Structure of PDB 5he5 Chain B Binding Site BS01

Receptor Information

>5he5 Chain B (length=387) Species: 9606 (Homo sapiens)

RGSFVEMVDNLRGKSGQGYYVEMTVGSPPQTLNILVDTGSSNFAVGAAPH
PFLHRYYQRQLSSTYRDLRKGVYVPYTQGKWEGELGTDLVSIPHGPNVTV
RANIAAITESDKFFINGSNWEGILGLAYAEIARPDDSLEPFFDSLVKQTH
VPNLFSLQLCGAGFPLNQSEVLASVGGSMIIGGIDHSLYTGSLWYTPIRR
EWYYEVIIVRVEINGQDLKMDCKEYNYDKSIVDSGTTNLRLPKKVFEAAV
KSIKAASSTEKFPDGFWLGEQLVCWQAGTTPWNIFPVISLYLMGEVTNQS
FRITILPQQYLRPVEDSQDDCYKFAISQSSTGTVMGAVIMEGFYVVFDRA
RKRIGFAVSACHVHDEFRTAAVEGPFVTLDMEDCGYN

Ligand information

• Ligand ID: 60S
• InChI: InChI=1S/C18H19FN8OS/c1-9-13(19)14(22-2)24-17(23-9)27-7-11-15(28)26(3)16(21)25-18(11,8-27)12-5-4-10(6-20)29-12/h4-5,11H,7-8H2,1-3H3,(H2,21,25)(H,22,23,24)/t11-,18-/m0/s1
• InChIKey: ZGUINBOSNMEMBB-VOJFVSQTSA-N
• SMILES:
  CACTVS 3.385: CNc1nc(nc(C)c1F)N2C[CH]3C(=O)N(C)C(=N)N[C]3(C2)c4sc(cc4)C#N
  ACDLabs 12.01: C32(C(CN(c1nc(NC)c(F)c(n1)C)C2)C(=O)N(\C(=N)N3)C)c4sc(cc4)C#N
  OpenEye OEToolkits 2.0.4: Cc1c(c(nc(n1)N2CC3C(=O)N(C(=N)NC3(C2)c4ccc(s4)C#N)C)NC)F
  OpenEye OEToolkits 2.0.4: [H]/N=C/1\N[C@]2(CN(C[C@H]2C(=O)N1C)c3nc(c(c(n3)NC)F)C)c4ccc(s4)C#N
  CACTVS 3.385: CNc1nc(nc(C)c1F)N2C[C@H]3C(=O)N(C)C(=N)N[C@]3(C2)c4sc(cc4)C#N
• Formula: C18 H19 F N8 O S
• Name: 5-{(2E,4aR,7aR)-6-[5-fluoro-4-methyl-6-(methylamino)pyrimidin-2-yl]-2-imino-3-methyl-4-oxooctahydro-7aH-pyrrolo[3,4-d]pyrimidin-7a-yl}thiophene-2-carbonitrile
• ChEMBL: CHEMBL3799879
• ZINC: ZINC000584905342
• PDB chain: 5he5 Chain B Residue 502

Receptor-Ligand Complex Structure

Structure summary

• PDB: 5he5 Structure-Based Design of an Iminoheterocyclic beta-Site Amyloid Precursor Protein Cleaving Enzyme (BACE) Inhibitor that Lowers Central A beta in Nonhuman Primates.
• Resolution: 1.55 Å
• Binding residue (original residue number in PDB): L91 D93 S96 V130 Y132 F169 W176 R189 D289 G291
• Binding residue (residue number reindexed from 1): L35 D37 S40 V74 Y76 F113 W120 R133 D233 G235
• Annotation score: 1
• Binding affinity: MOAD: Ki=336nM
  BindingDB: IC50=157nM,Ki=336nM

Enzymatic activity

• Catalytic site (original residue number in PDB): D93 S96 N98 A100 Y132 D289 T292
• Catalytic site (residue number reindexed from 1): D37 S40 N42 A44 Y76 D233 T236
• 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:5he5, PDBe:5he5, PDBj:5he5
• PDBsum: 5he5
• PubMed: 26937601
• UniProt: P56817|BACE1_HUMAN Beta-secretase 1 (Gene Name=BACE1)