Target Information
| Target General Information | Top | |||||
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| Target ID |
T98711
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| Target Name |
HUMAN cholinesterase (BCHE)
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| Synonyms |
Pseudocholinesterase; Choline esterase II; CHE1; Butyrylcholine esterase; Acylcholine acylhydrolase
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| Gene Name |
BCHE
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| Function |
Esterase with broad substrate specificity. Contributes to the inactivation of the neurotransmitter acetylcholine. Can degrade neurotoxic organophosphate esters.
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| BioChemical Class |
Type-B carboxylesterase/lipase
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| UniProt ID | ||||||
| EC Number |
EC 3.1.1.8
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| Sequence |
MHSKVTIICIRFLFWFLLLCMLIGKSHTEDDIIIATKNGKVRGMNLTVFGGTVTAFLGIP
YAQPPLGRLRFKKPQSLTKWSDIWNATKYANSCCQNIDQSFPGFHGSEMWNPNTDLSEDC LYLNVWIPAPKPKNATVLIWIYGGGFQTGTSSLHVYDGKFLARVERVIVVSMNYRVGALG FLALPGNPEAPGNMGLFDQQLALQWVQKNIAAFGGNPKSVTLFGESAGAASVSLHLLSPG SHSLFTRAILQSGSFNAPWAVTSLYEARNRTLNLAKLTGCSRENETEIIKCLRNKDPQEI LLNEAFVVPYGTPLSVNFGPTVDGDFLTDMPDILLELGQFKKTQILVGVNKDEGTAFLVY GAPGFSKDNNSIITRKEFQEGLKIFFPGVSEFGKESILFHYTDWVDDQRPENYREALGDV VGDYNFICPALEFTKKFSEWGNNAFFYYFEHRSSKLPWPEWMGVMHGYEIEFVFGLPLER RDNYTKAEEILSRSIVKRWANFAKYGNPNETQNNSTSWPVFKSTEQKYLTLNTESTRIMT KLRAQQCRFWTSFFPKVLEMTGNIDEAEWEWKAGFHRWNNYMMDWKNQFNDYTSKKESCV GL 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: Tacrine | Ligand Info | |||||
| Structure Description | Human butyrylcholinesterase in complex with tacrine | PDB:4BDS | ||||
| Method | X-ray diffraction | Resolution | 2.10 Å | Mutation | Yes | [2] |
| PDB Sequence |
IIIATKNGKV
13 RGMQLTVFGG23 TVTAFLGIPY33 AQPPLGRLRF43 KKPQSLTKWS53 DIWNATKYAN 63 SCCQNIDQSF73 PGFHGSEMWN83 PNTDLSEDCL93 YLNVWIPAPK103 PKNATVLIWI 113 YGGGFQTGTS123 SLHVYDGKFL133 ARVERVIVVS143 MNYRVGALGF153 LALPGNPEAP 163 GNMGLFDQQL173 ALQWVQKNIA183 AFGGNPKSVT193 LFGESAGAAS203 VSLHLLSPGS 213 HSLFTRAILQ223 SGSFNAPWAV233 TSLYEARNRT243 LNLAKLTGCS253 RENETEIIKC 263 LRNKDPQEIL273 LNEAFVVPYG283 TPLSVNFGPT293 VDGDFLTDMP303 DILLELGQFK 313 KTQILVGVNK323 DEGTAFLVYG333 APGFSKDNNS343 IITRKEFQEG353 LKIFFPGVSE 363 FGKESILFHY373 TDWVQRPENY385 REALGDVVGD395 YNFICPALEF405 TKKFSEWGNN 415 AFFYYFEHRS425 SKLPWPEWMG435 VMHGYEIEFV445 FGLPLERRDQ455 YTKAEEILSR 465 SIVKRWANFA475 KYGNPQETQN485 QSTSWPVFKS495 TEQKYLTLNT505 ESTRIMTKLR 515 AQQCRFWTSF525 FPKV
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| Ligand Name: Beta-L-fucose | Ligand Info | |||||
| Structure Description | Human Butyrylcholinesterase complexed with N-Propargyliperidines | PDB:5LKR | ||||
| Method | X-ray diffraction | Resolution | 2.52 Å | Mutation | No | [3] |
| PDB Sequence |
DIIIATKNGK
12 VRGMNLTVFG22 GTVTAFLGIP32 YAQPPLGRLR42 FKKPQSLTKW52 SDIWNATKYA 62 NSCCQNIDQS72 FPGFHGSEMW82 NPNTDLSEDC92 LYLNVWIPAP102 KPKNATVLIW 112 IYGGGFQTGT122 SSLHVYDGKF132 LARVERVIVV142 SMNYRVGALG152 FLALPGNPEA 162 PGNMGLFDQQ172 LALQWVQKNI182 AAFGGNPKSV192 TLFGESAGAA202 SVSLHLLSPG 212 SHSLFTRAIL222 QSGSFNAPWA232 VTSLYEARNR242 TLNLAKLTGC252 SRENETEIIK 262 CLRNKDPQEI272 LLNEAFVVPY282 GTPLSVNFGP292 TVDGDFLTDM302 PDILLELGQF 312 KKTQILVGVN322 KDEGTAFLVY332 GAPGFSKDNN342 SIITRKEFQE352 GLKIFFPGVS 362 EFGKESILFH372 YTDWVDDQRP382 ENYREALGDV392 VGDYNFICPA402 LEFTKKFSEW 412 GNNAFFYYFE422 HRSSKLPWPE432 WMGVMHGYEI442 EFVFGLPLER452 RDNYTKAEEI 462 LSRSIVKRWA472 NFAKYGNPNE482 TQNNSTSWPV492 FKSTEQKYLT502 LNTESTRIMT 512 KLRAQQCRFW522 TSFFPKVL
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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).
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
Biological Network Descriptors
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| Protein Name | Pfam ID | Percentage of Identity (%) | E value |
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| Arylacetamide deacetylase (AADAC) | 31.707 (39/123) | 3.72E-05 |
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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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| Degree | 1 | Degree centrality | 1.07E-04 | Betweenness centrality | 0.00E+00 |
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| Closeness centrality | 1.71E-01 | Radiality | 1.27E+01 | Clustering coefficient | 0.00E+00 |
| Neighborhood connectivity | 1.30E+01 | Topological coefficient | 1.00E+00 | 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 | Hematological Findings and Complications of COVID-19. Am J Hematol. 2020 Apr 13. doi: 10.1002/ajh.25829. | |||||
| REF 2 | Crystal structures of human cholinesterases in complex with huprine W and tacrine: elements of specificity for anti-Alzheimer's drugs targeting acetyl- and butyryl-cholinesterase. Biochem J. 2013 Aug 1;453(3):393-9. | |||||
| REF 3 | N-Propargylpiperidines with naphthalene-2-carboxamide or naphthalene-2-sulfonamide moieties: Potential multifunctional anti-Alzheimer's agents. Bioorg Med Chem. 2017 Jan 15;25(2):633-645. | |||||
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