Target Information
Target General Information | Top | |||||
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Target ID |
T01269
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Target Name |
HUMAN alpha-galactosidase A (GLA)
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Synonyms |
Melibiase; Agalsidase; Alpha-D-galactoside galactohydrolase; Alpha-D-galactosidase A
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Gene Name |
GLA
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Function |
Human protein galactosidase alpha interacts with SARS-CoV-2 Nsp14 protein with high significance, which indicates GLA as a potential therapeutic target.
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BioChemical Class |
Glycosylase
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UniProt ID | ||||||
EC Number |
EC 3.2.1.22
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Sequence |
MQLRNPELHLGCALALRFLALVSWDIPGARALDNGLARTPTMGWLHWERFMCNLDCQEEP
DSCISEKLFMEMAELMVSEGWKDAGYEYLCIDDCWMAPQRDSEGRLQADPQRFPHGIRQL ANYVHSKGLKLGIYADVGNKTCAGFPGSFGYYDIDAQTFADWGVDLLKFDGCYCDSLENL ADGYKHMSLALNRTGRSIVYSCEWPLYMWPFQKPNYTEIRQYCNHWRNFADIDDSWKSIK SILDWTSFNQERIVDVAGPGGWNDPDMLVIGNFGLSWNQQVTQMALWAIMAAPLFMSNDL RHISPQAKALLQDKDVIAINQDPLGKQGYQLRQGDNFEVWERPLSGLAWAVAMINRQEIG GPRSYTIAVASLGKGVACNPACFITQLLPVKRKLGFYEWTSRLRSHINPTGTVLLQLENT MQMSLKDLL Click to Show/Hide
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3D Structure | Click to Show 3D Structure of This Target | PDB |
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: Levovist | Ligand Info | |||||
Structure Description | Pharmacological Chaperoning in Human alpha-Galactosidase | PDB:3S5Z | ||||
Method | X-ray diffraction | Resolution | 2.00 Å | Mutation | No | [2] |
PDB Sequence |
LDNGLARTPT
41 MGWLHWERFM51 CNLDCQEEPD61 SCISEKLFME71 MAELMVSEGW81 KDAGYEYLCI 91 DDCWMAPQRD101 SEGRLQADPQ111 RFPHGIRQLA121 NYVHSKGLKL131 GIYADVGNKT 141 CAGFPGSFGY151 YDIDAQTFAD161 WGVDLLKFDG171 CYCDSLENLA181 DGYKHMSLAL 191 NRTGRSIVYS201 CEWPLYMWPF211 QKPNYTEIRQ221 YCNHWRNFAD231 IDDSWKSIKS 241 ILDWTSFNQE251 RIVDVAGPGG261 WNDPDMLVIG271 NFGLSWNQQV281 TQMALWAIMA 291 APLFMSNDLR301 HISPQAKALL311 QDKDVIAINQ321 DPLGKQGYQL331 RQGDNFEVWE 341 RPLSGLAWAV351 AMINRQEIGG361 PRSYTIAVAS371 LGKGVACNPA381 CFITQLLPVK 391 RKLGFYEWTS401 RLRSHINPTG411 TVLLQLENTM421
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Click to View More Binding Site Information of This Target and Ligand Pair | ||||||
Ligand Name: Migalastat | Ligand Info | |||||
Structure Description | Pharmacological Chaperoning in Human alpha-Galactosidase | PDB:3S5Y | ||||
Method | X-ray diffraction | Resolution | 2.10 Å | Mutation | No | [2] |
PDB Sequence |
LDNGLARTPT
41 MGWLHWERFM51 CNLDCQEEPD61 SCISEKLFME71 MAELMVSEGW81 KDAGYEYLCI 91 DDCWMAPQRD101 SEGRLQADPQ111 RFPHGIRQLA121 NYVHSKGLKL131 GIYADVGNKT 141 CAGFPGSFGY151 YDIDAQTFAD161 WGVDLLKFDG171 CYCDSLENLA181 DGYKHMSLAL 191 NRTGRSIVYS201 CEWPLYMWPF211 QKPNYTEIRQ221 YCNHWRNFAD231 IDDSWKSIKS 241 ILDWTSFNQE251 RIVDVAGPGG261 WNDPDMLVIG271 NFGLSWNQQV281 TQMALWAIMA 291 APLFMSNDLR301 HISPQAKALL311 QDKDVIAINQ321 DPLGKQGYQL331 RQGDNFEVWE 341 RPLSGLAWAV351 AMINRQEIGG361 PRSYTIAVAS371 LGKGVACNPA381 CFITQLLPVK 391 RKLGFYEWTS401 RLRSHINPTG411 TVLLQLENTM421
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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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Galactose metabolism | hsa00052 | Affiliated Target |
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Class: Metabolism => Carbohydrate metabolism | Pathway Hierarchy | ||
Glycerolipid metabolism | hsa00561 | Affiliated Target |
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Class: Metabolism => Lipid metabolism | Pathway Hierarchy | ||
Sphingolipid metabolism | hsa00600 | Affiliated Target |
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Class: Metabolism => Lipid metabolism | Pathway Hierarchy | ||
Glycosphingolipid biosynthesis - globo and isoglobo series | hsa00603 | Affiliated Target |
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Class: Metabolism => Glycan biosynthesis and metabolism | Pathway Hierarchy | ||
Lysosome | hsa04142 | Affiliated Target |
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Class: Cellular Processes => Transport and catabolism | Pathway Hierarchy |
Degree | 8 | Degree centrality | 8.59E-04 | Betweenness centrality | 1.14E-03 |
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Closeness centrality | 1.38E-01 | Radiality | 1.15E+01 | Clustering coefficient | 1.07E-01 |
Neighborhood connectivity | 4.13E+00 | Topological coefficient | 2.06E-01 | Eccentricity | 13 |
Download | Click to Download the Full PPI Network of This Target | ||||
Chemical Structure based Activity Landscape of Target | Top |
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Target Poor or Non Binders | Top | |||||
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Target Poor or Non Binders |
References | Top | |||||
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REF 1 | A SARS-CoV-2 Protein Interaction Map Reveals Targets for Drug Repurposing. Nature. 2020 Apr 30. doi: 10.1038/s41586-020-2286-9. | |||||
REF 2 | The molecular basis of pharmacological chaperoning in human Alpha-galactosidase. Chem Biol. 2011 Dec 23;18(12):1521-6. |
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