Structure of PDB 4wnu Chain A Binding Site BS02

Receptor Information

>4wnu Chain A (length=449) Species: 9606 (Homo sapiens)

GKLPPGPNTPYCFDQLRRRFGDVFSLQLAWTPVVVLNGLAAVREALVTHG
EDTADRPPVPITQILGFGPRSQGVFLARYGPAWREQRRFSVSTLRNLGLS
LEQWVTEEAACLCAAFANHSGRPFRPNGLLDKAVSNVIASLTCGRRFEYD
DPRFLRLLDLAQEGLKEESGFLREVLNAVPVLLHIPALAGKVLRFQKAFL
TQLDELLTEHRMTWDPAQPPRDLTEAFLAEMEKAKGNPESSFNDENLRIV
VADLFSAGMVTTSTTLAWGLLLMILHPDVQRRVQQEIDDVIGQVRRPEMG
DQAHMPYTTAVIHEVQRFGDIVPLGVTHMTSRDIEVQGFRIPKGTTLITN
LSSVLKDEAVWEKPFRFHPEHFLDAQGHFVKPEAFLPFSAGRRACLGEPL
ARMELFLFFTSLLQHFSFSVPTGQPRPSHHGVFAFLVSPSPYELCAVPR

Ligand information

• Ligand ID: QDN
• InChI: InChI=1S/C20H24N2O2/c1-3-13-12-22-9-7-14(13)10-19(22)20(23)16-6-8-21-18-5-4-15(24-2)11-17(16)18/h3-6,8,11,13-14,19-20,23H,1,7,9-10,12H2,2H3/t13-,14-,19+,20-/m0/s1
• InChIKey: LOUPRKONTZGTKE-LHHVKLHASA-N
• SMILES:
  OpenEye OEToolkits 1.9.2: COc1ccc2c(c1)c(ccn2)C(C3CC4CCN3CC4C=C)O
  OpenEye OEToolkits 1.9.2: COc1ccc2c(c1)c(ccn2)[C@@H]([C@H]3C[C@@H]4CC[N@]3C[C@@H]4C=C)O
  CACTVS 3.385: COc1ccc2nccc([C@H](O)[C@H]3C[C@@H]4CC[N@]3C[C@@H]4C=C)c2c1
  CACTVS 3.385: COc1ccc2nccc([CH](O)[CH]3C[CH]4CC[N]3C[CH]4C=C)c2c1
  ACDLabs 12.01: O(c4cc1c(nccc1C(O)C2N3CCC(C2)C(/C=C)C3)cc4)C
• Formula: C20 H24 N2 O2
• Name: Quinidine;
  (9S)-6'-methoxycinchonan-9-ol
• ChEMBL: CHEMBL1294
• DrugBank: DB00908
• ZINC: ZINC000003831405
• PDB chain: 4wnu Chain A Residue 602

Receptor-Ligand Complex Structure

Structure summary

• PDB: 4wnu Contributions of Ionic Interactions and Protein Dynamics to Cytochrome P450 2D6 (CYP2D6) Substrate and Inhibitor Binding.
• Resolution: 2.26 Å
• Binding residue (original residue number in PDB): F120 G212 L213 E216 Q244 F247 S304 F483
• Binding residue (residue number reindexed from 1): F75 G164 L165 E168 Q196 F199 S256 F435
• Annotation score: 1
• Binding affinity: BindingDB: IC50=10.0nM,Ki=30nM

Enzymatic activity

• Catalytic site (original residue number in PDB): T309 F436 C443
• Catalytic site (residue number reindexed from 1): T261 F388 C395
• Enzyme Commision number: 1.14.14.-

Gene Ontology

Molecular Function

• GO:0004497 monooxygenase activity
• GO:0005506 iron ion binding
• GO:0016491 oxidoreductase activity
• GO:0016705 oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen
• GO:0016712 oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen
• GO:0020037 heme binding
• GO:0046872 metal ion binding
• GO:0062187 anandamide 8,9 epoxidase activity
• GO:0062188 anandamide 11,12 epoxidase activity
• GO:0062189 anandamide 14,15 epoxidase activity

Biological Process

• GO:0006631 fatty acid metabolic process
• GO:0006805 xenobiotic metabolic process
• GO:0008202 steroid metabolic process
• GO:0008203 cholesterol metabolic process
• GO:0008210 estrogen metabolic process
• GO:0009804 coumarin metabolic process
• GO:0009820 alkaloid metabolic process
• GO:0009822 alkaloid catabolic process
• GO:0016098 monoterpenoid metabolic process
• GO:0019369 arachidonate metabolic process
• GO:0033076 isoquinoline alkaloid metabolic process
• GO:0042178 xenobiotic catabolic process
• GO:0042572 retinol metabolic process
• GO:0042759 long-chain fatty acid biosynthetic process
• GO:0051100 negative regulation of binding
• GO:0070989 oxidative demethylation
• GO:0090350 negative regulation of cellular organofluorine metabolic process

Cellular Component

• GO:0005737 cytoplasm
• GO:0005739 mitochondrion
• GO:0005783 endoplasmic reticulum
• GO:0005789 endoplasmic reticulum membrane
• GO:0016020 membrane
• GO:0043231 intracellular membrane-bounded organelle

External links

• PDB: RCSB:4wnu, PDBe:4wnu, PDBj:4wnu
• PDBsum: 4wnu
• PubMed: 25555909
• UniProt: P10635|CP2D6_HUMAN Cytochrome P450 2D6 (Gene Name=CYP2D6)