Structure of PDB 4xry Chain B Binding Site BS02

Receptor Information

>4xry Chain B (length=455) Species: 9606 (Homo sapiens)

GKLPPGPLPGNLLHVTPYCFDQLRRRFGDVFSLQLAWTPVVVLNGLAAVR
EALVTHGEDTADRPPVPITQILGFGPRSQGVFLARYGPAWREQRRFSVST
LRNLKSLEQWVTEEAACLCAAFANHSGRPFRPNGLLDKAVSNVIASLTCG
RRFEYDDPRFLRLLDLAQEGLKEESGFLREVLNAVPVLLHIPALAGKVLR
FQKAFLTQLDELLTEHRMTWDPAQPPRDLTEAFLAEMEKAKGNPESSFND
ENLRIVVADLFSAGMVTTSTTLAWGLLLMILHPDVQRRVQQEIDDVIGQV
RRPEMGDQAHMPYTTAVIHEVQRFGDIVPLGVTHMTSRDIEVQGFRIPKG
TTLITNLSSVLKDEAVWEKPFRFHPEHFLDAQGHFVKPEAFLPFSAGRRA
CLGEPLARMELFLFFTSLLQHFSFSVPTGQPRPSHHGVFAFLVSPSPYEL
CAVPR

Ligand information

• Ligand ID: HEM
• InChI: InChI=1S/C34H34N4O4.Fe/c1-7-21-17(3)25-13-26-19(5)23(9-11-33(39)40)31(37-26)16-32-24(10-12-34(41)42)20(6)28(38-32)15-30-22(8-2)18(4)27(36-30)14-29(21)35-25;/h7-8,13-16H,1-2,9-12H2,3-6H3,(H4,35,36,37,38,39,40,41,42);/q;+2/p-2/b25-13-,26-13-,27-14-,28-15-,29-14-,30-15-,31-16-,32-16-;
• InChIKey: KABFMIBPWCXCRK-RGGAHWMASA-L
• SMILES:
  OpenEye OEToolkits 1.7.6: Cc1c2n3c(c1CCC(=O)O)C=C4C(=C(C5=[N]4[Fe]36[N]7=C(C=C8N6C(=C5)C(=C8C)C=C)C(=C(C7=C2)C)C=C)C)CCC(=O)O
  CACTVS 3.385: CC1=C(CCC(O)=O)C2=Cc3n4[Fe]5|6|N2=C1C=c7n5c(=CC8=N|6C(=Cc4c(C)c3CCC(O)=O)C(=C8C=C)C)c(C)c7C=C
  ACDLabs 12.01: C=1c3c(c(c4C=C5C(=C(C=6C=C7C(=C(C8=CC=2C(=C(C=1N=2[Fe](n34)(N5=6)N78)CCC(=O)O)C)\C=C)C)\C=C)C)C)CCC(=O)O
• Formula: C34 H32 Fe N4 O4
• Name: PROTOPORPHYRIN IX CONTAINING FE;
  HEME
• DrugBank: DB18267
• PDB chain: 4xry Chain B Residue 601

Receptor-Ligand Complex Structure

Structure summary

• PDB: 4xry Utilizing Structures of CYP2D6 and BACE1 Complexes To Reduce Risk of Drug-Drug Interactions with a Novel Series of Centrally Efficacious BACE1 Inhibitors.
• Resolution: 2.5 Å
• Binding residue (original residue number in PDB): R101 F120 W128 R132 G306 T309 H376 P435 F436 S437 R441 C443 L444 G445
• Binding residue (residue number reindexed from 1): R63 F82 W90 R94 G264 T267 H334 P393 F394 S395 R399 C401 L402 G403
• Annotation score: 1

Enzymatic activity

• Catalytic site (original residue number in PDB): T309 F436 C443
• Catalytic site (residue number reindexed from 1): T267 F394 C401
• 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:4xry, PDBe:4xry, PDBj:4xry
• PDBsum: 4xry
• PubMed: 25781223
• UniProt: P10635|CP2D6_HUMAN Cytochrome P450 2D6 (Gene Name=CYP2D6)