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 Affiliated Biological Pathways
Target-Related Models and Studies
References
Drug Binding Sites of Target  Top
Ligand Name: Cholesterol Ligand Info
Structure Description Cryo-EM structure of parathyroid hormone receptor type 1 in complex with a long-acting parathyroid hormone analog and G protein PDB:6NBF
Method Electron microscopy Resolution 3.00 Å Mutation Yes [4]
PDB Sequence
VMTKEEQIFL
40
LHRAQAQCEK
50
RLKEVGRPCL
109
PEWDHILCWP
119
LGAPGEVVAV
129

PCPDYIYDFN
139
HKGHAYRRCD
149
RNGSWELVPG
159
HNRTWANYSE
169
CVKFLTNETR
179

EREVFDRLAM
189
IYTVGYSVSL
199
ASLTVAVLIL
209
AYFRRLHCTR
219
NYIHMHLFLS
229

FMLRAVSIFV
239
KDAVLYSAGY
278
AGCRVAVTFF
288
LYFLATNYYW
298
ILVEGLYLHS
308

LIFMAFFSEK
318
KYLWGFTVFG
328
WGLPAVFVAV
338
WVSVRATLAN
348
TGCWDLSSGN
358

KKWIIQVPIL
368
ASIVLNFILF
378
INIVRVLATK
388
LRETNTRQQY
403
RKLLKSTLVL
413

MPLFGVHYIV
423
FMATPYTEVS
433
GTLWQVQMHY
443
EMLFNSFQGF
453
FVAIIYCFCN
463

GEVQAEIKKS
473
WSRWTLAL
Residue
Distance (Å)
HIS225
3.502
LEU232
3.927
ALA279
3.736
ARG282
3.599
VAL283
3.689
THR286
3.734
PHE287
3.665
TYR290
4.083
PHE291
3.798
TRP322
4.046
THR325
4.017
TRP329
3.562
ALA333
4.650
PHE335
4.039
VAL340
3.671
ASN348
4.805
TRP352
4.122
ASN358
3.263
LYS359
4.365
TRP361
3.609
Residue
Distance (Å)
ILE362
3.710
VAL365
4.156
PRO366
3.909
LEU368
3.657
ALA369
3.699
VAL372
4.394
PHE375
3.992
ILE422
3.498
VAL423
4.076
ALA426
3.257
THR427
3.776
PRO428
3.408
LEU436
4.053
GLN438
3.228
VAL439
3.653
HIS442
3.758
TYR443
4.083
LEU446
3.766
PHE447
3.663
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
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.
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KEGG Pathway Pathway ID Affiliated Target Pathway Map
Neuroactive ligand-receptor interaction hsa04080 Affiliated Target
  Class: Environmental Information Processing => Signaling molecules and interaction Pathway Hierarchy
Parathyroid hormone synthesis, secretion and action hsa04928 Affiliated Target
  Class: Organismal Systems => Endocrine system Pathway Hierarchy
Endocrine and other factor-regulated calcium reabsorption hsa04961 Affiliated Target
  Class: Organismal Systems => Excretory system Pathway Hierarchy
Degree 8 Degree centrality 8.59E-04 Betweenness centrality 7.98E-04
Closeness centrality 2.14E-01 Radiality 1.38E+01 Clustering coefficient 1.07E-01
Neighborhood connectivity 2.66E+01 Topological coefficient 1.45E-01 Eccentricity 12
Download Click to Download the Full PPI Network of This Target

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