Structure of PDB 4xry Chain A Binding Site BS02

Receptor Information
>4xry Chain A (length=464) Species: 9606 (Homo sapiens) [Search protein sequence] [Download receptor structure] [Download structure with residue number starting from 1] [View receptor structure]
GKLPPGPLPLPGLGNLLHVDTPYCFDQLRRRFGDVFSLQLAWTPVVVLNG
LAAVREALVTHGEDTADRPPVPITQILGFGPRSQGVFLARYGPAWREQRR
FSVSTLRNLGLGKKSLEQWVTEEAACLCAAFANHSGRPFRPNGLLDKAVS
NVIASLTCGRRFEYDDPRFLRLLDLAQEGLKEESGFLREVLNAVPVLLHI
PALAGKVLRFQKAFLTQLDELLTEHRMTWDPAQPPRDLTEAFLAEMEKAK
GNPESSFNDENLRIVVADLFSAGMVTTSTTLAWGLLLMILHPDVQRRVQQ
EIDDVIGQVRRPEMGDQAHMPYTTAVIHEVQRFGDIVPLGVTHMTSRDIE
VQGFRIPKGTTLITNLSSVLKDEAVWEKPFRFHPEHFLDAQGHFVKPEAF
LPFSAGRRACLGEPLARMELFLFFTSLLQHFSFSVPTGQPRPSHHGVFAF
LVSPSPYELCAVPR
Ligand information
Ligand IDSI5
InChIInChI=1S/C17H18F2N4OS/c1-23-7-10(6-21-23)15-4-11-8-25-16(20)22-17(11,9-24-15)13-3-2-12(18)5-14(13)19/h2-3,5-7,11,15H,4,8-9H2,1H3,(H2,20,22)/t11-,15+,17-/m0/s1
InChIKeyJYDYMWJEZLKIBS-CXMBCZLWSA-N
SMILES
SoftwareSMILES
OpenEye OEToolkits 1.9.2Cn1cc(cn1)[C@H]2C[C@H]3CSC(=N[C@]3(CO2)c4ccc(cc4F)F)N
CACTVS 3.385Cn1cc(cn1)[CH]2C[CH]3CSC(=N[C]3(CO2)c4ccc(F)cc4F)N
OpenEye OEToolkits 1.9.2Cn1cc(cn1)C2CC3CSC(=NC3(CO2)c4ccc(cc4F)F)N
ACDLabs 12.01Fc1ccc(c(F)c1)C42N=C(SCC4CC(OC2)c3cn(nc3)C)N
CACTVS 3.385Cn1cc(cn1)[C@H]2C[C@H]3CSC(=N[C@]3(CO2)c4ccc(F)cc4F)N
FormulaC17 H18 F2 N4 O S
Name(4aR,6R,8aS)-8a-(2,4-difluorophenyl)-6-(1-methyl-1H-pyrazol-4-yl)-4,4a,5,6,8,8a-hexahydropyrano[3,4-d][1,3]thiazin-2-amine
ChEMBLCHEMBL3422238
DrugBank
ZINCZINC000146161986
PDB chain4xry Chain A Residue 602 [Download ligand structure] [Download structure with residue number starting from 1] [View ligand structure]
Receptor-Ligand Complex Structure
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PDB4xry Utilizing Structures of CYP2D6 and BACE1 Complexes To Reduce Risk of Drug-Drug Interactions with a Novel Series of Centrally Efficacious BACE1 Inhibitors.
Resolution2.5 Å
Binding residue
(original residue number in PDB)		F120 E216 Q244 S304 A305 F483
Binding residue
(residue number reindexed from 1)		F87 E183 Q211 S271 A272 F450
Annotation score1
Binding affinityMOAD: ic50=13.9uM
BindingDB: IC50=13900nM
Enzymatic activity
Catalytic site (original residue number in PDB) T309 F436 C443
Catalytic site (residue number reindexed from 1) T276 F403 C410
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

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Molecular Function
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Biological Process
View graph for
Cellular Component
External links
PDB RCSB:4xry, PDBe:4xry, PDBj:4xry
PDBsum4xry
PubMed25781223
UniProtP10635|CP2D6_HUMAN Cytochrome P450 2D6 (Gene Name=CYP2D6)

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