Target Information
| Target General Information | Top | |||||
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| Target ID |
T67754
(Former ID: TTDR00094)
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| Target Name |
Transketolase (TK)
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| Synonyms |
TKT1; SDDHD; HEL107; HEL-S-48
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| Gene Name |
TKT
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| Target Type |
Literature-reported target
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[1] | ||||
| Function |
Catalyzes the transfer of a two-carbon ketol group from a ketose donor to an aldose acceptor, via a covalent intermediate with the cofactor thiamine pyrophosphate.
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| BioChemical Class |
Transketolase
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| UniProt ID | ||||||
| EC Number |
EC 2.2.1.1
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| Sequence |
MESYHKPDQQKLQALKDTANRLRISSIQATTAAGSGHPTSCCSAAEIMAVLFFHTMRYKS
QDPRNPHNDRFVLSKGHAAPILYAVWAEAGFLAEAELLNLRKISSDLDGHPVPKQAFTDV ATGSLGQGLGAACGMAYTGKYFDKASYRVYCLLGDGELSEGSVWEAMAFASIYKLDNLVA ILDINRLGQSDPAPLQHQMDIYQKRCEAFGWHAIIVDGHSVEELCKAFGQAKHQPTAIIA KTFKGRGITGVEDKESWHGKPLPKNMAEQIIQEIYSQIQSKKKILATPPQEDAPSVDIAN IRMPSLPSYKVGDKIATRKAYGQALAKLGHASDRIIALDGDTKNSTFSEIFKKEHPDRFI ECYIAEQNMVSIAVGCATRNRTVPFCSTFAAFFTRAFDQIRMAAISESNINLCGSHCGVS IGEDGPSQMALEDLAMFRSVPTSTVFYPSDGVATEKAVELAANTKGICFIRTSRPENAII YNNNEDFQVGQAKVVLKSKDDQVTVIGAGVTLHEALAAAELLKKEKINIRVLDPFTIKPL DRKLILDSARATKGRILTVEDHYYEGGIGEAVSSAVVGEPGITVTHLAVNRVPRSGKPAE LLKMFGIDRDAIAQAVRGLITKA Click to Show/Hide
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| 3D Structure | Click to Show 3D Structure of This Target | PDB | ||||
| ADReCS ID | BADD_A01462 ; BADD_A05947 | |||||
| HIT2.0 ID | T47YS7 | |||||
| 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: Thiamin diphosphate | Ligand Info | |||||
| Structure Description | Human transketolase in covalent complex with donor ketose D-xylulose-5-phosphate, crystal 1 | PDB:4KXV | ||||
| Method | X-ray diffraction | Resolution | 0.97 Å | Mutation | No | [2] |
| PDB Sequence |
ESYHKPDQQK
11 LQALKDTANR21 LRISSIQATT31 AAGSGHPTSC41 CSAAEIMAVL51 FFHTMRYKSQ 61 DPRNPHNDRF71 VLSKGHAAPI81 LYAVWAEAGF91 LAEAELLNLR101 KISSDLDGHP 111 VPKQAFTDVA121 TGSLGQGLGA131 ACGMAYTGKY141 FDKASYRVYC151 LLGDGELSEG 161 SVWEAMAFAS171 IYKLDNLVAI181 LDINRLGQSD191 PAPLQHQMDI201 YQKRCEAFGW 211 HAIIVDGHSV221 EELCKAFGQA231 KHQPTAIIAK241 TFKGRGITGV251 EDKESWHGKP 261 LPKNMAEQII271 QEIYSQIQSK281 KKILATPPQE291 DAPSVDIANI301 RMPSLPSYKV 311 GDKIATRKAY321 GQALAKLGHA331 SDRIIALDGD341 TKNSTFSEIF351 KKEHPDRFIE 361 CYIAEQNMVS371 IAVGCATRNR381 TVPFCSTFAA391 FFTRAFDQIR401 MAAISESNIN 411 LCGSHCGVSI421 GEDGPSQMAL431 EDLAMFRSVP441 TSTVFYPSDG451 VATEKAVELA 461 ANTKGICFIR471 TSRPENAIIY481 NNNEDFQVGQ491 AKVVLKSKDD501 QVTVIGAGVT 511 LHEALAAAEL521 LKKEKINIRV531 LDPFTIKPLD541 RKLILDSARA551 TKGRILTVED 561 HYYEGGIGEA571 VSSAVVGEPG581 ITVTHLAVNR591 VPRSGKPAEL601 LKMFGIDRDA 611 IAQAVRGLIT621
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| Click to View More Binding Site Information of This Target and Ligand Pair | ||||||
| Ligand Name: Xylitol 5-phosphate | Ligand Info | |||||
| Structure Description | Human transketolase in covalent complex with donor ketose D-xylulose-5-phosphate, crystal 1 | PDB:4KXV | ||||
| Method | X-ray diffraction | Resolution | 0.97 Å | Mutation | No | [2] |
| PDB Sequence |
ESYHKPDQQK
11 LQALKDTANR21 LRISSIQATT31 AAGSGHPTSC41 CSAAEIMAVL51 FFHTMRYKSQ 61 DPRNPHNDRF71 VLSKGHAAPI81 LYAVWAEAGF91 LAEAELLNLR101 KISSDLDGHP 111 VPKQAFTDVA121 TGSLGQGLGA131 ACGMAYTGKY141 FDKASYRVYC151 LLGDGELSEG 161 SVWEAMAFAS171 IYKLDNLVAI181 LDINRLGQSD191 PAPLQHQMDI201 YQKRCEAFGW 211 HAIIVDGHSV221 EELCKAFGQA231 KHQPTAIIAK241 TFKGRGITGV251 EDKESWHGKP 261 LPKNMAEQII271 QEIYSQIQSK281 KKILATPPQE291 DAPSVDIANI301 RMPSLPSYKV 311 GDKIATRKAY321 GQALAKLGHA331 SDRIIALDGD341 TKNSTFSEIF351 KKEHPDRFIE 361 CYIAEQNMVS371 IAVGCATRNR381 TVPFCSTFAA391 FFTRAFDQIR401 MAAISESNIN 411 LCGSHCGVSI421 GEDGPSQMAL431 EDLAMFRSVP441 TSTVFYPSDG451 VATEKAVELA 461 ANTKGICFIR471 TSRPENAIIY481 NNNEDFQVGQ491 AKVVLKSKDD501 QVTVIGAGVT 511 LHEALAAAEL521 LKKEKINIRV531 LDPFTIKPLD541 RKLILDSARA551 TKGRILTVED 561 HYYEGGIGEA571 VSSAVVGEPG581 ITVTHLAVNR591 VPRSGKPAEL601 LKMFGIDRDA 611 IAQAVRGLIT621
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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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| Pentose phosphate pathway | hsa00030 | Affiliated Target |
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| Class: Metabolism => Carbohydrate metabolism | Pathway Hierarchy | ||
| Degree | 18 | Degree centrality | 1.93E-03 | Betweenness centrality | 1.56E-03 |
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| Closeness centrality | 2.08E-01 | Radiality | 1.36E+01 | Clustering coefficient | 3.53E-01 |
| Neighborhood connectivity | 1.53E+01 | Topological coefficient | 1.59E-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 | ||||||
| Target Regulators | Top | |||||
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| Target-regulating microRNAs | ||||||
| Target-interacting Proteins | ||||||
| Target Affiliated Biological Pathways | Top | |||||
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| BioCyc | [+] 2 BioCyc Pathways | + | ||||
| 1 | Pentose phosphate pathway | |||||
| 2 | Pentose phosphate pathway (non-oxidative branch) | |||||
| KEGG Pathway | [+] 5 KEGG Pathways | + | ||||
| 1 | Pentose phosphate pathway | |||||
| 2 | Metabolic pathways | |||||
| 3 | Biosynthesis of antibiotics | |||||
| 4 | Carbon metabolism | |||||
| 5 | Biosynthesis of amino acids | |||||
| Panther Pathway | [+] 1 Panther Pathways | + | ||||
| 1 | Pentose phosphate pathway | |||||
| Pathwhiz Pathway | [+] 2 Pathwhiz Pathways | + | ||||
| 1 | Pentose Phosphate Pathway | |||||
| 2 | Warburg Effect | |||||
| WikiPathways | [+] 3 WikiPathways | + | ||||
| 1 | Metabolism of carbohydrates | |||||
| 2 | Integration of energy metabolism | |||||
| 3 | Pentose Phosphate Pathway | |||||
| References | Top | |||||
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| REF 1 | How many drug targets are there Nat Rev Drug Discov. 2006 Dec;5(12):993-6. | |||||
| REF 2 | Sub-?ngstr?m-resolution crystallography reveals physical distortions that enhance reactivity of a covalent enzymatic intermediate. Nat Chem. 2013 Sep;5(9):762-7. | |||||
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