Hypusine is an uncommon
amino acid
Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although hundreds of amino acids exist in nature, by far the most important are the alpha-amino acids, which comprise proteins. Only 22 alpha a ...
found in all
eukaryotes and in some
archaea, but not in
bacteria
Bacteria (; singular: bacterium) are ubiquitous, mostly free-living organisms often consisting of one Cell (biology), biological cell. They constitute a large domain (biology), domain of prokaryotic microorganisms. Typically a few micrometr ...
. 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
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 e ...
and
EIF5A2
Eukaryotic translation initiation factor 5A-2 is a protein that in humans is encoded by the ''EIF5A2'' gene
In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." me ...
. 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
Post-translational modification (PTM) is the covalent and generally enzymatic modification of proteins following protein biosynthesis. This process occurs in the endoplasmic reticulum and the golgi apparatus. Proteins are synthesized by ribos ...
of one of the
lysyl
Lysine (symbol Lys or K) is an α-amino acid that is a biosynthesis, precursor to many proteins. It contains an α-amino group (which is in the protonation, protonated form under biological conditions), an α-carboxylic acid group (which is in ...
residues. Two reactions and two enzymes are involved:
*1.
Deoxyhypusine synthase catalyzes the cleavage of the polyamine
spermidine
Spermidine is a polyamine compound () found in ribosomes and living tissues and having various metabolic functions within organisms. It was originally isolated from semen.
Function
Spermidine is an aliphatic polyamine. Spermidine synthase (SP ...
and transfer of its 4-aminobutyl moiety to the ε-amino group of one specific lysine residue of the eIF-5A precursor to form deoxyhypusine and
1,3-diaminopropane.
*2.
Deoxyhypusine hydroxylase mediates the formation of hypusine by addition of a hydroxyl group to the deoxyhypusine residue.
An excess of hypusine was found in the urine of children and patients with familial
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.
Hyper ...
.
Hypusine was first isolated from bovine brain by Japanese scientists Shiba ''et al.'' in 1971.
The name ''hypusine'' indicates that the molecule comprises moieties of hydroxyputrescine and lysine.
See also
*
''n''-Butylamine, related to 4-aminobutyl group of deoxyhypusine
*
Putrescine
Putrescine is an organic compound with the formula (CH2)4(NH2)2. It is a colorless solid that melts near room temperature. It is classified as a diamine. Together with cadaverine, it is largely responsible for the foul odor of putrefying flesh, ...
*
Diphthamide
Diphthamide is a post-translationally modified histidine amino acid found in archaeal and eukaryotic elongation factor 2 (eEF-2).
Structure
Diphthamide is proposed to be a 2- -carboxyamido-3-(trimethylammonio)propylistidine. Though this structure ...
, another translation-related uncommon amino acid
**
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. Thi ...
, eukaryotic elongation factor 2, utilizing diphthamide
References
Amino acids
Non-proteinogenic amino acids
{{Non-proteinogenic amino acids