Structure of PDB 3skf Chain A Binding Site BS01

Receptor Information

>3skf Chain A (length=387) Species: 9606 (Homo sapiens)

FVEMVDNLRGKSGQGYYVEMTVGSPPQTLNILVDTGSSNFAVGAAPHPFL
HRYYQRQLSSTYRDLRKGVYVPYTQGKWEGELGTDLVSIPHGPNVTVRAN
IAAITESDKFFINGSNWEGILGLAYAEIARPDDSLEPFFDSLVKQTHVPN
LFSLQLCGAGFPLNQSEVLASVGGSMIIGGIDHSLYTGSLWYTPIRREWY
YEVIIVRVEINGQDLKMDCKEYNYDKSIVDSGTTNLRLPKKVFEAAVKSI
KAASSTEKFPDGFWLGEQLVCWQAGTTPWNIFPVISLYLMGEVTNQSFRI
TILPQQYLRPVEDVATSQDDCYKFAISQSSTGTVMGAVIMEGFYVVFDRA
RKRIGFAVSACHVHDEFRTAAVEGPFVTLDMEDCGYN

Ligand information

• Ligand ID: PB7
• InChI: InChI=1S/C38H50N4O5/c1-5-27(2)38(41-28(3)43)21-22-42(37(38)46)34(20-19-29-13-8-6-9-14-29)36(45)40-33(24-30-15-10-7-11-16-30)35(44)26-39-25-31-17-12-18-32(23-31)47-4/h6-18,23,27,33-35,39,44H,5,19-22,24-26H2,1-4H3,(H,40,45)(H,41,43)/t27-,33-,34-,35+,38-/m0/s1
• InChIKey: SMPAHDBHYSCFQF-SXXDCNOLSA-N
• SMILES:
  CACTVS 3.370: CC[CH](C)[C]1(CCN([CH](CCc2ccccc2)C(=O)N[CH](Cc3ccccc3)[CH](O)CNCc4cccc(OC)c4)C1=O)NC(C)=O
  ACDLabs 12.01: O=C(NC(Cc1ccccc1)C(O)CNCc2cccc(OC)c2)C(N3C(=O)C(NC(=O)C)(CC3)C(C)CC)CCc4ccccc4
  CACTVS 3.370: CC[C@H](C)[C@]1(CCN([C@@H](CCc2ccccc2)C(=O)N[C@@H](Cc3ccccc3)[C@H](O)CNCc4cccc(OC)c4)C1=O)NC(C)=O
  OpenEye OEToolkits 1.7.2: CC[C@H](C)[C@]1(CCN(C1=O)[C@@H](CCc2ccccc2)C(=O)N[C@@H](Cc3ccccc3)[C@@H](CNCc4cccc(c4)OC)O)NC(=O)C
  OpenEye OEToolkits 1.7.2: CCC(C)C1(CCN(C1=O)C(CCc2ccccc2)C(=O)NC(Cc3ccccc3)C(CNCc4cccc(c4)OC)O)NC(=O)C
• Formula: C38 H50 N4 O5
• Name: (2S)-2-{(3S)-3-(acetylamino)-3-[(2S)-butan-2-yl]-2-oxopyrrolidin-1-yl}-N-{(2S,3R)-3-hydroxy-4-[(3-methoxybenzyl)amino]-1-phenylbutan-2-yl}-4-phenylbutanamide
• ZINC: ZINC000073161310
• PDB chain: 3skf Chain A Residue 394

Receptor-Ligand Complex Structure

Structure summary

• PDB: 3skf Synthesis and in vivo evaluation of cyclic diaminopropane BACE-1 inhibitors.
• Resolution: 3.0 Å
• Binding residue (original residue number in PDB): G11 Q12 D32 G34 S35 P70 Y71 T72 Q73 F108 D228 G230 T231 T232
• Binding residue (residue number reindexed from 1): G13 Q14 D34 G36 S37 P72 Y73 T74 Q75 F110 D230 G232 T233 T234
• Annotation score: 1
• Binding affinity: PDBbind-CN: -logKd/Ki=8.30,IC50=5nM

Enzymatic activity

• Catalytic site (original residue number in PDB): D32 S35 N37 A39 Y71 D228 T231
• Catalytic site (residue number reindexed from 1): D34 S37 N39 A41 Y73 D230 T233
• 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:3skf, PDBe:3skf, PDBj:3skf
• PDBsum: 3skf
• PubMed: 21974952
• UniProt: P56817|BACE1_HUMAN Beta-secretase 1 (Gene Name=BACE1)