Target Information

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Target General Information
Drugs and Modes of Action
Drug Binding Sites of Target
Different Human System Profiles of Target
Chemical Structure based Activity Landscape of Target
Target Poor or Non Binders
References
Drug Binding Sites of Target  Top
Ligand Name: TAS-114 Ligand Info
Structure Description Crystal structure of Human dUTPase in complex with N-[(1R)-1-[3-(Cyclopentyloxy)-phenyl]-ethyl]-3-[(3,4-dihydro-2,4-dioxo-1(2H)-pyrimidinyl)methoxy]-1-propanesulfonamide PDB:5H4J
Method X-ray diffraction Resolution 1.80 Å Mutation No [2]
PDB Sequence
MQLRFARLSE
33
HATAPTRGSA
43
RAAGYDLYSA
53
YDYTIPPMEK
63
AVVKTDIQIA
73

LPSGCYGRVA
83
PRSGLAAKHF
93
IDVGAGVIDE
103
DYRGNVGVVL
113
FNFGKEKFEV
123

KKGDRIAQLI
133
CERIFYPEIE
143
EVQALD
Residue
Distance (Å)
VAL65
3.477
LYS67
3.916
VAL82
4.094
GLY97
4.238
ALA98
3.541
GLY99
2.905
VAL100
3.301
Residue
Distance (Å)
ILE101
3.818
TYR105
3.463
ASN108
3.526
VAL109
3.646
GLY110
2.702
VAL111
4.879
VAL112
3.432
Ligand Name: Deoxyuridine-5'-Diphosphate Ligand Info
Structure Description Human dUTP Pyrophosphatase complex with dUDP PDB:1Q5H
Method X-ray diffraction Resolution 2.00 Å Mutation No [3]
PDB Sequence
MQLRFARLSE
10
HATAPTRGSA
20
RAAGYDLYSA
30
YDYTIPPMEK
40
AVVKTDIQIA
50

LPSGCYGRVA
60
PRSGLAAKHF
70
IDVGAGVIDE
80
DYRGNVGVVL
90
FNFGKEKFEV
100

KKGDRIAQLI
110
CERIFYPEIE
120
EVQALDD
Residue
Distance (Å)
VAL59
4.458
GLY74
4.181
ALA75
3.532
GLY76
3.003
VAL77
3.418
ILE78
3.448
ASP79
2.802
Residue
Distance (Å)
TYR82
3.510
ASN85
3.730
VAL86
4.008
GLY87
2.725
VAL88
4.853
VAL89
4.402
Click to View More Binding Site Information of This Target with Different Ligands
Different Human System Profiles of Target  Top
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).
Human Pathway Affiliation of target is determined by the life-essential pathways provided on KEGG database. The target-affiliated pathways were defined based on the following two criteria (a) the pathways of the studied target should be life-essential for both healthy individuals and patients, and (b) the studied target should occupy an upstream position in the pathways and therefore had the ability to regulate biological function.
Targets involved in a fewer pathways have greater likelihood to be successfully developed, while those associated with more human pathways increase the chance of undesirable interferences with other human processes (Pharmacol Rev, 58: 259-279, 2006).
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
Human Pathway Affiliation
Biological Network Descriptors
There is no similarity protein (E value < 0.005) for this target
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.
 Download Picture         KEGG Link      
 Download Picture         KEGG Link      
KEGG Pathway Pathway ID Affiliated Target Pathway Map
Pyrimidine metabolism hsa00240 Affiliated Target
  Class: Metabolism => Nucleotide metabolism Pathway Hierarchy
Drug metabolism - other enzymes hsa00983 Affiliated Target
  Class: Metabolism => Xenobiotics biodegradation and metabolism Pathway Hierarchy
Degree 10 Degree centrality 1.07E-03 Betweenness centrality 1.02E-03
Closeness centrality 2.14E-01 Radiality 1.38E+01 Clustering coefficient 3.11E-01
Neighborhood connectivity 2.47E+01 Topological coefficient 1.41E-01 Eccentricity 11
Download Click to Download the Full PPI Network of This Target

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