is an iron-sulfur transferase that contains binding sites for [2Fe-2S] and [4Fe-4S] clusters. (wikipedia.org)
  • ISCU encodes a component of the iron-sulfur (Fe-S) cluster scaffold responsible for the synthesis and maturation of [2Fe-2S] and [4Fe-4S] clusters. (wikipedia.org)
  • Fe-S clusters are cofactors that play a role in the function of a diverse set of enzymes, including those that regulate metabolism, iron homeostasis, and oxidative stress response. (wikipedia.org)
  • Along with its most important role as central reductant, T[SH] 2 have also been assumed to regulate the activation of iron-sulfur cluster proteins (Fe/S). Fe/S clusters are versatile cofactors of various proteins and execute a much broader range of essential biological processes viz. (frontiersin.org)
  • One such class of pathways is involved in the biogenesis of Iron-Sulfur Clusters (ISC). (biomedcentral.com)
  • Hence, we suggest that, by designing highly potent and specific inhibitors of TryR enzyme, inhibition of T[SH] 2 reduction and overall inhibition of most of the downstream pathways including Fe/S protein activation reactions, can be accomplished. (frontiersin.org)
  • Increasing amounts of data that can be mined for information about how proteins in cells assemble as metabolic pathways, signal transduction pathways, and gene circuits, are generated each day. (biomedcentral.com)
  • Iron-sulfur cluster assembly enzyme ISCU, mitochondrial is a protein that in humans is encoded by the ISCU gene. (wikipedia.org)
  • A deficiency of ISCU is associated with a mitochondrial myopathy with lifelong exercise intolerance where only minor exertion causes tachycardia, shortness of breath, muscle weakness and myalgia. (wikipedia.org)
  • ISCU mutations have been found in patients with hereditary mitochondrial myopathy with exercise intolerance and lactic acidosis. (wikipedia.org)
  • This disease is a result of a deficiency of ISCU that corresponds to the deficiency of mitochondrial iron-sulfur proteins and impaired muscle oxidative metabolism. (wikipedia.org)
  • As a test case, we reconstruct the topology of the reaction and regulatory network for the mitochondrial ISC biogenesis pathway in S. cerevisiae . (biomedcentral.com)
  • A putative role for frataxin in directly regulating mitochondrial iron import is discarded from our analysis, which agrees with also published experimental results. (biomedcentral.com)
  • The more than likely absence of known mechanistic and kinetic data for each of the individual proteins in a novel pathway hinders the process of translating network topology into a mathematical model. (biomedcentral.com)
  • In pursuit of this aim, a systems biology approach was undertaken to get an insight into the overall picture to unravel how T[SH] 2 synthesis and reduction is linked with the regulation of Fe/S cluster proteins and controls the redox homeostasis at a larger scale. (frontiersin.org)
  • Although, several Fe/S cluster proteins and their roles have been identified in Leishmania, some of the components of how T[SH] 2 is involved in the regulation of Fe/S proteins remains to be explored. (frontiersin.org)
  • It encodes an iron-sulfur (Fe-S) cluster scaffold protein involved in [2Fe-2S] and [4Fe-4S] cluster synthesis and maturation. (wikipedia.org)
  • In one process, the [2Fe-2S] cluster transiently assembles on ISCU and is then transferred to GLRX5 in a cysteine desulfurase complex NFS1-LYRM4/ISD11 dependent process. (wikipedia.org)
  • ISCU has been shown to have 235 binary protein-protein interactions including 79 co-complex interactions. (wikipedia.org)
  • Halide, 2OG, and (lastly) O2 all coordinate directly to the cofactor to initiate its conversion to a cis-halo-oxo-iron(IV) (haloferryl) complex, which abstracts hydrogen (Hâ ¢) from the non-coordinating prime substrate to enable radicaloid carbon-halogen coupling. (bvsalud.org)
  • For example, the involvement of proteins X, Y and Z in a process does not elucidate if X catalyzes a reaction that produces a substrate for another reaction catalyzed by Z or by Y, or if X modulates Y or Z activity. (biomedcentral.com)
  • To achieve such a goal, strategies that combine the different theoretical and computational methods to identify proteins and generate a set of plausible alternative network topologies for the process of interest are needed. (biomedcentral.com)
  • The mechanistic data imply (i) that BesD may have evolved from a hydroxylase ancestor either relatively recently or under weak selective pressure for efficient chlorination and (ii) that acquisition of its activity may have involved the emergence of linkage between l-Lys binding and chloride coordination following the loss of the anionic protein-carboxylate iron ligand present in extant hydroxylases. (bvsalud.org)
  • The natural lanthanide-binding protein lanmodulin (LanM)4,5 is a sustainable alternative to conventional solvent-extraction-based separation6. (bvsalud.org)
  • Predictions regarding how proteins act in ISC biogenesis are validated by comparison with published experimental results. (biomedcentral.com)