Target Information
| Target General Information | Top | |||||
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| Target ID |
T69420
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| Target Name |
Glutathione synthetase (GSS)
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| Synonyms |
Glutathione synthase; GSH-S; GSH synthetase
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| Gene Name |
GSS
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| Target Type |
Literature-reported target
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[1] | ||||
| Function |
Catalyzes the oxidation of GSH to glutathione disulfide (GSSG) by reducing free radicals and reactive oxygen species such as hydrogen peroxide. Uses GSH to clean up various metabolites, xenobiotics, and electrophiles to mercapturates for excretion.
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| UniProt ID | ||||||
| EC Number |
EC 6.3.2.3
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| Sequence |
MATNWGSLLQDKQQLEELARQAVDRALAEGVLLRTSQEPTSSEVVSYAPFTLFPSLVPSA
LLEQAYAVQMDFNLLVDAVSQNAAFLEQTLSSTIKQDDFTARLFDIHKQVLKEGIAQTVF LGLNRSDYMFQRSADGSPALKQIEINTISASFGGLASRTPAVHRHVLSVLSKTKEAGKIL SNNPSKGLALGIAKAWELYGSPNALVLLIAQEKERNIFDQRAIENELLARNIHVIRRTFE DISEKGSLDQDRRLFVDGQEIAVVYFRDGYMPRQYSLQNWEARLLLERSHAAKCPDIATQ LAGTKKVQQELSRPGMLEMLLPGQPEAVARLRATFAGLYSLDVGEEGDQAIAEALAAPSR FVLKPQREGGGNNLYGEEMVQALKQLKDSEERASYILMEKIEPEPFENCLLRPGSPARVV QCISELGIFGVYVRQEKTLVMNKHVGHLLRTKAIEHADGGVAAGVAVLDNPYPV Click to Show/Hide
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| 3D Structure | Click to Show 3D Structure of This Target | PDB | ||||
| HIT2.0 ID | T80U0C | |||||
| Cell-based Target Expression Variations | Top | |||||
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| Cell-based Target Expression Variations | ||||||
| Drug Binding Sites of Target | Top | |||||
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| Ligand Name: Glutathione | Ligand Info | |||||
| Structure Description | HUMAN GLUTATHIONE SYNTHETASE | PDB:2HGS | ||||
| Method | X-ray diffraction | Resolution | 2.10 Å | Mutation | No | [2] |
| PDB Sequence |
TNWGSLLQDK
12 QQLEELARQA22 VDRALAEGVL32 LRTSQEPTSS42 EVVSYAPFTL52 FPSLVPSALL 62 EQAYAVQMDF72 NLLVDAVSQN82 AAFLEQTLSS92 TIKQDDFTAR102 LFDIHKQVLK 112 EGIAQTVFLG122 LNRSDYMFQR132 SADGSPALKQ142 IEINTISASF152 GGLASRTPAV 162 HRHVLSVLSK172 TKEAGKILSN182 NPSKGLALGI192 AKAWELYGSP202 NALVLLIAQE 212 KERNIFDQRA222 IENELLARNI232 HVIRRTFEDI242 SEKGSLDQDR252 RLFVDGQEIA 262 VVYFRDGYMP272 RQYSLQNWEA282 RLLLERSHAA292 KCPDIATQLA302 GTKKVQQELS 312 RPGMLEMLLP322 GQPEAVARLR332 ATFAGLYSLD342 VGEEGDQAIA352 EALAAPSRFV 362 LKPQREGGGN372 NLYGEEMVQA382 LKQLKDSEER392 ASYILMEKIE402 PEPFENCLLR 412 PGSPARVVQC422 ISELGIFGVY432 VRQEKTLVMN442 KHVGHLLRTK452 AIEHADGGVA 462 AGVAVLDNPY472 PV
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ARG125
2.991
ASN146
3.968
ILE148
3.268
SER149
2.744
ALA150
3.642
SER151
2.685
PHE152
3.451
GLU214
2.450
ASN216
3.084
ASP219
4.776
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| Ligand Name: adenosine diphosphate | Ligand Info | |||||
| Structure Description | HUMAN GLUTATHIONE SYNTHETASE | PDB:2HGS | ||||
| Method | X-ray diffraction | Resolution | 2.10 Å | Mutation | No | [2] |
| PDB Sequence |
TNWGSLLQDK
12 QQLEELARQA22 VDRALAEGVL32 LRTSQEPTSS42 EVVSYAPFTL52 FPSLVPSALL 62 EQAYAVQMDF72 NLLVDAVSQN82 AAFLEQTLSS92 TIKQDDFTAR102 LFDIHKQVLK 112 EGIAQTVFLG122 LNRSDYMFQR132 SADGSPALKQ142 IEINTISASF152 GGLASRTPAV 162 HRHVLSVLSK172 TKEAGKILSN182 NPSKGLALGI192 AKAWELYGSP202 NALVLLIAQE 212 KERNIFDQRA222 IENELLARNI232 HVIRRTFEDI242 SEKGSLDQDR252 RLFVDGQEIA 262 VVYFRDGYMP272 RQYSLQNWEA282 RLLLERSHAA292 KCPDIATQLA302 GTKKVQQELS 312 RPGMLEMLLP322 GQPEAVARLR332 ATFAGLYSLD342 VGEEGDQAIA352 EALAAPSRFV 362 LKPQREGGGN372 NLYGEEMVQA382 LKQLKDSEER392 ASYILMEKIE402 PEPFENCLLR 412 PGSPARVVQC422 ISELGIFGVY432 VRQEKTLVMN442 KHVGHLLRTK452 AIEHADGGVA 462 AGVAVLDNPY472 PV
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MET129
3.846
ILE143
3.492
GLU144
3.021
ASN146
4.034
LYS305
2.904
VAL362
3.834
LYS364
2.606
ARG367
3.983
GLU368
2.820
GLY369
3.304
GLY370
2.671
GLY371
4.685
ASN372
4.357
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| Click to View More Binding Site Information of This Target with Different Ligands | ||||||
| Different Human System Profiles of Target | Top |
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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
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There is no similarity protein (E value < 0.005) for this target
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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 |
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| Cysteine and methionine metabolism | hsa00270 | Affiliated Target |
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| Class: Metabolism => Amino acid metabolism | Pathway Hierarchy | ||
| Glutathione metabolism | hsa00480 | Affiliated Target |
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| Class: Metabolism => Metabolism of other amino acids | Pathway Hierarchy | ||
| Ferroptosis | hsa04216 | Affiliated Target |
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| Class: Cellular Processes => Cell growth and death | Pathway Hierarchy | ||
| Degree | 9 | Degree centrality | 9.67E-04 | Betweenness centrality | 6.21E-04 |
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| Closeness centrality | 1.69E-01 | Radiality | 1.26E+01 | Clustering coefficient | 2.22E-01 |
| Neighborhood connectivity | 4.78E+00 | Topological coefficient | 2.12E-01 | Eccentricity | 13 |
| Download | Click to Download the Full PPI Network of This Target | ||||
| References | Top | |||||
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| REF 1 | Nineteen-year follow-up of a patient with severe glutathione synthetase deficiency. J Hum Genet. 2016 Jul;61(7):669-72. | |||||
| REF 2 | Molecular basis of glutathione synthetase deficiency and a rare gene permutation event. EMBO J. 1999 Jun 15;18(12):3204-13. | |||||
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