title: Posttranslational synthesis of hypusine: evolutionary progression and specificity of the hypusine modification.
abstract: A naturally occurring unusual amino acid, hypusine [N (epsilon)-(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.
authors.affiliation: Oral and Pharyngeal Cancer Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD 20892-4340, USA.
authors.forename: E C
authors.initials: EC
authors.lastname: Wolff
authors.forename: K R
authors.initials: KR
authors.lastname: Kang
authors.forename: Y S
authors.initials: YS
authors.lastname: Kim
authors.forename: M H
authors.initials: MH
authors.lastname: Park
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D005075:Biological Evolution; D006801:Humans; D008239:Lysine / Q000031:analogs & derivatives* / Q000096:biosynthesis; D006899:Mixed Function Oxygenases / Q000378:metabolism; D000587:Oxidoreductases Acting on CH-NH Group Donors / Q000037:antagonists & inhibitors / Q000378:metabolism; D010445:Peptide Elongation Factors / Q000502:physiology; D010448:Peptide Initiation Factors / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D011499:Protein Processing, Post-Translational / Q000235:genetics; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D016415:Sequence Alignment; D013095:Spermidine / Q000378:metabolism; D013379:Substrate Specificity; D000097574:Eukaryotic Translation Initiation Factor 5A
chemical_list: D008239:Lysine; D006899:Mixed Function Oxygenases; D000587:Oxidoreductases Acting on CH-NH Group Donors; D010445:Peptide Elongation Factors; D010448:Peptide Initiation Factors; D016601:RNA-Binding Proteins; D013095:Spermidine; D000097574:Eukaryotic Translation Initiation Factor 5A; C115531:aIF-5A; C020746:factor EF-P; C100028:hypusine; C047991:deoxyhypusine hydroxylase; C063507:deoxyhypusine synthase