Structure of PDB 4ey6 Chain A Binding Site BS01

Receptor Information

>4ey6 Chain A (length=530) Species: 9606 (Homo sapiens)

EDAELLVTVRGGRLRGIRLKTPGGPVSAFLGIPFAEPPMGPRRFLPPEPK
QPWSGVVDATTFQSVCYQYVDTLYPGFEGTEMWNPNRELSEDCLYLNVWT
PYPRPTSPTPVLVWIYGGGFYSGASSLDVYDGRFLVQAERTVLVSMNYRV
GAFGFLALPGSREAPGNVGLLDQRLALQWVQENVAAFGGDPTSVTLFGES
AGAASVGMHLLSPPSRGLFHRAVLQSGAPNGPWATVGMGEARRRATQLAH
LVGCPNDTELVACLRTRPAQVLVNHEWHVLPQESVFRFSFVPVVDGDFLS
DTPEALINAGDFHGLQVLVGVVKDEGSYFLVYGAPGFSKDNESLISRAEF
LAGVRVGVPQVSDLAAEAVVLHYTDWLHPEDPARLREALSDVVGDHNVVC
PVAQLAGRLAAQGARVYAYVFEHRASTLSWPLWMGVPHGYEIEFIFGIPL
DPSRNYTAEEKIFAQRLMRYWANFARTGDPNEPRDPQWPPYTAGAQQYVS
LDLRPLEVRRGLRAQACAFWNRFLPKLLSA

Ligand information

• Ligand ID: GNT
• InChI: InChI=1S/C17H21NO3/c1-18-8-7-17-6-5-12(19)9-14(17)21-16-13(20-2)4-3-11(10-18)15(16)17/h3-6,12,14,19H,7-10H2,1-2H3/t12-,14-,17-/m0/s1
• InChIKey: ASUTZQLVASHGKV-JDFRZJQESA-N
• SMILES:
  CACTVS 3.341: COc1ccc2CN(C)CC[C]34C=C[CH](O)C[CH]3Oc1c24
  OpenEye OEToolkits 1.5.0: C[N@@]1CC[C@@]23C=C[C@@H](C[C@@H]2Oc4c3c(ccc4OC)C1)O
  OpenEye OEToolkits 1.5.0: CN1CCC23C=CC(CC2Oc4c3c(ccc4OC)C1)O
  CACTVS 3.341: COc1ccc2CN(C)CC[C@@]34C=C[C@H](O)C[C@@H]3Oc1c24
  ACDLabs 10.04: OC2C=CC41c3c(ccc(OC)c3OC1C2)CN(CC4)C
• Formula: C17 H21 N O3
• Name: (-)-GALANTHAMINE
• ChEMBL: CHEMBL659
• DrugBank: DB00674
• ZINC: ZINC000000491073
• PDB chain: 4ey6 Chain A Residue 604

Receptor-Ligand Complex Structure

Structure summary

• PDB: 4ey6 Structures of human acetylcholinesterase in complex with pharmacologically important ligands.
• Resolution: 2.3983 Å
• Binding residue (original residue number in PDB): W86 G120 G121 G122 Y124 E202 S203 F295 F297 Y337 F338 H447
• Binding residue (residue number reindexed from 1): W83 G117 G118 G119 Y121 E199 S200 F286 F288 Y328 F329 H438
• Annotation score: 1
• Binding affinity: BindingDB: IC50=800nM,Ki=62nM,EC50=1100nM

Enzymatic activity

• Catalytic site (original residue number in PDB): G121 G122 G154 S203 A204 G242 F297 F299 E334 H447
• Catalytic site (residue number reindexed from 1): G118 G119 G151 S200 A201 G239 F288 F290 E325 H438
• 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:4ey6, PDBe:4ey6, PDBj:4ey6
• PDBsum: 4ey6
• PubMed: 23035744
• UniProt: P22303|ACES_HUMAN Acetylcholinesterase (Gene Name=ACHE)