Structure of PDB 6bfx Chain B Binding Site BS01

Receptor Information

>6bfx Chain B (length=388) Species: 9606 (Homo sapiens)

SFVEMVDNLRGKSGQGYYVEMTVGSPPQTLNILVDTGSSNFAVGAAPHPF
LHRYYQRQLSSTYRDLRKGVYVPYTQGKWEGELGTDLVSIPHGPNVTVRA
NIAAITESDKFFINGSNWEGILGLAYAEIARPDDSLEPFFDSLVKQTHVP
NLFSLQLCGAGFPLNQSEVLASVGGSMIIGGIDHSLYTGSLWYTPIRREW
YYEVIIVRVEINGQDLKMDCKEYNYDKSIVDSGTTNLRLPKKVFEAAVKS
IKAASSTEKFPDGFWLGEQLVCWQAGTTPWNIFPVISLYLMGEVTNQSFR
ITILPQQYLRPVEDVATSQDDCYKFAISQSSTGTVMGAVIMEGFYVVFDR
ARKRIGFAVSACHVHDEFRTAAVEGPFVTLDMEDCGYN

Ligand information

• Ligand ID: DKJ
• InChI: InChI=1S/C21H32F2N2O4/c1-12-20(29-11-21(3,4)5)28-10-18(24-12)19(27)17(25-13(2)26)8-14-6-15(22)9-16(23)7-14/h6-7,9,12,17-20,24,27H,8,10-11H2,1-5H3,(H,25,26)/t12-,17-,18+,19-,20-/m0/s1
• InChIKey: MTSIVXGKWLWPKB-VVEMMYRFSA-N
• SMILES:
  CACTVS 3.385: C[CH]1N[CH](CO[CH]1OCC(C)(C)C)[CH](O)[CH](Cc2cc(F)cc(F)c2)NC(C)=O
  OpenEye OEToolkits 2.0.6: CC1C(OCC(N1)C(C(Cc2cc(cc(c2)F)F)NC(=O)C)O)OCC(C)(C)C
  OpenEye OEToolkits 2.0.6: C[C@H]1[C@@H](OC[C@@H](N1)[C@H]([C@H](Cc2cc(cc(c2)F)F)NC(=O)C)O)OCC(C)(C)C
  CACTVS 3.385: C[C@@H]1N[C@H](CO[C@H]1OCC(C)(C)C)[C@@H](O)[C@H](Cc2cc(F)cc(F)c2)NC(C)=O
  ACDLabs 12.01: O=C(C)NC(Cc1cc(cc(c1)F)F)C(C2NC(C)C(OC2)OCC(C)(C)C)O
• Formula: C21 H32 F2 N2 O4
• Name: N-{(1S,2S)-3-(3,5-difluorophenyl)-1-[(3R,5S,6R)-6-(2,2-dimethylpropoxy)-5-methylmorpholin-3-yl]-1-hydroxypropan-2-yl}acetamide
• ChEMBL: CHEMBL4116547
• ZINC: ZINC000038216060
• PDB chain: 6bfx Chain B Residue 401

Receptor-Ligand Complex Structure

Structure summary

• PDB: 6bfx Optimization of Hydroxyethylamine Transition State Isosteres as Aspartic Protease Inhibitors by Exploiting Conformational Preferences.
• Resolution: 1.99 Å
• Binding residue (original residue number in PDB): D32 G34 S35 Y71 T72 F108 Y198 D228 G230
• Binding residue (residue number reindexed from 1): D35 G37 S38 Y74 T75 F111 Y201 D231 G233
• Annotation score: 1
• Binding affinity: MOAD: ic50=0.079uM

Enzymatic activity

• Catalytic site (original residue number in PDB): D32 S35 N37 A39 Y71 D228 T231
• Catalytic site (residue number reindexed from 1): D35 S38 N40 A42 Y74 D231 T234
• Enzyme Commision number: 3.4.23.46: memapsin 2.

Gene Ontology

Molecular Function

• GO:0004190 aspartic-type endopeptidase activity

Biological Process

• GO:0006508 proteolysis

Cellular Component

• GO:0016020 membrane

External links

• PDB: RCSB:6bfx, PDBe:6bfx, PDBj:6bfx
• PDBsum: 6bfx
• PubMed: 29088532
• UniProt: P56817|BACE1_HUMAN Beta-secretase 1 (Gene Name=BACE1)