Structure of PDB 6i0b Chain A Binding Site BS02

Receptor Information

>6i0b Chain A (length=526) Species: 9606 (Homo sapiens)

IIIATKNGKVRGMQLTVFGGTVTAFLGIPYAQPPLGRLRFKKPQSLTKWS
DIWNATKYANSCCQNIDQSFPGFHGSEMWNPNTDLSEDCLYLNVWIPAPK
PKNATVLIWIYGGGFQTGTSSLHVYDGKFLARVERVIVVSMNYRVGALGF
LALPGNPEAPGNMGLFDQQLALQWVQKNIAAFGGNPKSVTLFGESAGAAS
VSLHLLSPGSHSLFTRAILQSGSFNAPWAVTSLYEARNRTLNLAKLTGCS
RENETEIIKCLRNKDPQEILLNEAFVVPYGTPLSVNFGPTVDGDFLTDMP
DILLELGQFKKTQILVGVNKDEGTAFLVYGAPGFSKDNNSIITRKEFQEG
LKIFFPGVSEFGKESILFHYTDWVDDQRPENYREALGDVVGDYNFICPAL
EFTKKFSEWGNNAFFYYFEHRSSKLPWPEWMGVMHGYEIEFVFGLPLERR
DQYTKAEEILSRSIVKRWANFAKYGNPQETQNQSTSWPVFKSTEQKYLTL
NTESTRIMTKLRAQQCRFWTSFFPKV

Ligand information

• Ligand ID: 9A5
• InChI: InChI=1S/C30H36ClN5O/c31-21-13-14-24-28(18-21)36-27-12-6-4-10-23(27)29(24)33-15-7-1-2-8-16-34-30(37)25(32)17-20-19-35-26-11-5-3-9-22(20)26/h3,5,9,11,13-14,18-19,25,35H,1-2,4,6-8,10,12,15-17,32H2,(H,33,36)(H,34,37)/t25-/m0/s1
• InChIKey: MSZVAOQNSCIOAB-VWLOTQADSA-N
• SMILES:
  OpenEye OEToolkits 2.0.6: c1ccc2c(c1)c(c[nH]2)C[C@@H](C(=O)NCCCCCCNc3c4ccc(cc4nc5c3CCCC5)Cl)N
  CACTVS 3.385: N[CH](Cc1c[nH]c2ccccc12)C(=O)NCCCCCCNc3c4CCCCc4nc5cc(Cl)ccc35
  CACTVS 3.385: N[C@@H](Cc1c[nH]c2ccccc12)C(=O)NCCCCCCNc3c4CCCCc4nc5cc(Cl)ccc35
  OpenEye OEToolkits 2.0.6: c1ccc2c(c1)c(c[nH]2)CC(C(=O)NCCCCCCNc3c4ccc(cc4nc5c3CCCC5)Cl)N
• Formula: C30 H36 Cl N5 O
• Name: (2~{S})-2-azanyl-~{N}-[6-[(6-chloranyl-1,2,3,4-tetrahydroacridin-9-yl)amino]hexyl]-3-(1~{H}-indol-3-yl)propanamide
• ChEMBL: CHEMBL4596071
• PDB chain: 6i0b Chain A Residue 613

Receptor-Ligand Complex Structure

Structure summary

• PDB: 6i0b Novel tacrine-tryptophan hybrids: Multi-target directed ligands as potential treatment for Alzheimer's disease.
• Resolution: 2.384 Å
• Binding residue (original residue number in PDB): W82 G116 G117 T120 E197 P285 S287 A328 F329 Y332 W430 H438 Y440
• Binding residue (residue number reindexed from 1): W79 G113 G114 T117 E194 P282 S284 A325 F326 Y329 W427 H435 Y437
• Annotation score: 1
• Binding affinity: MOAD: ic50=9.1nM

Enzymatic activity

• Catalytic site (original residue number in PDB): G116 G117 G149 S198 A199 Y237 V288 F290 E325 H438
• Catalytic site (residue number reindexed from 1): G113 G114 G146 S195 A196 Y234 V285 F287 E322 H435
• Enzyme Commision number: 3.1.1.8: cholinesterase.

Gene Ontology

Molecular Function

• GO:0001540 amyloid-beta binding
• GO:0003824 catalytic activity
• GO:0003990 acetylcholinesterase activity
• GO:0004104 cholinesterase activity
• GO:0005515 protein binding
• GO:0016788 hydrolase activity, acting on ester bonds
• GO:0019899 enzyme binding
• GO:0033265 choline binding
• GO:0042802 identical protein binding
• GO:0052689 carboxylic ester hydrolase activity

Biological Process

• GO:0006581 acetylcholine catabolic process
• GO:0006805 xenobiotic metabolic process
• GO:0007584 response to nutrient
• GO:0007612 learning
• GO:0008285 negative regulation of cell population proliferation
• GO:0009410 response to xenobiotic stimulus
• GO:0014016 neuroblast differentiation
• GO:0016486 peptide hormone processing
• GO:0019695 choline metabolic process
• GO:0043279 response to alkaloid
• GO:0050783 cocaine metabolic process
• GO:0050805 negative regulation of synaptic transmission
• GO:0051384 response to glucocorticoid
• GO:0051593 response to folic acid

Cellular Component

• GO:0005576 extracellular region
• GO:0005615 extracellular space
• GO:0005641 nuclear envelope lumen
• GO:0005783 endoplasmic reticulum
• GO:0005788 endoplasmic reticulum lumen
• GO:0005886 plasma membrane
• GO:0072562 blood microparticle

External links

• PDB: RCSB:6i0b, PDBe:6i0b, PDBj:6i0b
• PDBsum: 6i0b
• PubMed: 30851693
• UniProt: P06276|CHLE_HUMAN Cholinesterase (Gene Name=BCHE)