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Literature summary for 2.5.1.46 extracted from

  • Mittal, N.; Morada, M.; Tripathi, P.; Gowri, V.S.; Mandal, S.; Quirch, A.; Park, M.H.; Yarlett, N.; Madhubala, R.
    Cryptosporidium parvum has an active hypusine biosynthesis pathway (2014), Mol. Biochem. Parasitol., 195, 14-22.
    View publication on PubMedView publication on EuropePMC

Application

Application Comment Organism
drug development Cryptosporidium parvum DHS is a traget for drug development, as GC7 effectively inhibits parasite infection and growth in cultured host cells Cryptosporidium parvum

Cloned(Commentary)

Cloned (Comment) Organism
gene DHS, DNA and amino acid sequence determination and analysis, sequence comparisons and phylogenetic analysis, recombinant expression of His-tagged enzyme in Escherichia coli strain BL21(DE3) Cryptosporidium parvum

Inhibitors

Inhibitors Comment Organism Structure
1,8-diaminooctane weaker inhibition Cryptosporidium parvum
diaminononane weaker inhibition Cryptosporidium parvum
N1-guanyl-1,7-diaminoheptane GC7, a potent competitive inhibitor of DHS, causes an effective inhibition of infection and growth of Cryptosporidium parvum in human HCT-8 adenocarcinoma cells. Complete inhibition at 0.01 mM Cryptosporidium parvum
paromomycin inhibits oocysts formation Cryptosporidium parvum

KM Value [mM]

KM Value [mM] KM Value Maximum [mM] Substrate Comment Organism Structure
0.00091
-
[eIF5A-precursor]-lysine pH 7.5, 37°C, heterotetrameric DHS Cryptosporidium parvum
0.0123
-
spermidine pH 7.5, 37°C, heterotetrameric DHS Cryptosporidium parvum

Molecular Weight [Da]

Molecular Weight [Da] Molecular Weight Maximum [Da] Comment Organism
40800
-
-
Cryptosporidium parvum
180000
-
native PAGE Cryptosporidium parvum

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
[eIF5A-precursor]-lysine + spermidine Cryptosporidium parvum
-
[eIF5A-precursor]-deoxyhypusine + propane-1,3-diamine
-
?

Organism

Organism UniProt Comment Textmining
Cryptosporidium parvum A3FQA5 single-copy gene DHS
-

Purification (Commentary)

Purification (Comment) Organism
recombinant His-tagged enzyme from Escherichia coli strain BL21(DE3) to homogeneity by nickel affinity chromatography Cryptosporidium parvum

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
[eIF5A-precursor]-lysine + spermidine
-
Cryptosporidium parvum [eIF5A-precursor]-deoxyhypusine + propane-1,3-diamine
-
?

Subunits

Subunits Comment Organism
tetramer 4 * 40800, about, sequence calculation Cryptosporidium parvum

Synonyms

Synonyms Comment Organism
CpDHS
-
Cryptosporidium parvum
DHS
-
Cryptosporidium parvum

Temperature Optimum [°C]

Temperature Optimum [°C] Temperature Optimum Maximum [°C] Comment Organism
37
-
assay at Cryptosporidium parvum

pH Optimum

pH Optimum Minimum pH Optimum Maximum Comment Organism
9.2
-
assay at Cryptosporidium parvum

Cofactor

Cofactor Comment Organism Structure
NAD+ required Cryptosporidium parvum

Ki Value [mM]

Ki Value [mM] Ki Value maximum [mM] Inhibitor Comment Organism Structure
additional information
-
additional information inhibition profile in a series of kinetic experiments Cryptosporidium parvum

General Information

General Information Comment Organism
evolution CpDHS is more closely related to apicomplexan and human DHS than to kinetoplast DHS Cryptosporidium parvum
additional information enzyme structure modelling, model evaluation and comparative structural analysis, overview Cryptosporidium parvum
physiological function hypusination of eIF5A is an important post-translational modification essential for cell proliferation. This modification occurs in a two step processcatalyzed by deoxyhypusine synthase followed by deoxyhypusine hydroxylase Cryptosporidium parvum