Hypusine
Encyclopedia
Hypusine is an unusual amino acid
found in all eukaryote
s and in some archaea
, but not in bacteria
. The only known protein containing hypusine is eukaryotic translation initiation factor
5A (eIF5A
) and a similar protein found in archaebacteria. In humans, two isoforms of eIF-5A have been described: eIF-5A-1 and eIF-5A-2. They are encoded by two different genes. This protein is involved in protein biosynthesis
and promotes the formation of the first peptide bond
. The region surrounding the hypusine residue is highly conserved among the eukaryotes and is essential to the function of eIF-5A. 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. There are two reactions and two enzymes involved:
An excess of hypusine was found in the urine of children and patients with familial hyperlysinemia
.
Hypusine was first isolated from bovine brain by Japanese scientists Shiba et all. in 1971. The name hypusine indicates that the molecule comprises moieties of hydroxyputrescine and lysine.
Amino acid
Amino acids are molecules containing an amine group, a carboxylic acid group and a side-chain that varies between different amino acids. The key elements of an amino acid are carbon, hydrogen, oxygen, and nitrogen...
found in all eukaryote
Eukaryote
A eukaryote is an organism whose cells contain complex structures enclosed within membranes. Eukaryotes may more formally be referred to as the taxon Eukarya or Eukaryota. The defining membrane-bound structure that sets eukaryotic cells apart from prokaryotic cells is the nucleus, or nuclear...
s and in some archaea
Archaea
The Archaea are a group of single-celled microorganisms. A single individual or species from this domain is called an archaeon...
, but not in bacteria
Bacteria
Bacteria are a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria have a wide range of shapes, ranging from spheres to rods and spirals...
. The only known protein containing hypusine is eukaryotic translation initiation factor
Eukaryotic initiation factor
Eukaryotic initiation factors are proteins involved in the initiation phase of eukaryotic translation. They function in forming a complex with the 40S ribosomal subunit and Met-tRNAi called the 43S preinitation complex , recognizing the 5' cap structure of mRNA and recruiting the 43S PIC to mRNA,...
5A (eIF5A
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 - -lysine], which is formed from the polyamine spermidine by two catalytic steps.-Further reading:...
) and a similar protein found in archaebacteria. In humans, two isoforms of eIF-5A have been described: eIF-5A-1 and eIF-5A-2. They are encoded by two different genes. This protein is involved in protein biosynthesis
Protein biosynthesis
Protein biosynthesis is the process in which cells build or manufacture proteins. The term is sometimes used to refer only to protein translation but more often it refers to a multi-step process, beginning with amino acid synthesis and transcription of nuclear DNA into messenger RNA, which is then...
and promotes the formation of the first peptide bond
Peptide bond
This article is about the peptide link found within biological molecules, such as proteins. A similar article for synthetic molecules is being created...
. The region surrounding the hypusine residue is highly conserved among the eukaryotes and is essential to the function of eIF-5A. 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
Lysine
Lysine is an α-amino acid with the chemical formula HO2CCH4NH2. It is an essential amino acid, which means that the human body cannot synthesize it. Its codons are AAA and AAG....
residues. There are two reactions and two enzymes involved:
- 1. Deoxyhypusine synthase catalyzes the cleavage of the polyamine spermidineSpermidineSpermidine is a polyamine involved in cellular metabolism. Its known actions include:#Inhibition of neuronal nitric oxide synthase, nNOS#Assisting the in vitro process of transcribing RNA via stimulation of T4 polynucleotide kinase and T7 RNA polymerase activity; it binds to and precipitates DNA...
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
Hyperlysinemia is an autosomal recessive metabolic disorder characterized by an abnormal increase of lysine in the blood, but appears to be benign. It can be associated with saccharopine dehydrogenase.- Genetics :...
.
Hypusine was first isolated from bovine brain by Japanese scientists Shiba et all. in 1971. The name hypusine indicates that the molecule comprises moieties of hydroxyputrescine and lysine.