Structure of PDB 3ivi Chain B Binding Site BS01

Receptor Information

>3ivi Chain B (length=378) Species: 9606 (Homo sapiens)

SFVEMVDNLRGKSGQGYYVEMTVGSPPQTLNILVDTGSSNFAVGAAPHPF
LHRYYQRQLSSTYRDLRKGVYVPYTQGKWEGELGTDLVSIPHGPNVTVRA
NIAAITESDKFFINGSNWEGILGLAYAEIARPDDSLEPFFDSLVKQTHVP
NLFSLQLCGAGFPLNSVGGSMIIGGIDHSLYTGSLWYTPIRREWYYEVII
VRVEINGQDLKMDCKEYNYDKSIVDSGTTNLRLPKKVFEAAVKSIKAASS
TEKFPDGFWLGEQLVCWQAGTTPWNIFPVISLYLMGEVTNQSFRITILPQ
QYLRPVEDDDCYKFAISQSSTGTVMGAVIMEGFYVVFDRARKRIGFAVSA
CHVHDEFRTAAVEGPFVTLDMEDCGYNI

Ligand information

• Ligand ID: 2LI
• InChI: InChI=1S/C29H36F2N4O2/c1-18(36)34-26(12-19-10-23(30)14-24(31)11-19)27(37)17-32-29(9-8-25-20(15-29)16-33-35-25)22-7-5-6-21(13-22)28(2,3)4/h5-7,10-11,13-14,16,26-27,32,37H,8-9,12,15,17H2,1-4H3,(H,33,35)(H,34,36)/t26-,27+,29-/m0/s1
• InChIKey: BAILJXDQIBWAPX-GKRYNVPLSA-N
• SMILES:
  CACTVS 3.352: CC(=O)N[CH](Cc1cc(F)cc(F)c1)[CH](O)CN[C]2(CCc3[nH]ncc3C2)c4cccc(c4)C(C)(C)C
  OpenEye OEToolkits 1.7.0: CC(=O)NC(Cc1cc(cc(c1)F)F)C(CNC2(CCc3c(cn[nH]3)C2)c4cccc(c4)C(C)(C)C)O
  OpenEye OEToolkits 1.7.0: CC(=O)N[C@@H](Cc1cc(cc(c1)F)F)[C@@H](CN[C@]2(CCc3c(cn[nH]3)C2)c4cccc(c4)C(C)(C)C)O
  ACDLabs 11.02: Fc1cc(cc(F)c1)CC(NC(=O)C)C(O)CNC4(c2cccc(c2)C(C)(C)C)CCc3c(cnn3)C4
  CACTVS 3.352: CC(=O)N[C@@H](Cc1cc(F)cc(F)c1)[C@H](O)CN[C@]2(CCc3[nH]ncc3C2)c4cccc(c4)C(C)(C)C
• Formula: C29 H36 F2 N4 O2
• Name: N-[(1S,2R)-3-{[(5S)-5-(3-tert-butylphenyl)-4,5,6,7-tetrahydro-1H-indazol-5-yl]amino}-1-(3,5-difluorobenzyl)-2-hydroxypropyl]acetamide
• ZINC: ZINC000044683480
• PDB chain: 3ivi Chain B Residue 2

Receptor-Ligand Complex Structure

Structure summary

• PDB: 3ivi Design and synthesis of cell potent BACE-1 inhibitors: structure-activity relationship of P1' substituents.
• Resolution: 2.2 Å
• Binding residue (original residue number in PDB): D93 G95 S96 Y132 T133 F169 Y259 K285 I287 D289 G291 T390 V393
• Binding residue (residue number reindexed from 1): D35 G37 S38 Y74 T75 F111 Y195 K221 I223 D225 G227 T321 V324
• Annotation score: 1
• Binding affinity: MOAD: ic50=12nM

Enzymatic activity

• Catalytic site (original residue number in PDB): D93 S96 N98 A100 Y132 D289 T292
• Catalytic site (residue number reindexed from 1): D35 S38 N40 A42 Y74 D225 T228
• 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:3ivi, PDBe:3ivi, PDBj:3ivi
• PDBsum: 3ivi
• PubMed: 19811916
• UniProt: P56817|BACE1_HUMAN Beta-secretase 1 (Gene Name=BACE1)