Structure of PDB 4dpf Chain A Binding Site BS01

Receptor Information

>4dpf Chain A (length=375) Species: 9606 (Homo sapiens)

FVEMVDNLRGKSGQGYYVEMTVGSPPQTLNILVDTGSSNFAVGAAPHPFL
HRYYQRQLSSTYRDLRKGVYVPYTQGKWEGELGTDLVSIPHGPNVTVRAN
IAAITESDKFFINGSNWEGILGLAYAEIARPDDSLEPFFDSLVKQTHVPN
LFSLQLCGAVGGSMIIGGIDHSLYTGSLWYTPIRREWYYEVIIVRVEING
QDLKMDCKEYNYDKSIVDSGTTNLRLPKKVFEAAVKSIKAASSTEKFPDG
FWLGEQLVCWQAGTTPWNIFPVISLYLMGEVTNQSFRITILPQQYLRPVE
DVATSQDDCYKFAISQSSTGTVMGAVIMEGFYVVFDRARKRIGFAVSACH
VHDEFRTAAVEGPFVTLDMEDCGYN

Ligand information

• Ligand ID: 0LG
• InChI: InChI=1S/C35H44N4O6S/c1-24(2)27-14-10-11-25(17-27)21-36-22-33(40)32-23-45-16-9-8-15-31(26-12-6-5-7-13-26)37-34(41)28-18-29(35(42)38-32)20-30(19-28)39(3)46(4,43)44/h5-14,17-20,24,31-33,36,40H,15-16,21-23H2,1-4H3,(H,37,41)(H,38,42)/b9-8+/t31-,32-,33+/m0/s1
• InChIKey: XYJDOUBLYLOJJL-YNYOQIOBSA-N
• SMILES:
  CACTVS 3.370: CC(C)c1cccc(CNC[C@@H](O)[C@@H]2COC\C=C\C[C@H](NC(=O)c3cc(cc(c3)C(=O)N2)N(C)[S](C)(=O)=O)c4ccccc4)c1
  ACDLabs 12.01: O=S(=O)(N(c1cc3cc(c1)C(=O)NC(COCC=CCC(c2ccccc2)NC3=O)C(O)CNCc4cccc(c4)C(C)C)C)C
  OpenEye OEToolkits 1.7.6: CC(C)c1cccc(c1)CNCC(C2COCC=CCC(NC(=O)c3cc(cc(c3)N(C)S(=O)(=O)C)C(=O)N2)c4ccccc4)O
  OpenEye OEToolkits 1.7.6: CC(C)c1cccc(c1)CNC[C@H]([C@@H]2COC/C=C/C[C@H](NC(=O)c3cc(cc(c3)N(C)S(=O)(=O)C)C(=O)N2)c4ccccc4)O
  CACTVS 3.370: CC(C)c1cccc(CNC[CH](O)[CH]2COCC=CC[CH](NC(=O)c3cc(cc(c3)C(=O)N2)N(C)[S](C)(=O)=O)c4ccccc4)c1
• Formula: C35 H44 N4 O6 S
• Name: N-[(4S,8E,11S)-4-[(1R)-1-hydroxy-2-{[3-(propan-2-yl)benzyl]amino}ethyl]-2,13-dioxo-11-phenyl-6-oxa-3,12-diazabicyclo[12.3.1]octadeca-1(18),8,14,16-tetraen-16-yl]-N-methylmethanesulfonamide
• ChEMBL: CHEMBL2047040
• ZINC: ZINC000084758523
• PDB chain: 4dpf Chain A Residue 500

Receptor-Ligand Complex Structure

Structure summary

• PDB: 4dpf Highly potent macrocyclic BACE-1 inhibitors incorporating a hydroxyethylamine core: design, synthesis and X-ray crystal structures of enzyme inhibitor complexes.
• Resolution: 1.8 Å
• Binding residue (original residue number in PDB): G59 Q60 L78 D80 G82 Y119 T120 Q121 I158 D276 G278 T279 T280 N281 R283
• Binding residue (residue number reindexed from 1): G13 Q14 L32 D34 G36 Y73 T74 Q75 I112 D218 G220 T221 T222 N223 R225
• Annotation score: 1
• Binding affinity: MOAD: ic50=400nM
  PDBbind-CN: -logKd/Ki=6.40,IC50=400nM

Enzymatic activity

• Catalytic site (original residue number in PDB): D80 S83 N85 A87 Y119 D276 T279
• Catalytic site (residue number reindexed from 1): D34 S37 N39 A41 Y73 D218 T221
• 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:4dpf, PDBe:4dpf, PDBj:4dpf
• PDBsum: 4dpf
• PubMed: 22698785
• UniProt: P56817|BACE1_HUMAN Beta-secretase 1 (Gene Name=BACE1)