Structure of PDB 6wny Chain A Binding Site BS01

Receptor Information

>6wny Chain A (length=380) Species: 9606 (Homo sapiens)

FVEMVDNLRGKSGQGYYVEMTVGSPPQTLNILVDTGSSNFAVGAAPHPFL
HRYYQRQLSSTYRDLRKGVYVPYTQGKWEGELGTDLVSIPHGPNVTVRAN
IAAITESDKFFINGSNWEGILGLAYAEIARPDDSLEPFFDSLVKQTHVPN
LFSLQLCGAGFASVGGSMIIGGIDHSLYTGSLWYTPIRREWYYEVIIVRV
EINGQDLKMDCKEYNYDKSIVDSGTTNLRLPKKVFEAAVKSIKAASSTEK
FPDGFWLGEQLVCWQAGTTPWNIFPVISLYLMGEVTNQSFRITILPQQYL
RPVEDVATSQDDCYKFAISQSSTGTVMGAVIMEGFYVVFDRARKRIGFAV
SACHVHDEFRTAAVEGPFVTLDMEDCGYNI

Ligand information

• Ligand ID: U64
• InChI: InChI=1S/C25H23F2N5O2S/c1-24(21-12-25(21,35-23(29)31-24)22(33)32-6-8-34-9-7-32)17-10-15(2-4-18(17)26)11-19(27)20-5-3-16(13-28)14-30-20/h2-5,10-11,14,21H,6-9,12H2,1H3,(H2,29,31)/b19-11-/t21-,24+,25-/m0/s1
• InChIKey: VZHFJCNPAIRJSA-MYMUPAQMSA-N
• SMILES:
  ACDLabs 12.01: c4(cc(C1(C)C2C(SC(=N1)N)(C2)C(=O)N3CCOCC3)c(F)cc4)[C@H]=C(F)c5ccc(cn5)C#N
  CACTVS 3.385: C[C@@]1(N=C(N)S[C@]2(C[C@@H]12)C(=O)N3CCOCC3)c4cc(ccc4F)\C=C(/F)c5ccc(cn5)C#N
  OpenEye OEToolkits 2.0.7: CC1(C2CC2(SC(=N1)N)C(=O)N3CCOCC3)c4cc(ccc4F)C=C(c5ccc(cn5)C#N)F
  CACTVS 3.385: C[C]1(N=C(N)S[C]2(C[CH]12)C(=O)N3CCOCC3)c4cc(ccc4F)C=C(F)c5ccc(cn5)C#N
  OpenEye OEToolkits 2.0.7: C[C@]1([C@@H]2C[C@@]2(SC(=N1)N)C(=O)N3CCOCC3)c4cc(ccc4F)/C=C(/c5ccc(cn5)C#N)\F
• Formula: C25 H23 F2 N5 O2 S
• Name: 6-[(Z)-2-{3-[(1S,5S,6S)-3-amino-5-methyl-1-(morpholine-4-carbonyl)-2-thia-4-azabicyclo[4.1.0]hept-3-en-5-yl]-4-fluorophenyl}-1-fluoroethenyl]pyridine-3-carbonitrile
• ChEMBL: CHEMBL4760458
• PDB chain: 6wny Chain A Residue 501

Receptor-Ligand Complex Structure

Structure summary

• PDB: 6wny The development of a structurally distinct series of BACE1 inhibitors via the (Z)-fluoro-olefin amide bioisosteric replacement.
• Resolution: 1.86 Å
• Binding residue (original residue number in PDB): G72 Q73 G74 D93 G95 Y132 F169 I179 Y259 D289 G291 T293
• Binding residue (residue number reindexed from 1): G13 Q14 G15 D34 G36 Y73 F110 I120 Y192 D222 G224 T226
• Annotation score: 1
• Binding affinity: MOAD: ic50=0.0015uM
  BindingDB: IC50=1.73nM

Enzymatic activity

• Catalytic site (original residue number in PDB): D93 S96 N98 A100 Y132 D289 T292
• Catalytic site (residue number reindexed from 1): D34 S37 N39 A41 Y73 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:6wny, PDBe:6wny, PDBj:6wny
• PDBsum: 6wny
• PubMed: 32527542
• UniProt: P56817|BACE1_HUMAN Beta-secretase 1 (Gene Name=BACE1)