2.5.1.46: deoxyhypusine synthase

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For detailed information about deoxyhypusine synthase, go to the full flat file.

Reaction

Synonyms

CpDHS, deoxyhypusine synthase, deoxyhypusine synthase (Caulobacter crescentus gene CC0359), deoxyhypusine synthase (Halobacterium strain NRC-1 gene dhs), deoxyhypusine synthase (human clone 30649 gene DHPS subunit reduced), deoxyhypusine synthase (Nicotiana tabacum gene DHS1), deoxyhypusine synthase (Senecio vernalis gene DHS1), deoxyhypusinesynthase, DHPS, DHS, DHS1, DHS2, DHS20, DHS34, DHSc, DHSp, DHYS, Dys1, Dys1p, EC 1.1.1.249, HVO 2297, PF3D7_1412600, speY, synthase, deoxyhypusine, TbDHSc, TbDHSp

ECTree

     2 Transferases

         2.5 Transferring alkyl or aryl groups, other than methyl groups

             2.5.1 Transferring alkyl or aryl groups, other than methyl groups (only sub-subclass identified to date)

                2.5.1.46 deoxyhypusine synthase

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Results	in table
3209	AA Sequence
7	Application
6	CAS Registry Number
35	Cloned(Commentary)
42	Cofactor
5	Crystallization (Commentary)
80	Disease/ Diagnostics
71	General Information
1	General Stability
2	IC50 Value
108	Inhibitors
22	Ki Value [mM]
40	KM Value [mM]
11	Localization
37	Molecular Weight [Da]
57	Natural Substrates/ Products (Substrates)
231	Organism
45	PDB ID
15	pH Optimum
3	pH Range
1	pI Value
3	Posttranslational Modification
57	Protein Variants
16	Purification (Commentary)
6	Reaction
1	Reaction Type
108	Reference
71	Source Tissue
14	Specific Activity [micromol/min/mg]
162	Substrates and Products (Substrate)
34	Subunits
84	Synonyms
1	Systematic Name
9	Temperature Optimum [°C]
1	Temperature Range [°C]
3	Temperature Stability [°C]
9	Turnover Number [1/s]

Application

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Application on EC 2.5.1.46 - deoxyhypusine synthase

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APPLICATION

ORGANISM

UNIPROT

COMMENTARY

LITERATURE

analysis

Homo sapiens

P49366

DHS activity can be determined by coupling the first phase reaction with the NADH-Glo assay in which the generation of luminescence is dependent on NADH derived from the DHS partial reaction. The non-radioactive DHS/NADH-Glo coupled assay is highly specific, sensitive and reproducible and can be configured for high throughput screening of small molecule libraries

758631

drug development

3 entries

medicine

3 entries

drug development

Fusarium graminearum

-

fungal DHS is a target for the development of inhibitors, for which CNI-1493 may serve as a lead substance

723229

drug development

Cryptosporidium parvum

A3FQA5

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

739026

drug development

Fusarium graminearum FG00323.1

-

fungal DHS is a target for the development of inhibitors, for which CNI-1493 may serve as a lead substance

-

medicine

Homo sapiens

P49366

elevated mRNA levels of the target enzymes deoxyhypusine synthase (DHPS) and ornithine decarboxylase (ODC) correlate with poor prognosis in a large cohort of neuroblastoma tumors. The DHPS inhibitor GC7 (N1-guanyl-1,7-diaminoheptane) and the ODC inhibitor alpha-difluoromethylornithine (DFMO) are target-specific and in combination induce synergistic effects in neuroblastomas at concentrations that are not individually cytotoxic. The drug combination induces caspase 3/7/9, but not caspase 8-mediated apoptosis, in neuroblastoma cells. Hypusinated eIF5A levels and intracellular spermidine levels correlate directly with drug treatments

758759

medicine

Mus musculus

Q3TXU5

in a transgenic mouse model of type 1 diabetes, in which human GAD65 is expressed in pancreatic beta-cells, and human MHC-II is expressed on antigen presenting cells, deoxyhypusine synthase inhibitor N''-guanyl-1,7-diaminoheptane, i.e. GC7, alters the pathophysiology by catalyzing the crucial hypusination and the rate-limiting step of elF5A activation. Inhibition of eIF5A resets the proinflammatory bias in the pancreatic microenvironment. There is reduction of Th1/Th17 response, an increase in Treg numbers, debase in IL17 and IL21 cytokines levels in serum, lowering of anti-GAD65 antibodies, and ablation of the ER stress that improves functionality of the beta-cells, but minimal effect on the cytotoxic CD8 T-cell mediated response

760180

medicine

Homo sapiens

P49366

recurrent missense variant p.Asn173Ser is identified with likely gene disrupting variant (c.1014+1G>A, c.912_917delTTACAT [p.Tyr305_Ile306del]), or c.1A>G [p.Met1?] in unrelated individuals having similar neurodevelopmental features that include global developmental delay and seizures. Two of four affected females have short stature. The c.1014+1G>A variant causes aberrant splicing. Recombinant p.Asn173Ser or p.Tyr305_Ile306del protein show reduced (20%) or absent in vitro activity, respectively. The p.Tyr305_Ile306del and p.Asn173Ser variants result in reduced hypusination of eIF5A compared to wild-type DHPS enzyme

758622