Target Information
| Target General Information | Top | |||||
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| Target ID |
T62265
(Former ID: TTDR00848)
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| Target Name |
Deoxyhypusine synthase (DHPS)
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| Synonyms |
DHS
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| Gene Name |
DHPS
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| Target Type |
Literature-reported target
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[1] | ||||
| Function |
Catalyzes the NAD-dependent oxidativecleavage of spermidine and the subsequent transfer of the butylamine moiety of spermidine to the epsilon-amino group of a specific lysine residue of the eIF-5A precursor protein to form the intermediate deoxyhypusine residue.
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| BioChemical Class |
Alkyl aryl transferase
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| UniProt ID | ||||||
| EC Number |
EC 2.5.1.46
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| Sequence |
MEGSLEREAPAGALAAVLKHSSTLPPESTQVRGYDFNRGVNYRALLEAFGTTGFQATNFG
RAVQQVNAMIEKKLEPLSQDEDQHADLTQSRRPLTSCTIFLGYTSNLISSGIRETIRYLV QHNMVDVLVTTAGGVEEDLIKCLAPTYLGEFSLRGKELRENGINRIGNLLVPNENYCKFE DWLMPILDQMVMEQNTEGVKWTPSKMIARLGKEINNPESVYYWAQKNHIPVFSPALTDGS LGDMIFFHSYKNPGLVLDIVEDLRLINTQAIFAKCTGMIILGGGVVKHHIANANLMRNGA DYAVYINTAQEFDGSDSGARPDEAVSWGKIRVDAQPVKVYADASLVFPLLVAETFAQKMD AFMHEKNED Click to Show/Hide
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| 3D Structure | Click to Show 3D Structure of This Target | PDB | ||||
| Cell-based Target Expression Variations | Top | |||||
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| Cell-based Target Expression Variations | ||||||
| Drug Binding Sites of Target | Top | |||||
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| Ligand Name: Spermidine | Ligand Info | |||||
| Structure Description | Crystal Structure of Human Deoxyhypusine Synthase in complex with spermidine and NAD | PDB:6XXJ | ||||
| Method | X-ray diffraction | Resolution | 1.41 Å | Mutation | No | [4] |
| PDB Sequence |
EAPAGALAAV
17 LKHSSTLPPE27 STQVRGYDFN37 RGVNYRALLE47 AFGTTGFQAT57 NFGRAVQQVN 67 AMIEKKLEPL77 SQDEDQHADL87 TQSRRPLTSC97 TIFLGYTSNL107 ISSGIRETIR 117 YLVQHNMVDV127 LVTTAGGVEE137 DLIKCLAPTY147 LGEFSLRGKE157 LRENGINRIG 167 NLLVPNENYK178 FEDWLMPILD188 QMVMEQNTEG198 VKWTPSKMIA208 RLGKEINNPE 218 SVYYWAQKNH228 IPVFSPALTD238 GSLGDMIFFH248 SYKNPGLVLD258 IVEDLRLINT 268 QAIFAKCTGM278 IILGGGVVKH288 HIANANLMRN298 GADYAVYINT308 AQEFDGSDSG 318 ARPDEAVSWG328 KIRVDAQPVK338 VYADASLVFP348 LLVAETFAQK358 MDAFM |
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| Click to View More Binding Site Information of This Target and Ligand Pair | ||||||
| Ligand Name: Nicotinamide-Adenine-Dinucleotide | Ligand Info | |||||
| Structure Description | Crystal Structure of Human Deoxyhypusine Synthase in complex with spermidine and NAD | PDB:6XXJ | ||||
| Method | X-ray diffraction | Resolution | 1.41 Å | Mutation | No | [4] |
| PDB Sequence |
EAPAGALAAV
17 LKHSSTLPPE27 STQVRGYDFN37 RGVNYRALLE47 AFGTTGFQAT57 NFGRAVQQVN 67 AMIEKKLEPL77 SQDEDQHADL87 TQSRRPLTSC97 TIFLGYTSNL107 ISSGIRETIR 117 YLVQHNMVDV127 LVTTAGGVEE137 DLIKCLAPTY147 LGEFSLRGKE157 LRENGINRIG 167 NLLVPNENYK178 FEDWLMPILD188 QMVMEQNTEG198 VKWTPSKMIA208 RLGKEINNPE 218 SVYYWAQKNH228 IPVFSPALTD238 GSLGDMIFFH248 SYKNPGLVLD258 IVEDLRLINT 268 QAIFAKCTGM278 IILGGGVVKH288 HIANANLMRN298 GADYAVYINT308 AQEFDGSDSG 318 ARPDEAVSWG328 KIRVDAQPVK338 VYADASLVFP348 LLVAETFAQK358 MDAFM |
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THR104
3.382
SER105
3.465
ASN106
2.864
LEU107
3.710
SER109
3.098
THR131
2.515
ALA132
3.100
GLY133
3.072
GLU136
3.504
GLU137
3.022
ILE166
3.956
ALA235
4.973
ASP238
2.502
GLY239
4.062
LEU281
4.971
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| Click to View More Binding Site Information of This Target and Ligand Pair | ||||||
| Click to View More Binding Site Information of This Target with Different Ligands | ||||||
| Different Human System Profiles of Target | Top |
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Human Similarity Proteins
of target is determined by comparing the sequence similarity of all human proteins with the target based on BLAST. The similarity proteins for a target are defined as the proteins with E-value < 0.005 and outside the protein families of the target.
A target that has fewer human similarity proteins outside its family is commonly regarded to possess a greater capacity to avoid undesired interactions and thus increase the possibility of finding successful drugs
(Brief Bioinform, 21: 649-662, 2020).
Human Tissue Distribution
of target is determined from a proteomics study that quantified more than 12,000 genes across 32 normal human tissues. Tissue Specificity (TS) score was used to define the enrichment of target across tissues.
The distribution of targets among different tissues or organs need to be taken into consideration when assessing the target druggability, as it is generally accepted that the wider the target distribution, the greater the concern over potential adverse effects
(Nat Rev Drug Discov, 20: 64-81, 2021).
Biological Network Descriptors
of target is determined based on a human protein-protein interactions (PPI) network consisting of 9,309 proteins and 52,713 PPIs, which were with a high confidence score of ≥ 0.95 collected from STRING database.
The network properties of targets based on protein-protein interactions (PPIs) have been widely adopted for the assessment of target’s druggability. Proteins with high node degree tend to have a high impact on network function through multiple interactions, while proteins with high betweenness centrality are regarded to be central for communication in interaction networks and regulate the flow of signaling information
(Front Pharmacol, 9, 1245, 2018;
Curr Opin Struct Biol. 44:134-142, 2017).
Human Similarity Proteins
Human Tissue Distribution
Biological Network Descriptors
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There is no similarity protein (E value < 0.005) for this target
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Note:
If a protein has TS (tissue specficity) scores at least in one tissue >= 2.5, this protein is called tissue-enriched (including tissue-enriched-but-not-specific and tissue-specific). In the plots, the vertical lines are at thresholds 2.5 and 4.
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| Degree | 3 | Degree centrality | 3.22E-04 | Betweenness centrality | 1.01E-04 |
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| Closeness centrality | 1.55E-01 | Radiality | 1.22E+01 | Clustering coefficient | 6.67E-01 |
| Neighborhood connectivity | 2.67E+00 | Topological coefficient | 6.67E-01 | Eccentricity | 14 |
| Download | Click to Download the Full PPI Network of This Target | ||||
| Chemical Structure based Activity Landscape of Target | Top |
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| Drug Property Profile of Target | Top | |
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| (1) Molecular Weight (mw) based Drug Clustering | (2) Octanol/Water Partition Coefficient (xlogp) based Drug Clustering | |
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| (3) Hydrogen Bond Donor Count (hbonddonor) based Drug Clustering | (4) Hydrogen Bond Acceptor Count (hbondacc) based Drug Clustering | |
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| (5) Rotatable Bond Count (rotbonds) based Drug Clustering | (6) Topological Polar Surface Area (polararea) based Drug Clustering | |
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| "RO5" indicates the cutoff set by lipinski's rule of five; "D123AB" colored in GREEN denotes the no violation of any cutoff in lipinski's rule of five; "D123AB" colored in PURPLE refers to the violation of only one cutoff in lipinski's rule of five; "D123AB" colored in BLACK represents the violation of more than one cutoffs in lipinski's rule of five | ||
| Target Regulators | Top | |||||
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| Target-interacting Proteins | ||||||
| Target Affiliated Biological Pathways | Top | |||||
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| BioCyc | [+] 1 BioCyc Pathways | + | ||||
| 1 | Hypusine biosynthesis | |||||
| NetPath Pathway | [+] 1 NetPath Pathways | + | ||||
| 1 | TGF_beta_Receptor Signaling Pathway | |||||
| WikiPathways | [+] 1 WikiPathways | + | ||||
| 1 | PTM: gamma carboxylation, hypusine formation and arylsulfatase activation | |||||
| Target-Related Models and Studies | Top | |||||
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| Target Validation | ||||||
| References | Top | |||||
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| REF 1 | How many drug targets are there Nat Rev Drug Discov. 2006 Dec;5(12):993-6. | |||||
| REF 2 | Effects of N1-guanyl-1,7-diaminoheptane, an inhibitor of deoxyhypusine synthase, on the growth of tumorigenic cell lines in culture. Biochim Biophys Acta. 1996 Jan 10;1310(1):119-26. | |||||
| REF 3 | Modification of eukaryotic initiation factor 5A from Plasmodium vivax by a truncated deoxyhypusine synthase from Plasmodium falciparum: An enzyme w... Bioorg Med Chem. 2007 Sep 15;15(18):6200-7. | |||||
| REF 4 | Half Way to Hypusine-Structural Basis for Substrate Recognition by Human Deoxyhypusine Synthase. Biomolecules. 2020 Mar 30;10(4):522. | |||||
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