Structure of PDB 4i0h Chain A Binding Site BS01

Receptor Information

>4i0h Chain A (length=374) Species: 9606 (Homo sapiens)

SFVEMVDNLRGKSGQGYYVEMTVGSPPQTLNILVDTGSSNFAVGAAPHPF
LHRYYQRQLSSTYRDLRKGVYVPYTQGKWEGELGTDLVSIPHGPNVTVRA
NIAAITESDKFFINGSNWEGILGLAYAEIARPDDSLEPFFDSLVKQTHVP
NLFSLQLCGAGASVGGSMIIGGIDHSLYTGSLWYTPIRREWYYEVIIVRV
EINGQDLKMDCKEYNYDKSIVDSGTTNLRLPKKVFEAAVKSIKAASSTEK
FPDGFWLGEQLVCWQAGTTPWNIFPVISLYLMGEVTNQSFRITILPQQYL
RPVEDDDCYKFAISQSSTGTVMGAVIMEGFYVVFDRARKRIGFAVSACHV
HDEFRTAAVEGPFVTLDMEDCGYN

Ligand information

• Ligand ID: 1BL
• InChI: InChI=1S/C31H42F2N2O5/c1-30(2,3)21-8-7-9-22(17-21)31(12-5-4-6-13-31)34-19-27(37)25(16-20-14-23(32)18-24(33)15-20)35-28(38)11-10-26(36)29(39)40/h7-9,14-15,17-18,25-27,34,36-37H,4-6,10-13,16,19H2,1-3H3,(H,35,38)(H,39,40)/t25-,26+,27+/m0/s1
• InChIKey: ZQBAKJWCBZPMKW-OYUWMTPXSA-N
• SMILES:
  OpenEye OEToolkits 1.7.6: CC(C)(C)c1cccc(c1)C2(CCCCC2)NCC(C(Cc3cc(cc(c3)F)F)NC(=O)CCC(C(=O)O)O)O
  CACTVS 3.370: CC(C)(C)c1cccc(c1)C2(CCCCC2)NC[CH](O)[CH](Cc3cc(F)cc(F)c3)NC(=O)CC[CH](O)C(O)=O
  CACTVS 3.370: CC(C)(C)c1cccc(c1)C2(CCCCC2)NC[C@@H](O)[C@H](Cc3cc(F)cc(F)c3)NC(=O)CC[C@@H](O)C(O)=O
  OpenEye OEToolkits 1.7.6: CC(C)(C)c1cccc(c1)C2(CCCCC2)NC[C@H]([C@H](Cc3cc(cc(c3)F)F)NC(=O)CC[C@H](C(=O)O)O)O
  ACDLabs 12.01: O=C(O)C(O)CCC(=O)NC(C(O)CNC2(c1cccc(c1)C(C)(C)C)CCCCC2)Cc3cc(F)cc(F)c3
• Formula: C31 H42 F2 N2 O5
• Name: (2R)-5-{[(2S,3R)-4-{[1-(3-tert-butylphenyl)cyclohexyl]amino}-1-(3,5-difluorophenyl)-3-hydroxybutan-2-yl]amino}-2-hydroxy-5-oxopentanoic acid
• ZINC: ZINC000098207940
• PDB chain: 4i0h Chain A Residue 501

Receptor-Ligand Complex Structure

Structure summary

• PDB: 4i0h SPR and structural analysis yield insight towards mechanism of inhibition of BACE inhibitors
• Resolution: 2.2 Å
• Binding residue (original residue number in PDB): D38 G40 S41 Y77 T78 F114 Y204 I232 D234 T238 T335
• Binding residue (residue number reindexed from 1): D35 G37 S38 Y74 T75 F111 Y192 I220 D222 T226 T318
• Annotation score: 1

Enzymatic activity

• Catalytic site (original residue number in PDB): D38 S41 N43 A45 Y77 D234 T237
• Catalytic site (residue number reindexed from 1): D35 S38 N40 A42 Y74 D222 T225
• 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:4i0h, PDBe:4i0h, PDBj:4i0h
• PDBsum: 4i0h
• UniProt: P56817|BACE1_HUMAN Beta-secretase 1 (Gene Name=BACE1)