Hypusine, a new amino acid occurring in bovine brain

Shiba, Tetsuo; Mizote, Hiroyuki; Kaneko, Takeo; Nakajima, Teruo; Kawaguchi, Yasuo; Sano, Isamu

doi:10.1016/0304-4165(71)90069-9

Cited by 108 publications

(84 citation statements)

References 16 publications

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“…The oxidative cleavage of the hypusyl residue allows its specific distinction from the deoxyhypusyl residue [18]. Harsh oxidation conditions using permanganate and periodate leads to the formation of the lysine form of eIF-5A, formic acid and fl-alanine.…”

Section: Resultsmentioning

confidence: 99%

“…This product can be oxidized to yield the free lysine form ofeIF-5A (precursor), formaldehyde and fl-aminopropionaldehyde [18]. Following oxidative cleavage, the generated radioactively labeled aldehydes can be specifically converted with dimedone, and extracted into the organic phase in analogy to the methods previously described for hydroxyprolyl and hydroxylysyl residues [20].…”

Section: Deoxyhypusine Hydroxylase Assaymentioning

confidence: 99%

“…Another method for discriminating between the two modification states is based on the specific oxidation of the hypusyl residue [18]. In the work presented here, a novel and rapid in vitro assay for monitoring the deoxyhypusine hydroxylase activity is described.…”

Section: Introductionmentioning

confidence: 99%

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Evaluation of the metal ion requirement of the human deoxyhypusine hydroxylase from HeLa cells using a novel enzyme assay

Csonga¹,

Ettmayer²,

Auer³

et al. 1996

FEBS Letters

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Hypusine synthesis in the eukaryotic initiation factor 5A is a unique two-step posttranslational modification. After deoxyhypusine is generated by the deoxyhypusine synthase, the deoxyhypusine hydroxylase (EC 1.14.99.29) catalyzes the formation of mature hypusine. A rapid assay for monitoring the deoxyhypusine hydroxylase activity was established, employing the oxidative cleavage of the hypusyl residue and subsequent extraction of the generated aldehydes. As metal ion chelators have been reported to inhibit the deoxyhypusine hydroxylase, the mechanism of this inhibition and the effect of transition metal ions on the enzyme activity were investigated. A ferric ion appears to be essential for enzymatic activity, the inhibition of which is entirely attributed to the metal ion binding capacity of the chelators.

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Section: Resultsmentioning

confidence: 99%

Section: Deoxyhypusine Hydroxylase Assaymentioning

confidence: 99%

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Evaluation of the metal ion requirement of the human deoxyhypusine hydroxylase from HeLa cells using a novel enzyme assay

Csonga¹,

Ettmayer²,

Auer³

et al. 1996

FEBS Letters

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“…Hypusine [N ε -(4-amino-2-hydroxybutyl)-lysine, or (2S, 9R)-2-11-diamino-9-hydroxy-7-azaundecanoic acid] was discovered from bovine brain extracts in 1971 by Shiba (Shiba et al, 1971) in their search for unusually basic, natural amino acids. Later hypusine was found in various animal tissues as a protein component as well as a free amino acid.…”

Section: Introductionmentioning

confidence: 99%

“…Later hypusine was found in various animal tissues as a protein component as well as a free amino acid. After determination of its chemical structure, this amino acid was named hypusine, based on its two structural components, hydroxyputrescine and lysine (Shiba et al, 1971). However, the origin of the 4-amino-2-hydroxybutyl moiety, the mechanism of its synthesis and the source of hypusine were unknown.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2007

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SummaryA naturally occurring unusual amino acid, hypusine [N ε -(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.

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Dramatic attenuation of hypusine formation on eukaryotic initiation factor 5A during senescence of IMR-90 human diploid fibroblasts

Chen

1997

J. Cell. Physiol.

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Deoxyhypusine synthase catalyzes the conversion of lysine to deoxyhypusine residue on the eukaryotic initiation factor 5A (elF-5A) precursor using spermidine as the substrate. Subsequent hydroxylation of the deoxyhypusine residue completes hypusine formation on elF-5A. Hypusine formation is one of the most specific polyamine-dependent biochemical events in eukaryotic cells. Although changes in polyamine metabolism have been demonstrated in human diploid fibroblasts during senescence (Chen and Chang, 1986, J. Cell. Physiol., 128:27-32.), it is unclear whether or not polyamine-dependent hypusine formation itself is an age-dependent biochemical event. In the present study, hypusine-forming activity was measured by a radiolabeling assay in cells whose polyamines have been depleted by prior treatment of alpha-difluoromethyl ornithine (DFMO). In addition, an in vitro cross-labeling assay was developed for simultaneous measurement of the deoxyhypusine synthase activity and protein substrate (elF-5A precursor) amount. We showed that the hypusine-forming activity in low-passage presenescent IMR-90 cells [population doubling level (PDL) = 15-23, termed young cells] was prominently induced by serum whereas little or no hypusine-forming activity could be detected in late-passage senescent cells (PDL = 46-54, termed old cells). The striking difference in hypusine-forming activity between young and old cells was due to changes in both deoxyhypusine synthase activity and elF-5A precursor amount in IMR-90 cells during senescence. However, Northern blot analysis showed no significant difference in the elF-5A messenger RNA (mRNA) between young and old cells, suggesting that the age-dependent attenuation of elF-5A precursor protein may be regulated at either translational or post-translational level.

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Hypusine, a new amino acid occurring in bovine brain

Cited by 108 publications

References 16 publications

Evaluation of the metal ion requirement of the human deoxyhypusine hydroxylase from HeLa cells using a novel enzyme assay

Evaluation of the metal ion requirement of the human deoxyhypusine hydroxylase from HeLa cells using a novel enzyme assay

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

Dramatic attenuation of hypusine formation on eukaryotic initiation factor 5A during senescence of IMR-90 human diploid fibroblasts

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