Structure of PDB 6o4w Chain A Binding Site BS01

Receptor Information

>6o4w Chain A (length=540) Species: 9606 (Homo sapiens)

EDAELLVTVRGGRLRGIRLKTPGGPVSAFLGIPFAEPPMGPRRFLPPEPK
QPWSGVVDATTFQSVCYQYVDTLYPGFEGTEMWNPNRELSEDCLYLNVWT
PYPRPTSPTPVLVWIYGGGFYSGASSLDVYDGRFLVQAERTVLVSMNYRV
GAFGFLALPGSREAPGNVGLLDQRLALQWVQENVAAFGGDPTSVTLFGES
AGAASVGMHLLSPPSRGLFHRAVLQSGAPNGPWATVGMGEARRRATQLAH
LVGCPPGGTGGNDTELVACLRTRPAQVLVNHEWHVLPQESVFRFSFVPVV
DGDFLSDTPEALINAGDFHGLQVLVGVVKDEGSYFLVYGAPGFSKDNESL
ISRAEFLAGVRVGVPQVSDLAAEAVVLHYTDWLHPEDPARLREALSDVVG
DHNVVCPVAQLAGRLAAQGARVYAYVFEHRASTLSWPLWMGVPHGYEIEF
IFGIPLDPSRNYTAEEKIFAQRLMRYWANFARTGDPNEPRDPKAPQWPPY
TAGAQQYVSLDLRPLEVRRGLRAQACAFWNRFLPKLLSAT

Ligand information

• Ligand ID: E20
• InChI: InChI=1S/C24H29NO3/c1-27-22-14-19-13-20(24(26)21(19)15-23(22)28-2)12-17-8-10-25(11-9-17)16-18-6-4-3-5-7-18/h3-7,14-15,17,20H,8-13,16H2,1-2H3/t20-/m1/s1
• InChIKey: ADEBPBSSDYVVLD-HXUWFJFHSA-N
• SMILES:
  OpenEye OEToolkits 1.5.0: COc1cc2c(cc1OC)C(=O)C(C2)CC3CCN(CC3)Cc4ccccc4
  OpenEye OEToolkits 1.5.0: COc1cc2c(cc1OC)C(=O)[C@@H](C2)CC3CCN(CC3)Cc4ccccc4
  ACDLabs 10.04: O=C2c1cc(OC)c(OC)cc1CC2CC4CCN(Cc3ccccc3)CC4
  CACTVS 3.341: COc1cc2C[CH](CC3CCN(CC3)Cc4ccccc4)C(=O)c2cc1OC
  CACTVS 3.341: COc1cc2C[C@@H](CC3CCN(CC3)Cc4ccccc4)C(=O)c2cc1OC
• Formula: C24 H29 N O3
• Name: 1-BENZYL-4-[(5,6-DIMETHOXY-1-INDANON-2-YL)METHYL]PIPERIDINE;
  E2020
• ChEMBL: CHEMBL107316
• DrugBank: DB07701
• ZINC: ZINC000000897251
• PDB chain: 6o4w Chain A Residue 604

Receptor-Ligand Complex Structure

Structure summary

• PDB: 6o4w A new crystal form of human acetylcholinesterase for exploratory room-temperature crystallography studies.
• Resolution: 2.35 Å
• Binding residue (original residue number in PDB): Y72 W86 Y124 E202 W286 F295 Y337 F338 Y341
• Binding residue (residue number reindexed from 1): Y69 W83 Y121 E199 W283 F292 Y334 F335 Y338
• Annotation score: 1
• Binding affinity: PDBbind-CN: -logKd/Ki=8.47,Ki=3.4nM
  BindingDB: IC50=10.0nM,Ki=20.5nM,EC50=43nM

Enzymatic activity

• Catalytic site (original residue number in PDB): G121 G122 S203 A204 E334 H447
• Catalytic site (residue number reindexed from 1): G118 G119 S200 A201 E331 H444
• Enzyme Commision number: 3.1.1.7: acetylcholinesterase.

Gene Ontology

Molecular Function

• GO:0001540 amyloid-beta binding
• GO:0003990 acetylcholinesterase activity
• GO:0004104 cholinesterase activity
• GO:0005515 protein binding
• GO:0005518 collagen binding
• GO:0016787 hydrolase activity
• GO:0017171 serine hydrolase activity
• GO:0042166 acetylcholine binding
• GO:0042802 identical protein binding
• GO:0042803 protein homodimerization activity
• GO:0043236 laminin binding
• GO:0052689 carboxylic ester hydrolase activity

Biological Process

• GO:0001507 acetylcholine catabolic process in synaptic cleft
• GO:0001919 regulation of receptor recycling
• GO:0002076 osteoblast development
• GO:0006581 acetylcholine catabolic process
• GO:0007155 cell adhesion
• GO:0007399 nervous system development
• GO:0007416 synapse assembly
• GO:0031623 receptor internalization
• GO:0032223 negative regulation of synaptic transmission, cholinergic
• GO:0042982 amyloid precursor protein metabolic process
• GO:0050714 positive regulation of protein secretion
• GO:0060041 retina development in camera-type eye
• GO:0095500 acetylcholine receptor signaling pathway
• GO:0120162 positive regulation of cold-induced thermogenesis

Cellular Component

• GO:0005576 extracellular region
• GO:0005604 basement membrane
• GO:0005615 extracellular space
• GO:0005634 nucleus
• GO:0005794 Golgi apparatus
• GO:0005886 plasma membrane
• GO:0009986 cell surface
• GO:0016020 membrane
• GO:0031594 neuromuscular junction
• GO:0043083 synaptic cleft
• GO:0045202 synapse
• GO:0048471 perinuclear region of cytoplasm
• GO:0098552 side of membrane

External links

• PDB: RCSB:6o4w, PDBe:6o4w, PDBj:6o4w
• PDBsum: 6o4w
• PubMed: 31176713
• UniProt: P22303|ACES_HUMAN Acetylcholinesterase (Gene Name=ACHE)