Activating Compound | Comment | Organism | Structure |
---|---|---|---|
additional information | the enzyme requires addition of sulfhydryl groups for catalytic activity | Rattus norvegicus |
Application | Comment | Organism |
---|---|---|
drug development | the parasite enzyme is a potential target for antimalaria drug design | Plasmodium falciparum |
Cloned (Comment) | Organism |
---|---|
gene dohh | Plasmodium falciparum |
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 |
single copy gene dohh | Bos taurus |
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 | Comment | Organism | Structure |
---|---|---|---|
2,2'-dipyridyl | targets the active metalloenzyme and inhibits DOHH in human vascular endothelial cells | Homo sapiens | |
alkyl 4-oxo-piperidine 3 carboxylates | structurally related to dihydropyrimidines, most potent, putative DOHH inhibitors in vitro | Plasmodium falciparum | |
ciclopirox | targets the active metalloenzyme and inhibits DOHH in human vascular endothelial cells | Homo sapiens | |
deferiprone | targets the active metalloenzyme and inhibits DOHH in human vascular endothelial cells | Homo sapiens | |
deferoxamine | targets the active metalloenzyme and inhibits DOHH in human vascular endothelial cells | Homo sapiens | |
mimosine | targets the active metalloenzyme and inhibits DOHH in human vascular endothelial cells | Homo sapiens | |
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 | |
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 | |
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 | |
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 | Comment | Organism | Structure |
---|---|---|---|
Fe2+ | required, active site-bound | Drosophila melanogaster | |
Fe2+ | required, active site-bound | Homo sapiens | |
Fe2+ | required, active site-bound | Rattus norvegicus | |
Fe2+ | required, active site-bound | Saccharomyces cerevisiae | |
Fe2+ | required, active site-bound | Bos taurus | |
Fe2+ | required, active site-bound | Schizosaccharomyces pombe | |
Fe2+ | required, active site-bound | Plasmodium falciparum |
Molecular Weight [Da] | Molecular Weight Maximum [Da] | Comment | Organism |
---|---|---|---|
42000 | - |
x * 42000, SDS-PAGE | Plasmodium falciparum |
Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
---|---|---|---|---|---|---|
eIF5A-N6-(4-aminobutyl)-L-lysine + AH2 + O2 | Drosophila melanogaster | - |
eIF5A-N6-(4-amino-2-hydroxybutyl)-L-lysine + A + H2O | - |
? | |
eIF5A-N6-(4-aminobutyl)-L-lysine + AH2 + O2 | Homo sapiens | - |
eIF5A-N6-(4-amino-2-hydroxybutyl)-L-lysine + A + H2O | - |
? | |
eIF5A-N6-(4-aminobutyl)-L-lysine + AH2 + O2 | Rattus norvegicus | - |
eIF5A-N6-(4-amino-2-hydroxybutyl)-L-lysine + A + H2O | - |
? | |
eIF5A-N6-(4-aminobutyl)-L-lysine + AH2 + O2 | Saccharomyces cerevisiae | - |
eIF5A-N6-(4-amino-2-hydroxybutyl)-L-lysine + A + H2O | - |
? | |
eIF5A-N6-(4-aminobutyl)-L-lysine + AH2 + O2 | Bos taurus | - |
eIF5A-N6-(4-amino-2-hydroxybutyl)-L-lysine + A + H2O | - |
? | |
eIF5A-N6-(4-aminobutyl)-L-lysine + AH2 + O2 | Schizosaccharomyces pombe | - |
eIF5A-N6-(4-amino-2-hydroxybutyl)-L-lysine + A + H2O | - |
? | |
eIF5A-N6-(4-aminobutyl)-L-lysine + AH2 + O2 | Plasmodium falciparum | - |
eIF5A-N6-(4-amino-2-hydroxybutyl)-L-lysine + A + H2O | - |
? |
Organism | UniProt | Comment | Textmining |
---|---|---|---|
Bos taurus | - |
- |
- |
Drosophila melanogaster | - |
- |
- |
Homo sapiens | - |
- |
- |
Plasmodium falciparum | - |
- |
- |
Rattus norvegicus | - |
- |
- |
Saccharomyces cerevisiae | - |
- |
- |
Schizosaccharomyces pombe | - |
- |
- |
Purification (Comment) | Organism |
---|---|
native enzyme is partially purified from testis | Rattus norvegicus |
native plasmodial DOHH by anion exchange chromatography and nickel affinity chromatography | Plasmodium falciparum |
recombinant GST-tagged DOHH by glutathione affinity chromatography | Saccharomyces cerevisiae |
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 | Comment | Organism | Textmining |
---|---|---|---|
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 | - |
testis | - |
Rattus norvegicus | - |
Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
---|---|---|---|---|---|---|
eIF5A-N6-(4-aminobutyl)-L-lysine + AH2 + O2 | - |
Drosophila melanogaster | eIF5A-N6-(4-amino-2-hydroxybutyl)-L-lysine + A + H2O | - |
? | |
eIF5A-N6-(4-aminobutyl)-L-lysine + AH2 + O2 | - |
Homo sapiens | eIF5A-N6-(4-amino-2-hydroxybutyl)-L-lysine + A + H2O | - |
? | |
eIF5A-N6-(4-aminobutyl)-L-lysine + AH2 + O2 | - |
Rattus norvegicus | eIF5A-N6-(4-amino-2-hydroxybutyl)-L-lysine + A + H2O | - |
? | |
eIF5A-N6-(4-aminobutyl)-L-lysine + AH2 + O2 | - |
Saccharomyces cerevisiae | eIF5A-N6-(4-amino-2-hydroxybutyl)-L-lysine + A + H2O | - |
? | |
eIF5A-N6-(4-aminobutyl)-L-lysine + AH2 + O2 | - |
Bos taurus | eIF5A-N6-(4-amino-2-hydroxybutyl)-L-lysine + A + H2O | - |
? | |
eIF5A-N6-(4-aminobutyl)-L-lysine + AH2 + O2 | - |
Schizosaccharomyces pombe | eIF5A-N6-(4-amino-2-hydroxybutyl)-L-lysine + A + H2O | - |
? | |
eIF5A-N6-(4-aminobutyl)-L-lysine + AH2 + O2 | - |
Plasmodium falciparum | eIF5A-N6-(4-amino-2-hydroxybutyl)-L-lysine + A + H2O | - |
? | |
additional information | purified DOHH protein displays no phycocyanin lyase activity | Plasmodium falciparum | ? | - |
? |
Subunits | Comment | Organism |
---|---|---|
? | x * 42000, SDS-PAGE | Plasmodium falciparum |
More | DOHHs from different species differ in their HEAT-like repeats | Drosophila melanogaster |
More | DOHHs from different species differ in their HEAT-like repeats | Homo sapiens |
More | DOHHs from different species differ in their HEAT-like repeats | Rattus norvegicus |
More | DOHHs from different species differ in their HEAT-like repeats | Saccharomyces cerevisiae |
More | DOHHs from different species differ in their HEAT-like repeats | Bos taurus |
More | DOHHs from different species differ in their HEAT-like repeats | Schizosaccharomyces pombe |
More | DOHHs from different species differ in their HEAT-like repeats | Plasmodium falciparum |
Synonyms | Comment | Organism |
---|---|---|
deoxyhypusine hydroxylase | - |
Drosophila melanogaster |
deoxyhypusine hydroxylase | - |
Homo sapiens |
deoxyhypusine hydroxylase | - |
Rattus norvegicus |
deoxyhypusine hydroxylase | - |
Saccharomyces cerevisiae |
deoxyhypusine hydroxylase | - |
Bos taurus |
deoxyhypusine hydroxylase | - |
Schizosaccharomyces pombe |
deoxyhypusine hydroxylase | - |
Plasmodium falciparum |
DOHH | - |
Drosophila melanogaster |
DOHH | - |
Homo sapiens |
DOHH | - |
Rattus norvegicus |
DOHH | - |
Saccharomyces cerevisiae |
DOHH | - |
Bos taurus |
DOHH | - |
Schizosaccharomyces pombe |
DOHH | - |
Plasmodium falciparum |
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 |
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 |
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 |
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 | Comment | Organism |
---|---|---|
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 |
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 |
malfunction | a mutation in the dohh gene causes defects in mitochondrial morphology, distribution and displayed synthetic defects in growth | Schizosaccharomyces pombe |
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 |
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 |
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 |
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 |
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 |
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 |
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 |
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 |
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 |
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 |
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 |
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 |
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 |
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 |
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 |