Target Information
| Target General Information | Top | |||||
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| Target ID |
T77721
(Former ID: TTDR00623)
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| Target Name |
Glycerol-3-phosphate dehydrogenase (GPD1)
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| Synonyms |
Glycerol-3-phosphate dehydrogenase [NAD(+)], cytoplasmic; GPDH-C; GPD-C
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| Gene Name |
GPD1
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| Target Type |
Literature-reported target
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[1] | ||||
| Function |
Catalyzes the reversible redox conversion of dihydroxyacetone phosphate (a.k.a. glycerone phosphate, outdated) to sn-glycerol 3-phosphate. serves as a major link between carbohydrate metabolism and lipid metabolism. A major contributor of electrons to the electron transport chain in the mitochondria.
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| BioChemical Class |
Short-chain dehydrogenases reductase
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| UniProt ID | ||||||
| EC Number |
EC 1.1.1.8
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| Sequence |
MASKKVCIVGSGNWGSAIAKIVGGNAAQLAQFDPRVTMWVFEEDIGGKKLTEIINTQHEN
VKYLPGHKLPPNVVAVPDVVQAAEDADILIFVVPHQFIGKICDQLKGHLKANATGISLIK GVDEGPNGLKLISEVIGERLGIPMSVLMGANIASEVADEKFCETTIGCKDPAQGQLLKEL MQTPNFRITVVQEVDTVEICGALKNVVAVGAGFCDGLGFGDNTKAAVIRLGLMEMIAFAK LFCSGPVSSATFLESCGVADLITTCYGGRNRKVAEAFARTGKSIEQLEKELLNGQKLQGP ETARELYSILQHKGLVDKFPLFMAVYKVCYEGQPVGEFIHCLQNHPEHM Click to Show/Hide
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| 3D Structure | Click to Show 3D Structure of This Target | PDB | ||||
| HIT2.0 ID | T63C6D | |||||
| 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: Nicotinamide-Adenine-Dinucleotide | Ligand Info | |||||
| Structure Description | Binary Complex of Human Glycerol 3-Phosphate Dehydrogenase, R269A mutant | PDB:6PYP | ||||
| Method | X-ray diffraction | Resolution | 1.95 Å | Mutation | Yes | [2] |
| PDB Sequence |
ASKKVCIVGS
11 GNWGSAIAKI21 VGGNAAQLAQ31 FDPRVTMWVF41 EEDIGGKKLT51 EIINTQHENV 61 KYLPGHKLPP71 NVVAVPDVVQ81 AAEDADILIF91 VVPHQFIGKI101 CDQLKGHLKA 111 NATGISLIKG121 VDEGPNGLKL131 ISEVIGERLG141 IPMSVLMGAN151 IASEVADEKF 161 CETTIGCKDP171 AQGQLLKELM181 QTPNFRITVV191 QEVDTVEICG201 ALKNVVAVGA 211 GFCDGLGFGD221 NTKAAVIRLG231 LMEMIAFAKL241 FCSGPVSSAT251 FLESCGVADL 261 ITTCYGGANR271 KVAEAFARTG281 KSIEQLEKEL291 LNGQKLQGPE301 TARELYSILQ 311 HKGLVDKFPL321 FMAVYKVCYE331 GQPVGEFIHC341 LQNHPEHM
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GLY10
3.089
SER11
2.680
GLY12
2.538
ASN13
2.165
TRP14
2.260
GLY15
3.214
TRP39
3.000
VAL40
4.203
PHE41
2.442
GLU43
4.021
ASN60
4.604
TYR63
2.946
VAL92
3.266
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| Click to View More Binding Site Information of This Target and Ligand Pair | ||||||
| Ligand Name: Pentaerythritol | Ligand Info | |||||
| Structure Description | Unliganded Human Glycerol 3-Phosphate Dehydrogenase | PDB:6E8Y | ||||
| Method | X-ray diffraction | Resolution | 1.85 Å | Mutation | No | [3] |
| PDB Sequence |
ASKKVCIVGS
11 GNWGSAIAKI21 VGGNAAQLAQ31 FDPRVTMWVF41 EEDILTEIIN55 TQHENVKYLP 65 GHKLPPNVVA75 VPDVVQAAED85 ADILIFVVPH95 QFIGKICDQL105 KGHLKANATG 115 ISLIKGVDEG125 PNGLKLISEV135 IGERLGIPMS145 VLMGANIASE155 VADEKFCETT 165 IGCKDPAQGQ175 LLKELMQTPN185 FRITVVQEVD195 TVEICGALKN205 VVAVGAGFCD 215 GLGFGDNTKA225 AVIRLGLMEM235 IAFAKLFCSG245 PVSSATFLES255 CGVADLITTC 265 YGGRNRKVAE275 AFARTGKSIE285 QLEKELLNGQ295 KLQGPETARE305 LYSILQHKGL 315 VDKFPLFMAV325 YKVCYEGQPV335 GEFIHCLQNH345 PEHM
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| 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 |
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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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| Glycerophospholipid metabolism | hsa00564 | Affiliated Target |
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| Class: Metabolism => Lipid metabolism | Pathway Hierarchy | ||
| Degree | 3 | Degree centrality | 3.22E-04 | Betweenness centrality | 2.60E-04 |
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| Closeness centrality | 1.66E-01 | Radiality | 1.25E+01 | Clustering coefficient | 0.00E+00 |
| Neighborhood connectivity | 1.03E+01 | Topological coefficient | 3.33E-01 | Eccentricity | 12 |
| Download | Click to Download the Full PPI Network of This Target | ||||
| References | Top | |||||
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| REF 1 | A potential target enzyme for trypanocidal drugs revealed by the crystal structure of NAD-dependent glycerol-3-phosphate dehydrogenase from Leishma... Structure. 2000 May 15;8(5):541-52. | |||||
| REF 2 | Modeling the Role of a Flexible Loop and Active Site Side Chains in Hydride Transfer Catalyzed by Glycerol-3-phosphate Dehydrogenase. ACS Catal. 2020 Oct 2;10(19):11253-11267. | |||||
| REF 3 | Human Glycerol 3-Phosphate Dehydrogenase: X-ray Crystal Structures That Guide the Interpretation of Mutagenesis Studies. Biochemistry. 2019 Feb 26;58(8):1061-1073. | |||||
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