Structure of PDB 6ntg Chain A Binding Site BS01

Receptor Information

>6ntg Chain A (length=530) Species: 9606 (Homo sapiens)

EDAELLVTVRGGRLRGIRLKTPGGPVSAFLGIPFAEPPMGPRRFLPPEPK
QPWSGVVDATTFQSVCYQYVDTLYPGFEGTEMWNPNRELSEDCLYLNVWT
PYPRPTSPTPVLVWIYGGGFYSGASSLDVYDGRFLVQAERTVLVSMNYRV
GAFGFLALPGSREAPGNVGLLDQRLALQWVQENVAAFGGDPTSVTLFGES
AGAASVGMHLLSPPSRGLFHRAVLQSGAPNGPWATVGMGEARRRATQLAH
LVGCPGNDTELVACLRTRPAQVLVNHEWHVLPQESVFRFSFVPVVDGDFL
SDTPEALINAGDFHGLQVLVGVVKDEGSYFLVYGAPGFSKDNESLISRAE
FLAGVRVGVPQVSDLAAEAVVLHYTDWLHPEDPARLREALSDVVGDHNVV
CPVAQLAGRLAAQGARVYAYVFEHRASTLSWPLWMGVPHGYEIEFIFGIP
LDPSRNYTAEEKIFAQRLMRYWANFARTGDPNEPAPQWPPYTAGAQQYVS
LDLRPLEVRRGLRAQACAFWNRFLPKLLSA

Ligand information

• Ligand ID: HI6
• InChI: InChI=1S/C14H14N4O3/c15-14(19)12-4-7-17(8-5-12)10-21-11-18-6-2-1-3-13(18)9-16-20/h1-9H,10-11H2,(H-,15,19)/p+2
• InChIKey: FJZDLOMCEPUCII-UHFFFAOYSA-P
• SMILES:
  OpenEye OEToolkits 1.5.0: c1cc[n+](c(c1)\C=N\O)COC[n+]2ccc(cc2)C(=O)N
  CACTVS 3.341: NC(=O)c1cc[n+](COC[n+]2ccccc2C=NO)cc1
  CACTVS 3.341: NC(=O)c1cc[n+](COC[n+]2ccccc2\C=N\O)cc1
  OpenEye OEToolkits 1.5.0: c1cc[n+](c(c1)C=NO)COC[n+]2ccc(cc2)C(=O)N
  ACDLabs 10.04: O=C(N)c1cc[n+](cc1)COC[n+]2ccccc2\C=N\O
• Formula: C14 H16 N4 O3
• Name: 4-(AMINOCARBONYL)-1-[({2-[(E)-(HYDROXYIMINO)METHYL]PYRIDINIUM-1-YL}METHOXY)METHYL]PYRIDINIUM;
  1-(2-HYDROXY-IMINOMETHYLPYRIDINIUM)-1-(4-CARBOXYAMINO)-PYRIDINIUM DIMETHYLETHER
• ChEMBL: CHEMBL385181
• ZINC: ZINC000000005077
• PDB chain: 6ntg Chain A Residue 601

Receptor-Ligand Complex Structure

Structure summary

• PDB: 6ntg Insights into inhibition of human acetylcholinesterase by Novichok, A-series Nerve Agents
• Resolution: 2.652 Å
• Binding residue (original residue number in PDB): Y72 Y124 W286 F297 S298 Y341
• Binding residue (residue number reindexed from 1): Y69 Y121 W278 F289 S290 Y333
• Annotation score: 1
• Binding affinity: BindingDB: IC50=667800nM,Kd=93000nM

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 F289 F291 E326 H439
• 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:6ntg, PDBe:6ntg, PDBj:6ntg
• PDBsum: 6ntg
• UniProt: P22303|ACES_HUMAN Acetylcholinesterase (Gene Name=ACHE)