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Literature summary extracted from

  • Kerscher, B.; Nzukou, E.; Kaiser, A.
    Assessment of deoxyhypusine hydroxylase as a putative, novel drug target (2010), Amino Acids, 38, 471-477.
    View publication on PubMed

Activating Compound

EC Number Activating Compound Comment Organism Structure
1.14.99.29 additional information the enzyme requires addition of sulfhydryl groups for catalytic activity Rattus norvegicus

Application

EC Number Application Comment Organism
1.14.99.29 drug development the parasite enzyme is a potential target for antimalaria drug design Plasmodium falciparum

Cloned(Commentary)

EC Number Cloned (Comment) Organism
1.14.99.29 gene dohh Plasmodium falciparum
1.14.99.29 gene dohh, cloned from a GST-ORF library in a biochemical genomics approach. The dohh gene complements a yeast deficient mutant YJR070C, expression as GST-tagged protein Saccharomyces cerevisiae
1.14.99.29 single copy gene dohh Bos taurus
1.14.99.29 single copy gene dohh, expression as GST-tagged protein, expression of the hypusine pathway genes in Escherichia coli as His-tagged proteins Homo sapiens

Inhibitors

EC Number Inhibitors Comment Organism Structure
1.14.99.29 2,2'-dipyridyl targets the active metalloenzyme and inhibits DOHH in human vascular endothelial cells Homo sapiens
1.14.99.29 alkyl 4-oxo-piperidine 3 carboxylates structurally related to dihydropyrimidines, most potent, putative DOHH inhibitors in vitro Plasmodium falciparum
1.14.99.29 ciclopirox targets the active metalloenzyme and inhibits DOHH in human vascular endothelial cells Homo sapiens
1.14.99.29 deferiprone targets the active metalloenzyme and inhibits DOHH in human vascular endothelial cells Homo sapiens
1.14.99.29 deferoxamine targets the active metalloenzyme and inhibits DOHH in human vascular endothelial cells Homo sapiens
1.14.99.29 mimosine targets the active metalloenzyme and inhibits DOHH in human vascular endothelial cells Homo sapiens
1.14.99.29 mimosine inhibits progression of cells from the G1 to S-phase by DOHH inhibition. DOHH reactivation occurs rapidly after inhibitor withdrawal and correlates with synchronized entry into the S-phase. Toxic in vivo Rattus norvegicus
1.14.99.29 additional information design of inhibitors against the human parasite enzyme from Plasmodium falciparum might profit from structural differences and the five HEAT-like repeats present in the parasite DOHH that differ in number and amino acid identity from its human orthologue, which contains four repeats Homo sapiens
1.14.99.29 additional information design of inhibitors against the parasite enzyme might profit from structural differences and the five HEAT-like repeats present in the parasite DOHH that differ in number and amino acid identity from its human orthologue, which contains four repeats. Compounds related structurally to dihydropyrimidines, like the plant amino acid mimosine and the antifungal drug ciclopiroxolamine, are toxic and/or not effective in vivo as anti-malarial drugs in rodents Plasmodium falciparum
1.14.99.29 additional information the active site is blocked by two catecholpeptides containing alpha 3,4-dihydroxybenzoyl- and alpha 2,3-dihydroxybenzoyl moiety. The 3,4-dihydroxybenzoyl-containing compound is more potent with a Ki of 32 mM Rattus norvegicus

Metals/Ions

EC Number Metals/Ions Comment Organism Structure
1.14.99.29 Fe2+ required, active site-bound Drosophila melanogaster
1.14.99.29 Fe2+ required, active site-bound Homo sapiens
1.14.99.29 Fe2+ required, active site-bound Rattus norvegicus
1.14.99.29 Fe2+ required, active site-bound Saccharomyces cerevisiae
1.14.99.29 Fe2+ required, active site-bound Bos taurus
1.14.99.29 Fe2+ required, active site-bound Schizosaccharomyces pombe
1.14.99.29 Fe2+ required, active site-bound Plasmodium falciparum

Molecular Weight [Da]

EC Number Molecular Weight [Da] Molecular Weight Maximum [Da] Comment Organism
1.14.99.29 42000
-
 x * 42000, SDS-PAGE Plasmodium falciparum

Natural Substrates/ Products (Substrates)

EC Number Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
1.14.99.29 eIF5A-N6-(4-aminobutyl)-L-lysine + AH2 + O2 Drosophila melanogaster
-
 eIF5A-N6-(4-amino-2-hydroxybutyl)-L-lysine + A + H2O
-
 ?
1.14.99.29 eIF5A-N6-(4-aminobutyl)-L-lysine + AH2 + O2 Homo sapiens
-
 eIF5A-N6-(4-amino-2-hydroxybutyl)-L-lysine + A + H2O
-
 ?
1.14.99.29 eIF5A-N6-(4-aminobutyl)-L-lysine + AH2 + O2 Rattus norvegicus
-
 eIF5A-N6-(4-amino-2-hydroxybutyl)-L-lysine + A + H2O
-
 ?
1.14.99.29 eIF5A-N6-(4-aminobutyl)-L-lysine + AH2 + O2 Saccharomyces cerevisiae
-
 eIF5A-N6-(4-amino-2-hydroxybutyl)-L-lysine + A + H2O
-
 ?
1.14.99.29 eIF5A-N6-(4-aminobutyl)-L-lysine + AH2 + O2 Bos taurus
-
 eIF5A-N6-(4-amino-2-hydroxybutyl)-L-lysine + A + H2O
-
 ?
1.14.99.29 eIF5A-N6-(4-aminobutyl)-L-lysine + AH2 + O2 Schizosaccharomyces pombe
-
 eIF5A-N6-(4-amino-2-hydroxybutyl)-L-lysine + A + H2O
-
 ?
1.14.99.29 eIF5A-N6-(4-aminobutyl)-L-lysine + AH2 + O2 Plasmodium falciparum
-
 eIF5A-N6-(4-amino-2-hydroxybutyl)-L-lysine + A + H2O
-
 ?

Organism

EC Number Organism UniProt Comment Textmining
1.14.99.29 Bos taurus
-
-
-
1.14.99.29 Drosophila melanogaster
-
-
-
1.14.99.29 Homo sapiens
-
-
-
1.14.99.29 Plasmodium falciparum
-
-
-
1.14.99.29 Rattus norvegicus
-
-
-
1.14.99.29 Saccharomyces cerevisiae
-
-
-
1.14.99.29 Schizosaccharomyces pombe
-
-
-

Purification (Commentary)

EC Number Purification (Comment) Organism
1.14.99.29 native enzyme is partially purified from testis Rattus norvegicus
1.14.99.29 native plasmodial DOHH by anion exchange chromatography and nickel affinity chromatography Plasmodium falciparum
1.14.99.29 recombinant GST-tagged DOHH by glutathione affinity chromatography Saccharomyces cerevisiae
1.14.99.29 recombinant GST-tagged DOHH by glutathione affinity chromatography. Recombinant His-tagged hypusine pathway enzymes from Escherichia coli by anion exchange and nickel affinity chromatography Homo sapiens

Source Tissue

EC Number Source Tissue Comment Organism Textmining
1.14.99.29 brain expression at different developmental stages, highest specific activities of DOHH occur in the parietal cortex during the first 5 days of life. After this period, DOHH activity declines to less than 50% of the level in the newborn within 15 days Rattus norvegicus
-
1.14.99.29 testis
-
 Rattus norvegicus
-

Substrates and Products (Substrate)

EC Number Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
1.14.99.29 eIF5A-N6-(4-aminobutyl)-L-lysine + AH2 + O2
-
 Drosophila melanogaster eIF5A-N6-(4-amino-2-hydroxybutyl)-L-lysine + A + H2O
-
 ?
1.14.99.29 eIF5A-N6-(4-aminobutyl)-L-lysine + AH2 + O2
-
 Homo sapiens eIF5A-N6-(4-amino-2-hydroxybutyl)-L-lysine + A + H2O
-
 ?
1.14.99.29 eIF5A-N6-(4-aminobutyl)-L-lysine + AH2 + O2
-
 Rattus norvegicus eIF5A-N6-(4-amino-2-hydroxybutyl)-L-lysine + A + H2O
-
 ?
1.14.99.29 eIF5A-N6-(4-aminobutyl)-L-lysine + AH2 + O2
-
 Saccharomyces cerevisiae eIF5A-N6-(4-amino-2-hydroxybutyl)-L-lysine + A + H2O
-
 ?
1.14.99.29 eIF5A-N6-(4-aminobutyl)-L-lysine + AH2 + O2
-
 Bos taurus eIF5A-N6-(4-amino-2-hydroxybutyl)-L-lysine + A + H2O
-
 ?
1.14.99.29 eIF5A-N6-(4-aminobutyl)-L-lysine + AH2 + O2
-
 Schizosaccharomyces pombe eIF5A-N6-(4-amino-2-hydroxybutyl)-L-lysine + A + H2O
-
 ?
1.14.99.29 eIF5A-N6-(4-aminobutyl)-L-lysine + AH2 + O2
-
 Plasmodium falciparum eIF5A-N6-(4-amino-2-hydroxybutyl)-L-lysine + A + H2O
-
 ?
1.14.99.29 additional information purified DOHH protein displays no phycocyanin lyase activity Plasmodium falciparum ?
-
 ?

Subunits

EC Number Subunits Comment Organism
1.14.99.29 ? x * 42000, SDS-PAGE Plasmodium falciparum
1.14.99.29 More DOHHs from different species differ in their HEAT-like repeats Drosophila melanogaster
1.14.99.29 More DOHHs from different species differ in their HEAT-like repeats Homo sapiens
1.14.99.29 More DOHHs from different species differ in their HEAT-like repeats Rattus norvegicus
1.14.99.29 More DOHHs from different species differ in their HEAT-like repeats Saccharomyces cerevisiae
1.14.99.29 More DOHHs from different species differ in their HEAT-like repeats Bos taurus
1.14.99.29 More DOHHs from different species differ in their HEAT-like repeats Schizosaccharomyces pombe
1.14.99.29 More DOHHs from different species differ in their HEAT-like repeats Plasmodium falciparum

Synonyms

EC Number Synonyms Comment Organism
1.14.99.29 deoxyhypusine hydroxylase
-
 Drosophila melanogaster
1.14.99.29 deoxyhypusine hydroxylase
-
 Homo sapiens
1.14.99.29 deoxyhypusine hydroxylase
-
 Rattus norvegicus
1.14.99.29 deoxyhypusine hydroxylase
-
 Saccharomyces cerevisiae
1.14.99.29 deoxyhypusine hydroxylase
-
 Bos taurus
1.14.99.29 deoxyhypusine hydroxylase
-
 Schizosaccharomyces pombe
1.14.99.29 deoxyhypusine hydroxylase
-
 Plasmodium falciparum
1.14.99.29 DOHH
-
 Drosophila melanogaster
1.14.99.29 DOHH
-
 Homo sapiens
1.14.99.29 DOHH
-
 Rattus norvegicus
1.14.99.29 DOHH
-
 Saccharomyces cerevisiae
1.14.99.29 DOHH
-
 Bos taurus
1.14.99.29 DOHH
-
 Schizosaccharomyces pombe
1.14.99.29 DOHH
-
 Plasmodium falciparum
1.14.99.29 More DOHH belongs to a family of HEAT-like repeat proteins which comprise the Huntingtin protein, elongation factor 3, the protein phosphatase subunit 2A, and the target of rapamycin Homo sapiens
1.14.99.29 More DOHH belongs to a family of HEAT-like repeat proteins which comprise the Huntingtin protein, elongation factor 3, the protein phosphatase subunit 2A, and the target of rapamycin Saccharomyces cerevisiae
1.14.99.29 More DOHH belongs to a family of HEAT-like repeat proteins which comprise the Huntingtin protein, elongation factor 3, the protein phosphatase subunit 2A, and the target of rapamycin Bos taurus
1.14.99.29 More DOHH belongs to a family of HEAT-like repeat proteins which comprise the Huntingtin protein, elongation factor 3, the protein phosphatase subunit 2A, and the target of rapamycin Plasmodium falciparum

General Information

EC Number General Information Comment Organism
1.14.99.29 evolution Plasmodium falciparum DOHH arose from an originally from an EF/type cyanobacterial phycobilin lyase by loss of function. It has a low FASTA score of 27 to its human counterpart Plasmodium falciparum
1.14.99.29 malfunction a mutated deoxyhypusine hydroxylase gene nero affects cell and organ size. However, nero is not required for cell viability. Loss of eIF5A causes phenotypes highly similar to nero but more severe than nero. Inhibition of Nero or eIF5A by RNAi causes a similar impairment in translation elongation Drosophila melanogaster
1.14.99.29 malfunction a mutation in the dohh gene causes defects in mitochondrial morphology, distribution and displayed synthetic defects in growth Schizosaccharomyces pombe
1.14.99.29 metabolism biosynthesis of hypusine occurs in two consecutive steps. In the first step, deoxyhypusine synthase transfers the 4-aminobutyl moiety to a specific lysine residue in eIF5A, while in the second step of hypusine biosynthesis, deoxyhypusine hydroxylase completes this posttranslational modification by hydroxylation Drosophila melanogaster
1.14.99.29 metabolism biosynthesis of hypusine occurs in two consecutive steps. In the first step, deoxyhypusine synthase transfers the 4-aminobutyl moiety to a specific lysine residue in eIF5A, while in the second step of hypusine biosynthesis, deoxyhypusine hydroxylase completes this posttranslational modification by hydroxylation Homo sapiens
1.14.99.29 metabolism biosynthesis of hypusine occurs in two consecutive steps. In the first step, deoxyhypusine synthase transfers the 4-aminobutyl moiety to a specific lysine residue in eIF5A, while in the second step of hypusine biosynthesis, deoxyhypusine hydroxylase completes this posttranslational modification by hydroxylation Rattus norvegicus
1.14.99.29 metabolism biosynthesis of hypusine occurs in two consecutive steps. In the first step, deoxyhypusine synthase transfers the 4-aminobutyl moiety to a specific lysine residue in eIF5A, while in the second step of hypusine biosynthesis, deoxyhypusine hydroxylase completes this posttranslational modification by hydroxylation Saccharomyces cerevisiae
1.14.99.29 metabolism biosynthesis of hypusine occurs in two consecutive steps. In the first step, deoxyhypusine synthase transfers the 4-aminobutyl moiety to a specific lysine residue in eIF5A, while in the second step of hypusine biosynthesis, deoxyhypusine hydroxylase completes this posttranslational modification by hydroxylation Bos taurus
1.14.99.29 metabolism biosynthesis of hypusine occurs in two consecutive steps. In the first step, deoxyhypusine synthase transfers the 4-aminobutyl moiety to a specific lysine residue in eIF5A, while in the second step of hypusine biosynthesis, deoxyhypusine hydroxylase completes this posttranslational modification by hydroxylation Schizosaccharomyces pombe
1.14.99.29 metabolism biosynthesis of hypusine occurs in two consecutive steps. In the first step, deoxyhypusine synthase transfers the 4-aminobutyl moiety to a specific lysine residue in eIF5A, while in the second step of hypusine biosynthesis, deoxyhypusine hydroxylase completes this posttranslational modification by hydroxylation Plasmodium falciparum
1.14.99.29 additional information antiretroviral effects of alpha-hydroxypyridones (i.e. mimosine and deferiprone) on HIV-1 multiplication in T-lymphocytic and promonocytic cell lines through deoxyhypusine hydroxylase inhibition Homo sapiens
1.14.99.29 physiological function deoxyhypusine hydroxylase completes the modification of eukaryotic initiation factor 5A, eIF5A, through hydroxylation. Hypusination in eIF5A is a unique posttranslational modification. Hypusine-containing eIF5A promotes translation elongation Homo sapiens
1.14.99.29 physiological function deoxyhypusine hydroxylase completes the modification of eukaryotic initiation factor 5A, eIF5A, through hydroxylation. Hypusination in eIF5A is a unique posttranslational modification. Hypusine-containing eIF5A promotes translation elongation Rattus norvegicus
1.14.99.29 physiological function deoxyhypusine hydroxylase completes the modification of eukaryotic initiation factor 5A, eIF5A, through hydroxylation. Hypusination in eIF5A is a unique posttranslational modification. Hypusine-containing eIF5A promotes translation elongation Bos taurus
1.14.99.29 physiological function deoxyhypusine hydroxylase completes the modification of eukaryotic initiation factor 5A, eIF5A, through hydroxylation. Hypusination in eIF5A is a unique posttranslational modification. Hypusine-containing eIF5A promotes translation elongation Plasmodium falciparum
1.14.99.29 physiological function deoxyhypusine hydroxylase completes the modification of eukaryotic initiation factor 5A, eIF5A, through hydroxylation. Hypusination in eIF5A is a unique posttranslational modification. Hypusine-containing eIF5A promotes translation elongation. Deoxyhypusinated eIF5A intermediate can fulfill the function of the hypusinated eIF5A in yeast Saccharomyces cerevisiae
1.14.99.29 physiological function deoxyhypusine hydroxylase completes the modification of eukaryotic initiation factor 5A, eIF5A, through hydroxylation. Hypusination in eIF5A is a unique posttranslational modification. Hypusine-containing eIF5A promotes translation elongation. The homologous dohh gene and its target eIF5A are required for cell growth and the regulation of autophagy. The Nero protein regulates eIF5A activity, eIF5A is upregulated in nero mutants Drosophila melanogaster
1.14.99.29 physiological function DOHH is required for the alignment of mitochondria along microtubules. Deoxyhypusine hydroxylase completes the modification of eukaryotic initiation factor 5A, eIF5A, through hydroxylation. Hypusination in eIF5A is a unique posttranslational modification. Hypusine-containing eIF5A promotes translation elongation Schizosaccharomyces pombe