Target Information

Target General Information

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Target ID

T42976

Target Name

Glutathione S-transferase A3 (GSTA3)

Synonyms

Glutathione S-transferase A3-3; GST class-alpha member 3

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Gene Name

GSTA3

Target Type

Literature-reported target

[1]

Function

Conjugation of reduced glutathione to a wide number of exogenous and endogenous hydrophobic electrophiles. Catalyzes isomerization reactions that contribute to the biosynthesis of steroid hormones. Efficiently catalyze obligatory double-bond isomerizations of delta(5)-androstene-3,17-dione and delta(5)-pregnene-3,20-dione, precursors to testosterone and progesterone, respectively.

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UniProt ID

GSTA3_HUMAN

EC Number

EC 2.5.1.18

Sequence

MAGKPKLHYFNGRGRMEPIRWLLAAAGVEFEEKFIGSAEDLGKLRNDGSLMFQQVPMVEI
DGMKLVQTRAILNYIASKYNLYGKDIKERALIDMYTEGMADLNEMILLLPLCRPEEKDAK
IALIKEKTKSRYFPAFEKVLQSHGQDYLVGNKLSRADISLVELLYYVEELDSSLISNFPL
LKALKTRISNLPTVKKFLQPGSPRKPPADAKALEEARKIFRF

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3D Structure

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PDB

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: Glutathione

Ligand Info

Structure Description

Glutathione transferase A3-3 in complex with glutathione and delta-4- androstene-3-17-dione

PDB:2VCV

Method

X-ray diffraction

Resolution

1.80 Å

Mutation

[2]

PDB Sequence

KPKLHYFNGR

¹³

GRMEPIRWLL

²³

AAAGVEFEEK

³³

FIGSAEDLGK

⁴³

LRNDGSLMFQ

⁵³

QVPMVEIDGM

⁶³

KLVQTRAILN

⁷³

YIASKYNLYG

⁸³

KDIKERALID

⁹³

MYTEGMADLN

¹⁰³

EMILLLPLCR

¹¹³

PEEKDAKIAL

¹²³

IKEKTKSRYF

¹³³

PAFEKVLQSH

¹⁴³

GQDYLVGNKL

¹⁵³

SRADISLVEL

¹⁶³

LYYVEELDSS

¹⁷³

LISNFPLLKA

¹⁸³

LKTRISNLPT

¹⁹³

VKKFLQPGSP

²⁰³

RKPPADAKAL

²¹³

EEARKIFRF

Residue

Distance (Å)

TYR9

2.988

ARG15

3.679

LEU41

4.689

ARG45

2.461

GLN53

4.206

GLN54

2.884

Residue

Distance (Å)

VAL55

2.762

PRO56

3.668

GLN67

2.633

THR68

3.022

ARG69

4.832

PHE220

3.644

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Ligand Name: 4-ANDROSTENE-3-17-DIONE

Ligand Info

Structure Description

Glutathione transferase A3-3 in complex with glutathione and delta-4- androstene-3-17-dione

PDB:2VCV

Method

X-ray diffraction

Resolution

1.80 Å

Mutation

[2]

PDB Sequence

KPKLHYFNGR

¹³

GRMEPIRWLL

²³

AAAGVEFEEK

³³

FIGSAEDLGK

⁴³

LRNDGSLMFQ

⁵³

QVPMVEIDGM

⁶³

KLVQTRAILN

⁷³

YIASKYNLYG

⁸³

KDIKERALID

⁹³

MYTEGMADLN

¹⁰³

EMILLLPLCR

¹¹³

PEEKDAKIAL

¹²³

IKEKTKSRYF

¹³³

PAFEKVLQSH

¹⁴³

GQDYLVGNKL

¹⁵³

SRADISLVEL

¹⁶³

LYYVEELDSS

¹⁷³

LISNFPLLKA

¹⁸³

LKTRISNLPT

¹⁹³

VKKFLQPGSP

²⁰³

RKPPADAKAL

²¹³

EEARKIFRF

Residue

Distance (Å)

TYR9

3.916

PHE10

3.664

GLY14

4.805

ARG15

4.468

LEU107

3.734

LEU108

4.156

PRO110

3.396

LEU111

4.006

Residue

Distance (Å)

ALA208

3.501

ASP209

4.705

ALA212

3.675

LEU213

3.623

ALA216

3.631

PHE220

3.880

PHE222

3.814

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). Human Similarity Proteins Human Tissue Distribution Human Pathway Affiliation

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).

Human Similarity Proteins

Human Tissue Distribution

Human Pathway Affiliation

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
Glutathione metabolism	hsa00480	Affiliated Target
Class: Metabolism => Metabolism of other amino acids	Pathway Hierarchy
Metabolism of xenobiotics by cytochrome P450	hsa00980	Affiliated Target
Class: Metabolism => Xenobiotics biodegradation and metabolism	Pathway Hierarchy
Drug metabolism - cytochrome P450	hsa00982	Affiliated Target
Class: Metabolism => Xenobiotics biodegradation and metabolism	Pathway Hierarchy
Drug metabolism - other enzymes	hsa00983	Affiliated Target
Class: Metabolism => Xenobiotics biodegradation and metabolism	Pathway Hierarchy

References

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REF 1

Glutathione-S-transferase A3 knockout mice are sensitive to acute cytotoxic and genotoxic effects of aflatoxin B1. Toxicol Appl Pharmacol. 2010 Feb 1;242(3):241-6.

REF 2

Structural basis for featuring of steroid isomerase activity in alpha class glutathione transferases. J Mol Biol. 2010 Mar 19;397(1):332-40.

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