Structure of PDB 5tfu Chain D Binding Site BS03

Receptor Information

>5tfu Chain D (length=453) Species: 9606 (Homo sapiens)

LPPGPLPQNTPYCFDQLRRRFGDVFSLQLAWTPVVVLNGLAAVREALVTH
GEDTADRPPVPITQILGFGPRSQGVFLARYGPAWREQRRFSVSTLRNLGL
GKKSLEQWVTEEAACLCAAFANHSGRPFRPNGLLDKAVSNVIASLTCGRR
FEYDDPRFLRLLDLAQEGLKEESGFLREVLNAVPVLLHIPALAGKVLRFQ
KAFLTQLDELLTEHRMTWDPAQPPRDLTEAFLAEMEKAKGNPESSFNDEN
LRIVVADLFSAGMVTTSTTLAWGLLLMILHPDVQRRVQQEIDDVIGQVRR
PEMGDQAHMPYTTAVIHEVQRFGDIVPLGVTHMTSRDIEVQGFRIPKGTT
LITNLSSVLKDEAVWEKPFRFHPEHFLDAQGHFVKPEAFLPFSAGRRACL
GEPLARMELFLFFTSLLQHFSFSVPTGQPRPSHHGVFAFLVSPSPYELCA
VPR

Ligand information

• Ligand ID: P6M
• InChI: InChI=1S/C17H20F5N3S/c1-9-7-15(2,25-14(23)26-9)11-5-10(12(18)6-13(11)19)8-24-16(3-4-16)17(20,21)22/h5-6,9,24H,3-4,7-8H2,1-2H3,(H2,23,25)/t9-,15+/m1/s1
• InChIKey: ZQULGQNNJUBPOZ-PSLIRLAXSA-N
• SMILES:
  ACDLabs 12.01: Fc2cc(F)c(CNC1(C(F)(F)F)CC1)cc2C3(C)N=C(SC(C3)C)N
  OpenEye OEToolkits 2.0.6: CC1CC(N=C(S1)N)(C)c2cc(c(cc2F)F)CNC3(CC3)C(F)(F)F
  CACTVS 3.385: C[C@@H]1C[C@](C)(N=C(N)S1)c2cc(CNC3(CC3)C(F)(F)F)c(F)cc2F
  OpenEye OEToolkits 2.0.6: C[C@@H]1C[C@@](N=C(S1)N)(C)c2cc(c(cc2F)F)CNC3(CC3)C(F)(F)F
  CACTVS 3.385: C[CH]1C[C](C)(N=C(N)S1)c2cc(CNC3(CC3)C(F)(F)F)c(F)cc2F
• Formula: C17 H20 F5 N3 S
• Name: (4S,6R)-4-[2,4-difluoro-5-({[1-(trifluoromethyl)cyclopropyl]amino}methyl)phenyl]-4,6-dimethyl-5,6-dihydro-4H-1,3-thiazin-2-amine
• ChEMBL: CHEMBL4088234
• ZINC: ZINC000584905686
• PDB chain: 5tfu Chain D Residue 603

Receptor-Ligand Complex Structure

Structure summary

• PDB: 5tfu Aminomethyl-Derived Beta Secretase (BACE1) Inhibitors: Engaging Gly230 without an Anilide Functionality.
• Resolution: 2.75 Å
• Binding residue (original residue number in PDB): F120 A209 E216 Q244 L248 D301 S304 A305
• Binding residue (residue number reindexed from 1): F76 A165 E172 Q200 L204 D257 S260 A261
• Annotation score: 1
• Binding affinity: BindingDB: IC50=334nM

Enzymatic activity

• Catalytic site (original residue number in PDB): T309 F436 C443
• Catalytic site (residue number reindexed from 1): T265 F392 C399
• 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:5tfu, PDBe:5tfu, PDBj:5tfu
• PDBsum: 5tfu
• PubMed: 27997172
• UniProt: P10635|CP2D6_HUMAN Cytochrome P450 2D6 (Gene Name=CYP2D6)