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
Target Regulators
Target Affiliated Biological Pathways
References
Drug Binding Sites of Target  Top
Ligand Name: AZD-7545 Ligand Info
Structure Description Structure of pyruvate dehydrogenase kinase isoform 1 in complex with glucose-lowering drug AZD7545 PDB:2Q8G
Method X-ray diffraction Resolution 1.90 Å Mutation No [3]
PDB Sequence
GVPGQVDFYA
50
RFSPSPLSMK
60
QFLDFGSVNA
70
CEKTSFMFLR
80
QELPVRLANI
90

MKEISLLPDN
100
LLRTPSVQLV
110
QSWYIQSLQE
120
LLDFKDKSAE
130
DAKAIYDFTD
140

TVIRIRNRHN
150
DVIPTMAQGV
160
IEYKESFDPV
172
TSQNVQYFLD
182
RFYMSRISIR
192

MLLNQHSLLF
202
GKHIGSINPN
222
CNVLEVIKDG
232
YENARRLCDL
242
YYINSPELEL
252

EELNAKSPGQ
262
PIQVVYVPSH
272
LYHMVFELFK
282
NAMRATMEHH
292
ANRGVYPPIQ
302

VHVTLGNEDL
312
TVKMSDRGGG
322
VPLRKIDRLF
332
NYMYSTAPRP
342
RVETSRAVPL
352

AGFGYGLPIS
362
RLYAQYFQGD
372
LKLYSLEGYG
382
TDAVIYIKAL
392
STDSIERLPV
402

YNKAAWKHYN
412
TNDDWCVP
Residue
Distance (Å)
LEU57
3.737
GLN61
3.425
PHE62
3.236
ASP64
3.924
PHE65
3.426
THR74
3.416
SER75
2.500
PHE78
3.280
Residue
Distance (Å)
LEU79
3.534
MET193
4.591
LEU194
3.157
GLN197
2.972
HIS198
4.008
LEU201
3.919
PHE202
4.479
Ligand Name: Dichloroacetic acid Ligand Info
Structure Description Structure of pyruvate dehydrogenase kinase isoform 1 in complex with dichloroacetate (DCA) PDB:2Q8H
Method X-ray diffraction Resolution 2.00 Å Mutation No [3]
PDB Sequence
GVPGQVDFYA
50
RFSPSPLSMK
60
QFLDFGSCEK
73
TSFMFLRQEL
83
PVRLANIMKE
93

ISLLPDNLLR
103
TPSVQLVQSW
113
YIQSLQELLD
123
FKDKSAEDAK
133
AIYDFTDTVI
143

RIRNRHNDVI
153
PTMAQGVIEY
163
KESFDPVTSQ
175
NVQYFLDRFY
185
MSRISIRMLL
195

NQHSLLFGHI
216
GSINPNCNVL
226
EVIKDGYENA
236
RRLCDLYYIN
246
SPELELEELN
256

AKSPGQPIQV
266
VYVPSHLYHM
276
VFELFKNAMR
286
ATMEHHANRG
296
VYPPIQVHVT
306

LGNEDLTVKM
316
SDRGGGVPLR
326
KIDRLFNYMY
336
STAPRPRVET
346
SRAVPLAGFG
356

YGLPISRLYA
366
QYFQGDLKLY
376
SLEGYGTDAV
386
IYIKALSTDS
396
IERLPVYNKA
406

AWKHYNTNAD
418
DWCVP
Residue
Distance (Å)
LEU87
3.455
TYR114
3.146
SER117
4.519
ILE145
3.861
HIS149
4.230
VAL152
4.311
Residue
Distance (Å)
SER187
4.564
ARG188
2.798
ILE191
3.378
ARG192
3.987
LEU195
4.037
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      
KEGG Pathway Pathway ID Affiliated Target Pathway Map
HIF-1 signaling pathway hsa04066 Affiliated Target
  Class: Environmental Information Processing => Signal transduction Pathway Hierarchy
Degree 4 Degree centrality 4.30E-04 Betweenness centrality 0.00E+00
Closeness centrality 1.69E-01 Radiality 1.26E+01 Clustering coefficient 1.00E+00
Neighborhood connectivity 1.68E+01 Topological coefficient 6.20E-01 Eccentricity 13
Download Click to Download the Full PPI Network of This Target

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