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Amino Acids

, Volume 33, Issue 2, pp 341–350 | Cite as

Posttranslational synthesis of hypusine: evolutionary progression and specificity of the hypusine modification

  • E. C. Wolff
  • K. R. Kang
  • Y. S. Kim
  • M. H. Park
Review Article
First Online:

Summary.

A naturally occurring unusual amino acid, hypusine [N ɛ-(4-amino-2-hydroxybutyl)-lysine] is a component of a single cellular protein, eukaryotic translation initiation factor 5A (eIF5A). It is a modified lysine with structural contribution from the polyamine spermidine. Hypusine is formed in a novel posttranslational modification that involves two enzymes, deoxyhypusine synthase (DHS) and deoxyhypusine hydroxylase (DOHH). eIF5A and deoxyhypusine/hypusine modification are essential for growth of eukaryotic cells. The hypusine synthetic pathway has evolved in eukaryotes and eIF5A, DHS and DOHH are highly conserved, suggesting maintenance of a fundamental cellular function of eIF5A through evolution. The unique feature of the hypusine modification is the strict specificity of the enzymes toward its substrate protein, eIF5A. Moreover, DHS exhibits a narrow specificity toward spermidine. In view of the extraordinary specificity and the requirement for hypusine-containing eIF5A for mammalian cell proliferation, eIF5A and the hypusine biosynthetic enzymes present new potential targets for intervention in aberrant cell proliferation.

Keywords: Hypusine – eIF5A – Posttranslational modification – Deoxyhypusine synthase – Deoxyhypusine hydroxylase – Polyamine 

Abbreviations:

aIF5A

archaeal initiation factor 5A

DHS

deoxyhypusine synthase

DOHH

deoxyhypusine hydroxylase

EF-P

elongation factor P

eIF5A

eukaryotic translation initiation factor 5A

eIF5A-1

primary isoform of eIF5A

eIF5A-2

secondary isoform of eIF5A

eIF5A(Dhp)

eIF5A intermediate containing deoxyhypusine

eIF5A(Hpu)

eIF5A active form containing hypusine

eIF5A(Lys)

eIF5A precursor

GC7

N 1-guanyl-1,7-diaminoheptane

HEAT-repeat

alpha-helical structural motif characteristic of Huntingtin, elongation factor 3E, a subunit of protein phosphatase 2A, and the target of rapamycin

NAD

nicotinamide adenine dinucleotide

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Copyright information

© Springer-Verlag 2007

Authors and Affiliations

  • E. C. Wolff
    • 1
  • K. R. Kang
    • 1
    • 2
  • Y. S. Kim
    • 1
  • M. H. Park
    • 1
  1. 1.Oral and Pharyngeal Cancer Branch, National Institute of Dental and Craniofacial ResearchNational Institutes of HealthBethesdaU.S.A.
  2. 2.Department of Biochemistry, College of Medicine and Institute of Health ScienceGyeongsang National UniversityJinjuSouth Korea

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