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Thioredoxin
Thioredoxin is a class of small redox proteins known to be present in all organisms. It plays a role in many important biological processes, including redox signaling. In humans, thioredoxins are encoded by ''TXN'' and '' TXN2'' genes. Loss-of-function mutation of either of the two human thioredoxin genes is lethal at the four-cell stage of the developing embryo. Although not entirely understood, thioredoxin is linked to medicine through their response to reactive oxygen species (ROS). In plants, thioredoxins regulate a spectrum of critical functions, ranging from photosynthesis to growth, flowering and the development and germination of seeds. Thioredoxins play a role in cell-to-cell communication. Occurrence They are found in nearly all known organisms and are essential for life in mammals. Function The primary function of Thioredoxin (Trx) is the reduction of oxidized cysteine residues and the cleavage of disulfide bonds. Multiple in vitro substrates for thioredoxin have ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Thioredoxin Reductase
Thioredoxin reductases (TR, TrxR) () are enzymes that reduce thioredoxin (Trx). Two classes of thioredoxin reductase have been identified: one class in bacteria and some eukaryotes and one in animals. In bacteria TrxR also catalyzes the reduction of glutaredoxin like proteins known as NrdH. Both classes are flavoproteins which function as homodimers. Each monomer contains a FAD prosthetic group, a NADPH binding domain, and an active site containing a redox-active disulfide bond. Cellular role Thioredoxin reductases are enzymes that catalyze the reduction of thioredoxin and hence they are a central component in the thioredoxin system. Together with thioredoxin (Trx) and NADPH this system's most general description is as a system for reducing disulfide bonds in cells. Electrons are taken from NADPH via TrxR and are transferred to the active site of Trx, which goes on to reduce protein disulfides or other substrates. The Trx system exists in all living cells and has an evolut ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Thioredoxin Fold
The thioredoxin fold is a protein fold common to enzymes that catalyze disulfide bond formation and isomerization. The fold is named for the canonical example thioredoxin and is found in both prokaryotic and eukaryotic proteins. It is an example of an alpha/beta protein fold that has oxidoreductase activity. The fold's spatial topology consists of a four-stranded antiparallel beta sheet sandwiched between three alpha helices. The strand topology is 2134 with 3 antiparallel to the rest. Sequence conservation Despite sequence variability in many regions of the fold, thioredoxin proteins share a common active site sequence with two reactive cysteine residues: Cys-X-Y-Cys, where X and Y are often but not necessarily hydrophobic amino acids. The reduced form of the protein contains two free thiol groups at the cysteine residues, whereas the oxidized form contains a disulfide bond between them. Disulfide bond formation Different thioredoxin fold-containing proteins vary great ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Glutaredoxin
Glutaredoxins (also known as Thioltransferase) are small redox enzymes of approximately one hundred amino-acid residues that use glutathione as a cofactor. In humans this oxidation repair enzyme is also known to participate in many cellular functions, including redox signaling and regulation of glucose metabolism. Glutaredoxins are oxidized by substrates, and reduced non-enzymatically by glutathione. In contrast to thioredoxins, which are reduced by thioredoxin reductase, no oxidoreductase exists that specifically reduces glutaredoxins. Instead, glutaredoxins are reduced by the oxidation of glutathione. Reduced glutathione is then regenerated by glutathione reductase. Together these components compose the glutathione system. Like thioredoxin, which functions in a similar way, glutaredoxin possesses an active centre disulfide bond. It exists in either a reduced or an oxidized form where the two cysteine residues are linked in an intramolecular disulfide bond. Glutaredoxins fun ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
TXN2
Thioredoxin, mitochondrial also known as thioredoxin-2 is a protein that in humans is encoded by the ''TXN2'' gene on chromosome 22. This nuclear gene encodes a mitochondrial member of the thioredoxin family, a group of small multifunctional redox-active proteins. The encoded protein may play important roles in the regulation of the mitochondrial membrane potential and in protection against oxidant-induced apoptosis. Structure As a thioredoxin, TXN2 is a 12-kDa protein characterized by the redox active site Trp-Cys-Gly-Pro-Cys. In its oxidized (inactive) form, the two cysteines form a disulfide bond. This bond is then reduced by thioredoxin reductase and NADPH to a dithiol, which serves as a disulfide reductase. In contrast to TXN1, TXN2 contains a putative N-terminal mitochondrial targeting sequence, responsible for its mitochondria localization, and lacks structural cysteines. Two mRNA transcripts of the ''TXN2'' gene differ by ~330 bp in the length of the 3′-untransl ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
ASK1
Apoptosis signal-regulating kinase 1 (ASK1) also known as mitogen-activated protein kinase 5 (MAP3K5) is a member of MAP kinase family and as such a part of mitogen-activated protein kinase pathway. It activates c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinases in a Raf-independent fashion in response to an array of stresses such as oxidative stress, endoplasmic reticulum stress and calcium influx. ASK1 has been found to be involved in cancer, diabetes, rheumatoid arthritis, cardiovascular and neurodegenerative diseases. ''MAP3K5'' gene coding for the protein is located on chromosome 6 at locus 6q22.33. and the transcribed protein contains 1,374 amino acids with 11 kinase subdomains. Northern blot analysis shows that MAP3K5 transcript is abundant in human heart and pancreas. Mechanism of activation Under nonstress conditions ASK1 is oligomerized (a requirement for its activation) through its C-terminal coiled-coil domain (CCC), but remains in an inacti ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Glutathione
Glutathione (GSH, ) is an antioxidant in plants, animals, fungi, and some bacteria and archaea. Glutathione is capable of preventing damage to important cellular components caused by sources such as reactive oxygen species, free radicals, peroxides, lipid peroxides, and heavy metals. It is a tripeptide with a gamma peptide linkage between the carboxyl group of the glutamate side chain and cysteine. The carboxyl group of the cysteine residue is attached by normal peptide linkage to glycine. Biosynthesis and occurrence Glutathione biosynthesis involves two adenosine triphosphate-dependent steps: *First, γ-glutamylcysteine is synthesized from L-glutamate and cysteine. This conversion requires the enzyme glutamate–cysteine ligase (GCL, glutamate cysteine synthase). This reaction is the rate-limiting step in glutathione synthesis. *Second, glycine is added to the C-terminal of γ-glutamylcysteine. This condensation is catalyzed by glutathione synthetase. While all anim ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Nicotinamide Adenine Dinucleotide Phosphate
Nicotinamide adenine dinucleotide phosphate, abbreviated NADP or, in older notation, TPN (triphosphopyridine nucleotide), is a cofactor used in anabolic reactions, such as the Calvin cycle and lipid and nucleic acid syntheses, which require NADPH as a reducing agent ('hydrogen source'). It is used by all forms of cellular life. NADPH is the reduced form of NADP. NADP differs from NAD by the presence of an additional phosphate group on the 2' position of the ribose ring that carries the adenine moiety. This extra phosphate is added by NAD+ kinase and removed by NADP+ phosphatase. Biosynthesis NADP In general, NADP+ is synthesized before NADPH is. Such a reaction usually starts with NAD+ from either the de-novo or the salvage pathway, with NAD+ kinase adding the extra phosphate group. ADP-ribosyl cyclase allows for synthesis from nicotinamide in the salvage pathway, and NADP+ phosphatase can convert NADPH back to NADH to maintain a balance. Some forms of the NAD+ kina ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Tertiary Structure
Protein tertiary structure is the three dimensional shape of a protein. The tertiary structure will have a single polypeptide chain "backbone" with one or more protein secondary structures, the protein domains. Amino acid side chains may interact and bond in a number of ways. The interactions and bonds of side chains within a particular protein determine its tertiary structure. The protein tertiary structure is defined by its atomic coordinates. These coordinates may refer either to a protein domain or to the entire tertiary structure.Branden C. and Tooze J. "Introduction to Protein Structure" Garland Publishing, New York. 1990 and 1991. A number of tertiary structures may fold into a quaternary structure.Kyte, J. "Structure in Protein Chemistry." Garland Publishing, New York. 1995. History The science of the tertiary structure of proteins has progressed from one of hypothesis to one of detailed definition. Although Emil Fischer had suggested proteins were made of poly ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Sequence Motif
In biology, a sequence motif is a nucleotide or amino-acid sequence pattern that is widespread and usually assumed to be related to biological function of the macromolecule. For example, an ''N''-glycosylation site motif can be defined as ''Asn, followed by anything but Pro, followed by either Ser or Thr, followed by anything but Pro residue''. Overview When a sequence motif appears in the exon of a gene, it may encode the "structural motif" of a protein; that is a stereotypical element of the overall structure of the protein. Nevertheless, motifs need not be associated with a distinctive secondary structure. " Noncoding" sequences are not translated into proteins, and nucleic acids with such motifs need not deviate from the typical shape (e.g. the "B-form" DNA double helix). Outside of gene exons, there exist regulatory sequence motifs and motifs within the " junk", such as satellite DNA. Some of these are believed to affect the shape of nucleic acids (see for exampl ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Redox
Redox (reduction–oxidation, , ) is a type of chemical reaction in which the oxidation states of substrate (chemistry), substrate change. Oxidation is the loss of Electron, electrons or an increase in the oxidation state, while reduction is the gain of electrons or a decrease in the oxidation state. There are two classes of redox reactions: * ''Electron-transfer'' – Only one (usually) electron flows from the reducing agent to the oxidant. This type of redox reaction is often discussed in terms of redox couples and electrode potentials. * ''Atom transfer'' – An atom transfers from one substrate to another. For example, in the rusting of iron, the oxidation state of iron atoms increases as the iron converts to an oxide, and simultaneously the oxidation state of oxygen decreases as it accepts electrons released by the iron. Although oxidation reactions are commonly associated with the formation of oxides, other chemical species can serve the same function. In hydrogen ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Oxidative Stress
Oxidative stress reflects an imbalance between the systemic manifestation of reactive oxygen species and a biological system's ability to readily detoxify the reactive intermediates or to repair the resulting damage. Disturbances in the normal redox state of cells can cause toxic effects through the production of peroxides and free radicals that damage all components of the cell, including proteins, lipids, and DNA. Oxidative stress from oxidative metabolism causes base damage, as well as strand breaks in DNA. Base damage is mostly indirect and caused by the reactive oxygen species generated, e.g., O2− ( superoxide radical), OH ( hydroxyl radical) and H2O2 ( hydrogen peroxide). Further, some reactive oxidative species act as cellular messengers in redox signaling. Thus, oxidative stress can cause disruptions in normal mechanisms of cellular signaling. In humans, oxidative stress is thought to be involved in the development of attention deficit hyperactivity disorder, cancer ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
