Target Information

Target General Information

Target ID

T25317 (Former ID: TTDI02057)

Target Name

Cholestenol delta-isomerase (EBP)

Synonyms

Emopamilbinding protein; EBP; Delta(8)Delta(7) sterol isomerase; D8D7 sterol isomerase; 3betahydroxysteroidDelta(8),Delta(7)isomerase

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Gene Name

EBP

Target Type

Clinical trial target

[1]

Disease

[+] 1 Target-related Diseases

Rheumatoid arthritis [ICD-11: FA20]

Function

Catalyzes the conversion of Delta(8)-sterols to their corresponding Delta(7)-isomers.

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BioChemical Class

Intramolecular oxidoreductases

UniProt ID

EBP_HUMAN

EC Number

EC 5.3.3.5

Sequence

MTTNAGPLHPYWPQHLRLDNFVPNDRPTWHILAGLFSVTGVLVVTTWLLSGRAAVVPLGT
WRRLSLCWFAVCGFIHLVIEGWFVLYYEDLLGDQAFLSQLWKEYAKGDSRYILGDNFTVC
METITACLWGPLSLWVVIAFLRQHPLRFILQLVVSVGQIYGDVLYFLTEHRDGFQHGELG
HPLYFWFYFVFMNALWLVLPGVLVLDAVKHLTHAQSTLDAKATKAKSKKN

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3D Structure

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PDB

Drugs and Modes of Action

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Clinical Trial Drug(s)

[+] 1 Clinical Trial Drugs

SR-31747

Drug Info

Phase 2

Rheumatoid arthritis

[1]

Mode of Action

[+] 1 Modes of Action

Modulator

[+] 1 Modulator drugs

SR-31747

Drug Info

[1]

Cell-based Target Expression Variations

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Cell-based Target Expression Variations

Cell-based Target Expression Variations Info

Drug Binding Sites of Target

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Ligand Name: Tamoxifen

Ligand Info

Structure Description

Structure of EBP and tamoxifen

PDB:6OHU

Method

X-ray diffraction

Resolution

3.53 Å

Mutation

[2]

PDB Sequence

PLHPYWPQHL

¹⁶

RLDNFVPNDR

²⁶

PTWHILAGLF

³⁶

SVTGVLVVTT

⁴⁶

WLLSGRTWRR

⁶³

LSLCWFAVCG

⁷³

FIHLVIEGWF

⁸³

VLYYEDLLGD

⁹³

QAFLSQLWKE

¹⁰³

YAKGDSRYIL

¹¹³

GDNFTVCMET

¹²³

ITACLWGPLS

¹³³

LWVVIAFLRQ

¹⁴³

HPLRFILQLV

¹⁵³

VSVGQIYGDV

¹⁶³

LYFLTEHRDG

¹⁷³

FQHGELGHPL

¹⁸³

YFWFYFVFMN

¹⁹³

ALWLVLPGVL

²⁰³

VLDAVKHLTH

²¹³

AQSTLD

Residue

Distance (Å)

ILE31

4.749

LEU32

4.197

LEU35

3.475

PHE36

3.479

THR39

3.032

VAL71

4.449

PHE74

4.247

ILE75

3.340

ILE79

3.406

GLU80

3.170

LEU100

3.622

TRP101

3.690

Residue

Distance (Å)

GLU103

4.576

TYR104

4.017

TYR111

3.933

MET121

4.206

GLU122

4.219

ASP162

4.071

TYR165

3.908

PHE187

4.862

TYR188

3.198

MET192

3.563

ASN193

3.101

TRP196

3.518

Ligand Name: 3beta-(2-(Diethylamino)ethoxy)androst-5-en-17-one

Ligand Info

Structure Description

Structure of EBP and U18666A

PDB:6OHT

Method

X-ray diffraction

Resolution

3.20 Å

Mutation

[2]

PDB Sequence

PLHPYWPQHL

¹⁶

RLDNFVPNDR

²⁶

PTWHILAGLF

³⁶

SVTGVLVVTT

⁴⁶

WLLSGRTWRR

⁶³

LSLCWFAVCG

⁷³

FIHLVIEGWF

⁸³

VLYYEDLLGD

⁹³

QAFLSQLWKE

¹⁰³

YAKGDSRYIL

¹¹³

GDNFTVCETI

¹²⁴

TACLWGPLSL

¹³⁴

WVVIAFLRQH

¹⁴⁴

PLRFILQLVV

¹⁵⁴

SVGQIYGDVL

¹⁶⁴

YFLTEHRDGF

¹⁷⁴

QHGELGHPLY

¹⁸⁴

FWFYFVFNAL

¹⁹⁵

WLVLPGVLVL

²⁰⁵

DAVKHLTHAQ

²¹⁵

STLD

Residue

Distance (Å)

THR28

3.774

ILE31

3.327

LEU32

3.323

LEU35

3.974

ILE75

4.504

HIS76

4.595

ILE79

4.540

GLU80

3.380

LEU100

3.550

TRP101

4.135

GLU103

4.568

Residue

Distance (Å)

TYR104

3.628

TYR111

4.029

GLU122

4.190

GLY161

4.519

ASP162

3.150

TYR165

3.528

PHE187

3.543

TYR188

3.380

ASN193

3.108

TRP196

3.392

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

Different Human System Profiles of Target

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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).

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.

KEGG Pathway	Pathway ID	Affiliated Target	Pathway Map
Steroid biosynthesis	hsa00100	Affiliated Target
Class: Metabolism => Lipid metabolism	Pathway Hierarchy

Degree	3	Degree centrality	3.22E-04	Betweenness centrality	0.00E+00
Closeness centrality	1.85E-01	Radiality	1.31E+01	Clustering coefficient	1.00E+00
Neighborhood connectivity	9.33E+00	Topological coefficient	7.18E-01	Eccentricity	11
Download	Click to Download the Full PPI Network of This Target

Chemical Structure based Activity Landscape of Target

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Target Poor or Non Binders

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Target Poor or Non Binders

Target Poor or Non Binders Info

Target Profiles in Patients

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Target Expression
Profile (TEP)

Target Expression Profile Info

Target Affiliated Biological Pathways

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BioCyc

[+] 4 BioCyc Pathways

Cholesterol biosynthesis II (via 24,25-dihydrolanosterol)

Cholesterol biosynthesis III (via desmosterol)

Cholesterol biosynthesis I

Superpathway of cholesterol biosynthesis

KEGG Pathway

[+] 2 KEGG Pathways

Steroid biosynthesis

Metabolic pathways

References

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REF 1

Both the immunosuppressant SR31747 and the antiestrogen tamoxifen bind to an emopamil-insensitive site of mammalian Delta8-Delta7 sterol isomerase. J Pharmacol Exp Ther. 1998 Jun;285(3):1296-302.

REF 2

Structural basis for human sterol isomerase in cholesterol biosynthesis and multidrug recognition. Nat Commun. 2019 Jun 5;10(1):2452.

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