Structure of PDB 4bdt Chain A Binding Site BS01

Receptor Information

>4bdt Chain A (length=563) Species: 9606 (Homo sapiens)

DAELLVTVRGGRLRGIRLKTPGGPVSAFLGIPFAEPPMGPRRFLPPEPKQ
PWSGVVDATTFQSVCYQYVDTLYPGFEGTEMWNPNRELSEDCLYLNVWTP
YPRPTSPTPVLVWIYGGGFYSGASSLDVYDGRFLVQAERTVLVSMNYRVG
AFGFLALPGSREAPGNVGLLDQRLALQWVQENVAAFGGDPTSVTLFGESA
GAASVGMHLLSPPSRGLFHRAVLQSGAPNGPWATVGMGEARRRATQLAHL
VGCPPGGTGGNDTELVACLRTRPAQVLVNHEWHVLPQESVFRFSFVPVVD
GDFLSDTPEALINAGDFHGLQVLVGVVKDEGSYFLVYGAPGFSKDNESLI
SRAEFLAGVRVGVPQVSDLAAEAVVLHYTDWLHPEDPARLREALSDVVGD
HNVVCPVAQLAGRLAAQGARVYAYVFEHRASTLSWPLWMGVPHGYEIEFI
FGIPLDPSRNYTAEEKIFAQRLMRYWANFARTGDPNEPRDPKAPQWPPYT
AGAQQYVSLDLRPLEVRRGLRAQACAFWNRFLPKLLSATDTLDEAERQWK
AEFHRWSSYMVHW

Ligand information

• Ligand ID: HUW
• InChI: InChI=1S/C18H19ClN2O/c19-13-1-2-14-15(9-13)21-16-8-11-5-10(3-4-22)6-12(7-11)17(16)18(14)20/h1-2,5,9,11-12,22H,3-4,6-8H2,(H2,20,21)/t11-,12+/m0/s1
• InChIKey: GAOPELPOAHCRBF-NWDGAFQWSA-N
• SMILES:
  CACTVS 3.385: Nc1c2ccc(Cl)cc2nc3C[C@@H]4C[C@@H](CC(=C4)CCO)c13
  OpenEye OEToolkits 1.9.2: c1cc2c(cc1Cl)nc3c(c2N)C4CC(C3)C=C(C4)CCO
  OpenEye OEToolkits 1.9.2: c1cc2c(cc1Cl)nc3c(c2N)[C@H]4C[C@@H](C3)C=C(C4)CCO
  CACTVS 3.385: Nc1c2ccc(Cl)cc2nc3C[CH]4C[CH](CC(=C4)CCO)c13
  ACDLabs 12.01: Clc2ccc1c(N)c3c(nc1c2)CC4C=C(CC3C4)CCO
• Formula: C18 H19 Cl N2 O
• Name: HUPRINE W
• ZINC: ZINC000095920794
• PDB chain: 4bdt Chain A Residue 701

Receptor-Ligand Complex Structure

Structure summary

• PDB: 4bdt 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.
• Resolution: 3.104 Å
• Binding residue (original residue number in PDB): W86 G121 G122 S203 Y337 W439 H447
• Binding residue (residue number reindexed from 1): W82 G117 G118 S199 Y333 W435 H443
• Annotation score: 1
• Binding affinity: PDBbind-CN: -logKd/Ki=8.96,IC50=1.1nM

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): G117 G118 G150 S199 A200 G238 F293 F295 E330 H443
• 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:4bdt, PDBe:4bdt, PDBj:4bdt
• PDBsum: 4bdt
• PubMed: 23679855
• UniProt: P22303|ACES_HUMAN Acetylcholinesterase (Gene Name=ACHE)