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Literature summary for 1.14.99.29 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

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

Application

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

Cloned(Commentary)

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

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

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

Natural Substrates/ Products (Substrates)

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

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

Purification (Commentary)

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

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 and Products (Substrate)

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

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

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

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