Structure of PDB 5k5e Chain A Binding Site BS01

Receptor Information

>5k5e Chain A (length=527) Species: 9606 (Homo sapiens)

DIIIATKNGKVRGMNLTVFGGTVTAFLGIPYAQPPLGRLRFKKPQSLTKW
SDIWNATKYANSCCQNIDQSFPGFHGSEMWNPNTDLSEDCLYLNVWIPAP
KPKNATVLIWIYGGGFQTGTSSLHVYDGKFLARVERVIVVSMNYRVGALG
FLALPGNPEAPGNMGLFDQQLALQWVQKNIAAFGGNPKSVTLFGESAGAA
SVSLHLLSPGSHSLFTRAILQSGSFNAPWAVTSLYEARNRTLNLAKLTGC
SRENETEIIKCLRNKDPQEILLNEAFVVPYGTPLSVNFGPTVDGDFLTDM
PDILLELGQFKKTQILVGVNKDEGTAFLVYGAPGFSKDNNSIITRKEFQE
GLKIFFPGVSEFGKESILFHYTDWVDDQRPENYREALGDVVGDYNFICPA
LEFTKKFSEWGNNAFFYYFEHRSSKLPWPEWMGVMHGYEIEFVFGLPLER
RDNYTKAEEILSRSIVKRWANFAKYGNPNETQNNSTSWPVFKSTEQKYLT
LNTESTRIMTKLRAQQCRFWTSFFPKV

Ligand information

• Ligand ID: 6QS
• InChI: InChI=1S/C30H32N2O4/c1-3-32-24-11-5-4-9-21(24)22-16-19(13-14-25(22)32)28-27(30(34)36-17-20-8-7-15-35-20)18(2)31-23-10-6-12-26(33)29(23)28/h4-5,9,11,13-14,16,20,28,31H,3,6-8,10,12,15,17H2,1-2H3/t20-,28+/m1/s1
• InChIKey: SHBFRAVLHSPWTB-NGOKVRLYSA-N
• SMILES:
  OpenEye OEToolkits 2.0.5: CCn1c2ccccc2c3c1ccc(c3)C4C5=C(CCCC5=O)NC(=C4C(=O)OCC6CCCO6)C
  OpenEye OEToolkits 2.0.5: CCn1c2ccccc2c3c1ccc(c3)[C@@H]4C5=C(CCCC5=O)NC(=C4C(=O)OC[C@H]6CCCO6)C
  CACTVS 3.385: CCn1c2ccccc2c3cc(ccc13)[CH]4C(=C(C)NC5=C4C(=O)CCC5)C(=O)OC[CH]6CCCO6
  CACTVS 3.385: CCn1c2ccccc2c3cc(ccc13)[C@H]4C(=C(C)NC5=C4C(=O)CCC5)C(=O)OC[C@H]6CCCO6
• Formula: C30 H32 N2 O4
• Name: [(2~{R})-oxolan-2-yl]methyl 4-(9-ethylcarbazol-3-yl)-2-methyl-5-oxidanylidene-4,6,7,8-tetrahydro-1~{H}-quinoline-3-carboxylate
• ZINC: ZINC000005223684
• PDB chain: 5k5e Chain A Residue 609

Receptor-Ligand Complex Structure

Structure summary

• PDB: 5k5e Discovery and Structure-Activity Relationships of a Highly Selective Butyrylcholinesterase Inhibitor by Structure-Based Virtual Screening.
• Resolution: 2.8 Å
• Binding residue (original residue number in PDB): W82 G115 G116 G117 E197 P285 F329 Y332 H438
• Binding residue (residue number reindexed from 1): W80 G113 G114 G115 E195 P283 F327 Y330 H436
• Annotation score: 1
• Binding affinity: PDBbind-CN: -logKd/Ki=6.35,IC50=0.443uM
  BindingDB: IC50=443nM

Enzymatic activity

• Catalytic site (original residue number in PDB): G116 G117 G149 S198 A199 Y237 V288 F290 E325 H438
• Catalytic site (residue number reindexed from 1): G114 G115 G147 S196 A197 Y235 V286 F288 E323 H436
• Enzyme Commision number: 3.1.1.8: cholinesterase.

Gene Ontology

Molecular Function

• GO:0001540 amyloid-beta binding
• GO:0003824 catalytic activity
• GO:0003990 acetylcholinesterase activity
• GO:0004104 cholinesterase activity
• GO:0005515 protein binding
• GO:0016788 hydrolase activity, acting on ester bonds
• GO:0019899 enzyme binding
• GO:0033265 choline binding
• GO:0042802 identical protein binding
• GO:0052689 carboxylic ester hydrolase activity

Biological Process

• GO:0006581 acetylcholine catabolic process
• GO:0006805 xenobiotic metabolic process
• GO:0007584 response to nutrient
• GO:0007612 learning
• GO:0008285 negative regulation of cell population proliferation
• GO:0009410 response to xenobiotic stimulus
• GO:0014016 neuroblast differentiation
• GO:0016486 peptide hormone processing
• GO:0019695 choline metabolic process
• GO:0043279 response to alkaloid
• GO:0050783 cocaine metabolic process
• GO:0050805 negative regulation of synaptic transmission
• GO:0051384 response to glucocorticoid
• GO:0051593 response to folic acid

Cellular Component

• GO:0005576 extracellular region
• GO:0005615 extracellular space
• GO:0005641 nuclear envelope lumen
• GO:0005783 endoplasmic reticulum
• GO:0005788 endoplasmic reticulum lumen
• GO:0005886 plasma membrane
• GO:0072562 blood microparticle

External links

• PDB: RCSB:5k5e, PDBe:5k5e, PDBj:5k5e
• PDBsum: 5k5e
• PubMed: 27405689
• UniProt: P06276|CHLE_HUMAN Cholinesterase (Gene Name=BCHE)