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Hypusine
Hypusine is an uncommon amino acid found in all eukaryotes and in some archaea, but not in bacteria. The only known proteins containing the hypusine residue is eukaryotic translation initiation factor 5A (eIF-5A) and a similar protein found in archaea. In humans, two isoforms of eIF-5A have been described: eIF5A-1 and eIF5A-2. They are encoded by two distinct genes EIF5A and EIF5A2. The protein is involved in protein biosynthesis and promotes the formation of the first peptide bond. The region surrounding the hypusine residue is highly conserved and is essential to the function of eIF5A. Thus, hypusine and eIF-5A appear to be vital for the viability and proliferation of eukaryotic cells. Hypusine is formed in eIF-5A by post-translational modification of one of the lysyl residues. Two reactions and two enzymes are involved: *1. Deoxyhypusine synthase catalyzes the cleavage of the polyamine spermidine and transfer of its 4-aminobutyl moiety to the ε-amino group of one spec ...
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DHPS
Deoxyhypusine synthase is an enzyme that in humans is encoded by the ''DHPS'' gene. The unusual amino acid hypusine is formed posttranslationally and is only found in a single cellular protein, eukaryotic translation initiation factor 5A ( EIF5A, EIF5A2). In the first step of hypusine biosynthesis, deoxyhypusine synthase catalyzes the NAD-dependent transfer of the butylamine moiety of spermidine to the epsilon-amino group of a specific lysine residue of the EIF5A precursor protein to form the intermediate deoxyhypusine residue. This gene consists of nine exons An exon is any part of a gene that will form a part of the final mature RNA produced by that gene after introns have been removed by RNA splicing. The term ''exon'' refers to both the DNA sequence within a gene and to the corresponding sequence i ... spanning 6.6 kb. Three transcript variants have been isolated. However, only transcript variant 1 encodes an active protein. The shorter variants may act as modulating fac ...
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EIF5A
Eukaryotic translation initiation factor 5A-1 is a protein that in humans is encoded by the ''EIF5A'' gene. It is the only known protein to contain the unusual amino acid hypusine 'N''ε-(4-amino-2-hydroxybutyl)-lysine which is synthesized on eIF5A at a specific lysine residue from the polyamine spermidine by two catalytic steps. EF-P is the bacterial homolog of eIF5A, which is modified post-translationally in a similar but distinct way. Both proteins are believed to catalyze peptide bond formation and help resolve ribosomal stalls, making them elongation factors despite the "initiation factor" name originally assigned. Faundes-Banka syndrome Germline deleterious heterozygous ''EIF5A'' variants cause Faundes-Banka syndrome. This rare human disorder is characterized by variable combinations of developmental delay, microcephaly Microcephaly (from Neo-Latin ''microcephalia'', from Ancient Greek μικρός ''mikrós'' "small" and κεφαλή ''kephalé'' "head") is a me ...
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Deoxyhypusine Monooxygenase
In enzymology, a deoxyhypusine monooxygenase () is an enzyme that catalyzes the chemical reaction :protein ''N''6-(4-aminobutyl)-L-lysine + AH2 + O2 \rightleftharpoons protein ''N''6- ''R'')-4-amino-2-hydroxybutylL-lysine + A + H2O The 3 substrates of this enzyme are a protein-bound ''N''6-(4-aminobutyl)-L-lysine, an electron acceptor AH2, and O2, and its 3 products are protein-bound ''N''6- ''R'')-4-amino-2-hydroxybutylL-lysine, the reduction product A, and H2O. This enzyme belongs to the family of oxidoreductases, specifically those acting on paired donors, with O2 as oxidant and incorporation or reduction of oxygen. The oxygen incorporated need not be derive from O miscellaneous. The systematic name of this enzyme class is deoxyhypusine,hydrogen-donor:oxygen oxidoreductase (2-hydroxylating). Other names in common use include deoxyhypusine hydroxylase, and deoxyhypusine dioxygenase. Mammalian proteins The HUGO symbol for human gene and protein is DOHH, the full name is de ...
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Amino Acid
Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although over 500 amino acids exist in nature, by far the most important are the 22 α-amino acids incorporated into proteins. Only these 22 appear in the genetic code of life. Amino acids can be classified according to the locations of the core structural functional groups ( alpha- , beta- , gamma- amino acids, etc.); other categories relate to polarity, ionization, and side-chain group type ( aliphatic, acyclic, aromatic, polar, etc.). In the form of proteins, amino-acid '' residues'' form the second-largest component (water being the largest) of human muscles and other tissues. Beyond their role as residues in proteins, amino acids participate in a number of processes such as neurotransmitter transport and biosynthesis. It is thought that they played a key role in enabling life on Earth and its emergence. Amino acids are formally named by the IUPAC- IUBMB Joint Commi ...
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Post-translational Modification
In molecular biology, post-translational modification (PTM) is the covalent process of changing proteins following protein biosynthesis. PTMs may involve enzymes or occur spontaneously. Proteins are created by ribosomes, which translation (biology), translate mRNA into polypeptide chains, which may then change to form the mature protein product. PTMs are important components in cell signal transduction, signalling, as for example when prohormones are converted to hormones. Post-translational modifications can occur on the amino acid side chains or at the protein's C-terminus, C- or N-terminus, N- termini. They can expand the chemical set of the 22 proteinogenic amino acid, amino acids by changing an existing functional group or adding a new one such as phosphate. Phosphorylation is highly effective for controlling the enzyme activity and is the most common change after translation. Many eukaryotic and prokaryotic proteins also have carbohydrate molecules attached to them in a pro ...
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Alpha-Amino Acids
Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although over 500 amino acids exist in nature, by far the most important are the 22 α-amino acids incorporated into proteins. Only these 22 appear in the genetic code of life. Amino acids can be classified according to the locations of the core structural functional groups ( alpha- , beta- , gamma- amino acids, etc.); other categories relate to polarity, ionization, and side-chain group type ( aliphatic, acyclic, aromatic, polar, etc.). In the form of proteins, amino-acid '' residues'' form the second-largest component (water being the largest) of human muscles and other tissues. Beyond their role as residues in proteins, amino acids participate in a number of processes such as neurotransmitter transport and biosynthesis. It is thought that they played a key role in enabling life on Earth and its emergence. Amino acids are formally named by the IUPAC- IUBMB Joint Commiss ...
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Eukaryotic Initiation Factor
Eukaryotic initiation factors (eIFs) are proteins or protein complexes involved in the initiation phase of eukaryotic translation. These proteins help stabilize the formation of ribosomal preinitiation complexes around the start codon and are an important input for post-transcription gene regulation. Several initiation factors form a complex with the small 40S ribosomal subunit and Met- tRNAiMet called the 43S preinitiation complex (43S PIC). Additional factors of the eIF4F complex (eIF4A, E, and G) recruit the 43S PIC to the five-prime cap structure of the mRNA, from which the 43S particle scans 5'-->3' along the mRNA to reach an AUG start codon. Recognition of the start codon by the Met-tRNAiMet promotes gated phosphate and eIF1 release to form the 48S preinitiation complex (48S PIC), followed by large 60S ribosomal subunit recruitment to form the 80S ribosome. There exist many more eukaryotic initiation factors than prokaryotic initiation factors, reflecting the gre ...
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EIF5A2
Eukaryotic translation initiation factor 5A-2 is a protein that in humans is encoded by the ''EIF5A2'' gene In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei .... References Further reading

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Hyperlysinemia
Hyperlysinemia is an autosomal recessive metabolic disorder characterized by an abnormal increase of lysine in the blood, but appears to be benign. It is caused by mutations in '' AASS'', which encodes α-aminoadipic semialdehyde synthase. Hyperlysinemia is associated with ectopia lentis (a displacement or malposition of the eye's crystalline lens) in humans. Signs and symptoms While hyperlysinemia typically causes no health problems, patients may exhibit behavioral abnormalities, delayed speech and language development, infantile hypotonia, intellectual disability, microcephaly, neurodevelopmental delay, psychomotor retardation, seizures, short attention spans, and short stature. Genetics Hyperlysinemia is inherited in an autosomal recessive manner. This means the defective gene responsible for the disorder is located on an autosome An autosome is any chromosome that is not a sex chromosome. The members of an autosome pair in a diploid cell have the same morphology ...
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EEF2
Eukaryotic elongation factor 2 is a protein that in humans is encoded by the ''EEF2'' gene. It is the archaeal and eukaryotic counterpart of bacterial EF-G. This gene encodes a member of the GTP-binding translation elongation factor family. This protein is an essential factor for protein synthesis. It promotes the GTP-dependent translocation of the ribosome. This protein is completely inactivated by EF-2 kinase phosphorylation. aEF2/eEF2 found in most archaea and eukaryotes, including humans, contains a post translationally modified histidine diphthamide. It is the target of diphtheria toxin (from ''Corynebacterium diphtheriae''), and exotoxin A (from ''Pseudomonas aeruginosa ''Pseudomonas aeruginosa'' is a common Bacterial capsule, encapsulated, Gram-negative bacteria, Gram-negative, Aerobic organism, aerobic–facultative anaerobe, facultatively anaerobic, Bacillus (shape), rod-shaped bacteria, bacterium that can c ...''). The inactivation of EF-2 by toxins inhibits pr ...
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Diphthamide
Diphthamide is a post-translationally modified histidine amino acid found in archaeal and eukaryotic elongation factor 2 (eEF-2). Dipthamide is named after the toxin produced by the bacterium ''Corynebacterium diphtheriae'', which targets diphthamide. Besides this toxin, it is also targeted by exotoxin A from ''Pseudomonas aeruginosa''. It is the only target of these toxins. Structure and biosynthesis Diphthamide is proposed to be a 2- -carboxyamido-3-(trimethylammonio)propylistidine. Though this structure has been confirmed by X-ray crystallography, its stereochemistry is uncertain. Diphthamide is biosynthesized from histidine and ''S''-adenosyl methionine (SAM). The side chain bound to imidazole group and all methyl groups come from SAM. The whole synthesis takes place in three steps: * transfer of 3-amino-3-carboxypropyl group from SAM * transfer of three methyl groups from SAM – synthesis of diphtine * amidation – synthesis of diphthamide In eukaryotes, this biosyn ...
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Polyamine
A polyamine is an organic compound having two or more amino groups. Alkyl polyamines occur naturally, but some are synthetic. Alkylpolyamines are colorless, hygroscopic, and water soluble. Near neutral pH, they exist as the ammonium derivatives. Most aromatic polyamines are crystalline solids at room temperature. Natural polyamines Low-molecular-weight linear polyamines are found in all forms of life. The principal examples are the triamine spermidine and the tetraamine spermine. They are structurally and biosynthetically related to the diamines putrescine and cadaverine. Polyamine metabolism is regulated by the activity of the enzyme ornithine decarboxylase (ODC). Polyamines are found in high concentrations in the mammalian brain. File:Spermidine-2D-skeletal.svg, spermidine File:Spermine.svg, spermine Synthetic polyamines Ethyleneamines are a commercially-important class of synthetic polyamines with ethylene ( linkages); global production capacity was estimated at 385,00 ...
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