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
Drug Property Profile of Target
Target Poor or Non Binders
Target Regulators
Target Affiliated Biological Pathways
Target-Related Models and Studies
References
Drug Binding Sites of Target  Top
Ligand Name: Glutathione Ligand Info
Structure Description Crystal structure of PDZ1-2 from PSD-95 PDB:6SPV
Method X-ray diffraction Resolution 2.04 Å Mutation No [6]
PDB Sequence
EGEMEYEEIT
67
LERGNSGLGF
77
SIAGGTDNPH
87
IGDDPSIFIT
97
KIIPGGAAAQ
107

DGRLRVNDSI
117
LFVNEVDVRE
127
VTHSAAVEAL
137
KEAGSIVRLY
147
VMRRKPPAEK
157

VMEIKLIKGP
167
KGLGFSIAGG
177
VGNQHIPGDN
187
SIYVTKIIEG
197
GAAHKDGRLQ
207

IGDKILAVNS
217
VGLEDVMHED
227
AVAALKNTYD
237
VVYLKVAKP
Residue
Distance (Å)
GLU65
3.587
PHE119
3.708
ASN121
3.402
Residue
Distance (Å)
GLU122
2.914
ARG145
3.468
TYR147
3.750
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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
Protein Name Pfam ID Percentage of Identity (%) E value
Caspase recruitment domain-containing protein 11 (CARD11)
PF00619
30.000 (33/110) 8.28E-06
Regulating synaptic membrane exocytosis protein 2 (RIMS2)
PF00168 ; 
PF02318 ; 
PF17820
More >>
 35.065 (27/77) 3.00E-03
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
Hippo signaling pathway hsa04390 Affiliated Target
  Class: Environmental Information Processing => Signal transduction Pathway Hierarchy
Glutamatergic synapse hsa04724 Affiliated Target
  Class: Organismal Systems => Nervous system Pathway Hierarchy
Degree 69 Degree centrality 7.41E-03 Betweenness centrality 1.40E-02
Closeness centrality 2.51E-01 Radiality 1.44E+01 Clustering coefficient 2.77E-02
Neighborhood connectivity 1.44E+01 Topological coefficient 2.42E-02 Eccentricity 12
Download Click to Download the Full PPI Network of This Target

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