Hypusine

Hypusine
Names
IUPAC name
N6-[(2R)-4-amino-2-hydroxybutyl]-L-lysine
Systematic IUPAC name
(2S)-2-Amino-6-{[(2R)-4-amino-2-hydroxybutyl]amino}hexanoic acid
Other names
N6-(4-Amino-2-hydroxybutyl)lysine
Identifiers
3D model (JSmol)
ChEBI
ChemSpider
MeSH Hypusine
UNII
  • InChI=1S/C10H23N3O3/c11-5-4-8(14)7-13-6-2-1-3-9(12)10(15)16/h8-9,13-14H,1-7,11-12H2,(H,15,16)/t8-,9+/m1/s1 N
    Key: BZUIJMCJNWUGKQ-BDAKNGLRSA-N N
  • C(CCNC[C@@H](CCN)O)C[C@@H](C(=O)O)N
Properties
C10H23N3O3
Molar mass 233.312 g·mol−1
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
N verify (what is YN ?)
Infobox references

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 the archaeal homolog aIF5A.[1] 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.[2] 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 (DHPS, DHS) catalyzes the cleavage of the polyamine spermidine 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. This step is universal among eukaryotes and archaea.[3]
  2. Deoxyhypusine hydroxylase mediates the formation of hypusine by addition of a hydroxyl group to the deoxyhypusine residue. This step is universal among eukaryotes, but absent in some archaea (the Euryarchaea).[3]

Inhibition of DHPS causes cell cycle arrest in all tested archaea (Sulfolobus, Halobacterium halobium, Haloferax mediterranei).[3]

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 al. in 1971.[4] The name hypusine indicates that the molecule comprises moieties of hydroxyputrescine and lysine.

See also

References

  1. ^ Park MH (2006). "The post-translational synthesis of a polyamine-derived amino acid, hypusine, in the eukaryotic translation initiation factor 5A (eIF5A)". Journal of Biochemistry. 139 (2): 161–169. doi:10.1093/jb/mvj034. PMC 2494880. PMID 16452303.
  2. ^ Cano VS, Jeon GA, Johansson HE, Henderson CA, Park JH, Valentini SR, Hershey JW, Park MH (2008). "Mutational analyses of human eIF5A-1 -- Identification of amino acid residues critical for eIF5A activity and hypusine modification". FEBS Journal. 275 (1): 44–58. doi:10.1111/j.1742-4658.2007.06172.x. PMC 2536608. PMID 18067580.
  3. ^ a b c Jansson, B. P. Mattias; Malandrin, Laurence; Johansson, Hans E. (15 February 2000). "Cell Cycle Arrest in Archaea by the Hypusination Inhibitor N 1 -Guanyl-1,7-Diaminoheptane". Journal of Bacteriology. 182 (4): 1158–1161. doi:10.1128/jb.182.4.1158-1161.2000.
  4. ^ Shiba T, Mizote H, Kaneko T, Nakajima T, Kakimoto Y, Isamu S (1971). "Hypusine, a new amino acid occurring in bovine brain. Isolation and structural determination". Biochimica et Biophysica Acta. 244 (3): 523–531. doi:10.1016/0304-4165(71)90069-9. PMID 4334286.
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