Structure of PDB 4a16 Chain A Binding Site BS01

Receptor Information

>4a16 Chain A (length=540) Species: 10090 (Mus musculus)

EDPQLLVRVRGGQLRGIRLKAPGGPVSAFLGIPFAEPPVGSRRFMPPEPK
RPWSGVLDATTFQNVCYQYVDTLYPGFEGTEMWNPNRELSEDCLYLNVWT
PYPRPASPTPVLIWIYGGGFYSGAASLDVYDGRFLAQVEGAVLVSMNYRV
GTFGFLALPGSREAPGNVGLLDQRLALQWVQENIAAFGGDPMSVTLFGES
AGAASVGMHILSLPSRSLFHRAVLQSGTPNGPWATVSAGEARRRATLLAR
LVGCPPGGAGGNDTELIACLRTRPAQDLVDHEWHVLPQESIFRFSFVPVV
DGDFLSDTPEALINTGDFQDLQVLVGVVKDEGSYFLVYGVPGFSKDNESL
ISRAQFLAGVRIGVPQASDLAAEAVVLHYTDWLHPEDPTHLRDAMSAVVG
DHNVVCPVAQLAGRLAAQGARVYAYIFEHRASTLTWPLWMGVPHGYEIEF
IFGLPLDPSLNYTTEERIFAQRLMKYWTNFARTGDPNDPRDSKSPQWPPY
TTAAQQYVSLNLKPLEVRRGLRAQTCAFWNRFLPKLLSAT

Ligand information

• Ligand ID: H34
• InChI: InChI=1S/C23H26ClN5O/c24-17-4-5-19-20(11-17)26-21-10-15-7-14(8-16(9-15)22(21)23(19)25)3-1-2-6-29-12-18(13-30)27-28-29/h4-5,7,11-12,15-16,30H,1-3,6,8-10,13H2,(H2,25,26)/t15-,16+/m0/s1
• InChIKey: MHMXFYDLGYPRNA-JKSUJKDBSA-N
• SMILES:
  CACTVS 3.385: Nc1c2ccc(Cl)cc2nc3C[C@@H]4C[C@@H](CC(=C4)CCCCn5cc(CO)nn5)c13
  ACDLabs 12.01: Clc2ccc1c(N)c4c(nc1c2)CC5C=C(CCCCn3nnc(c3)CO)CC4C5
  CACTVS 3.385: Nc1c2ccc(Cl)cc2nc3C[CH]4C[CH](CC(=C4)CCCCn5cc(CO)nn5)c13
  OpenEye OEToolkits 1.9.2: c1cc2c(cc1Cl)nc3c(c2N)[C@H]4C[C@@H](C3)C=C(C4)CCCCn5cc(nn5)CO
  OpenEye OEToolkits 1.9.2: c1cc2c(cc1Cl)nc3c(c2N)C4CC(C3)C=C(C4)CCCCn5cc(nn5)CO
• Formula: C23 H26 Cl N5 O
• Name: (1-{4-[(7S,11S)-12-AMINO-3-CHLORO-6,7,10,11-TETRAHYDRO-7,11-METHANOCYCLOOCTA[B]QUINOLIN-9-YL]BUTYL}-1H-1,2,3-TRIAZOL-4-YL)METHANOL
• ZINC: ZINC000095920795
• PDB chain: 4a16 Chain A Residue 1545

Receptor-Ligand Complex Structure

Structure summary

• PDB: 4a16 Huprine Derivatives as Sub-Nanomolar Human Acetylcholinesterase Inhibitors: From Rational Design to Validation by X-Ray Crystallography.
• Resolution: 2.65 Å
• Binding residue (original residue number in PDB): W86 G121 Y124 E202 W286 F295 F297 Y337 F338 Y341 W439 H447 Y449
• Binding residue (residue number reindexed from 1): W83 G118 Y121 E199 W283 F292 F294 Y334 F335 Y338 W436 H444 Y446
• Annotation score: 1
• Binding affinity: PDBbind-CN: -logKd/Ki=9.37,IC50=0.43nM

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 F294 F296 E331 H444
• Enzyme Commision number: 3.1.1.7: acetylcholinesterase.

Gene Ontology

Molecular Function

• 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:0001919 regulation of receptor recycling
• GO:0002076 osteoblast development
• GO:0006581 acetylcholine catabolic process
• GO:0007155 cell adhesion
• GO:0031623 receptor internalization
• 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:0005794 Golgi apparatus
• GO:0005886 plasma membrane
• GO:0009986 cell surface
• GO:0016020 membrane
• GO:0031594 neuromuscular junction
• GO:0045202 synapse
• GO:0048471 perinuclear region of cytoplasm
• GO:0098552 side of membrane

External links

• PDB: RCSB:4a16, PDBe:4a16, PDBj:4a16
• PDBsum: 4a16
• PubMed: 22052791
• UniProt: P21836|ACES_MOUSE Acetylcholinesterase (Gene Name=Ache)