Target Binding Site Detail

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Target General Information
Ligand General Information
Drug Binding Sites of Target
References
Target General Information  Top
Target ID T79031 Target Info
Target Name Beta-secretase 1 (BACE1)
Synonyms Membrane-associated aspartic protease 2; Memapsin-2; KIAA1149; Beta-site amyloid precursor protein cleaving enzyme 1; Beta-site APP cleaving enzyme 1; BACE; Aspartyl protease 2; Asp 2; ASP2
Target Type Clinical trial Target
Gene Name BACE1
Biochemical Class Peptidase
UniProt ID
BACE1_HUMAN
Ligand General Information  Top
Ligand Name (3r,4s,5s)-3-[(3-Tert-Butylbenzyl)amino]-5-{[3-(2,2-Difluoroethyl)-1h-Indol-5-Yl]methyl}tetrahydro-2h-Thiopyran-4-Ol 1,1-Dioxide Ligand Info
Canonical SMILES CC(C)(C)C1=CC=CC(=C1)CNC2CS(=O)(=O)CC(C2O)CC3=CC4=C(C=C3)NC=C4CC(F)F
InChI 1S/C27H34F2N2O3S/c1-27(2,3)21-6-4-5-18(10-21)13-30-24-16-35(33,34)15-20(26(24)32)9-17-7-8-23-22(11-17)19(14-31-23)12-25(28)29/h4-8,10-11,14,20,24-26,30-32H,9,12-13,15-16H2,1-3H3/t20-,24+,26+/m1/s1
InChIKey OOZZVYSXZBAROL-PSUQPPDWSA-N
PubChem Compound ID 57387067
Drug Binding Sites of Target  Top
PDB ID: 3VG1      Crystal Structure of Human Beta Secretase in Complex with NVP-BUR436, derived from a soaking experiment
Method X-ray diffraction Resolution 1.77 Å Mutation No [1]
PDB Sequence
SFVEMVDNLR
7
GKSGQGYYVE
17
MTVGSPPQTL
27
NILVDTGSSN
37
FAVGAAPHPF
47

LHRYYQRQLS
57
STYRDLRKGV
67
YVPYTQGKWE
77
GELGTDLVSI
87
PHGPNVTVRA
97

NIAAITESDK
107
FFINGSNWEG
117
ILGLAYAEIA
127
RPDDSLEPFF
137
DSLVKQTHVP
147

NLFSLQLCGA
157
VGGSMIIGGI
167
DHSLYTGSLW
177
YTPIRREWYY
187
EVIIVRVEIN
197

GQDLKMDCKE
207
YNYDKSIVDS
217
GTTNLRLPKK
227
VFEAAVKSIK
237
AASSTEKFPD
247

GFWLGEQLVC
257
WQAGTTPWNI
267
FPVISLYLMG
277
EVTNQSFRIT
287
ILPQQYLRPV
297

EDVATSQDDC
307
YKFAISQSST
317
GTVMGAVIME
327
GFYVVFDRAR
337
KRIGFAVSAC
347

HVHDEFRTAA
357
VEGPFVTLDM
367
EDCGYN
Residue
Distance (Å)
GLY11
3.337
GLN12
3.921
GLY13
3.531
LEU30
3.588
ASP32
2.524
GLY34
2.965
SER35
3.588
VAL69
3.571
PRO70
3.437
TYR71
3.328
THR72
2.931
GLN73
3.641
LYS107
4.499
Residue
Distance (Å)
PHE108
2.884
ILE110
3.414
TRP115
3.526
ILE118
4.015
ILE126
3.616
ARG128
3.848
TYR186
3.818
ILE214
4.126
ASP216
2.756
GLY218
3.125
THR219
3.051
THR220
3.118
ARG223
2.764
PDB ID: 4D83      Crystal Structure of Human Beta Secretase in Complex with NVP-BUR436, derived from a co-crystallization experiment
Method X-ray diffraction Resolution 2.40 Å Mutation No [1]
PDB Sequence
SFVEMVDNLR
7
GKSGQGYYVE
17
MTVGSPPQTL
27
NILVDTGSSN
37
FAVGAAPHPF
47

LHRYYQRQLS
57
STYRDLRKGV
67
YVPYTQGKWE
77
GELGTDLVSI
87
PHGPNVTVRA
97

NIAAITESDK
107
FFINGSNWEG
117
ILGLAYAEIA
127
RPDDSLEPFF
137
DSLVKQTHVP
147

NLFSLQLCGA
157
SVGGSMIIGG
167
IDHSLYTGSL
177
WYTPIRREWY
187
YEVIIVRVEI
197

NGQDLKMDCK
207
EYNYDKSIVD
217
SGTTNLRLPK
227
KVFEAAVKSI
237
KAASSTEKFP
247

DGFWLGEQLV
257
CWQAGTTPWN
267
IFPVISLYLM
277
GEVTNQSFRI
287
TILPQQYLRP
297

VEDVATSQDD
307
CYKFAISQSS
317
TGTVMGAVIM
327
EGFYVVFDRA
337
RKRIGFAVSA
347

CHVHDEFRTA
357
AVEGPFVTLD
367
MEDCGYN
Residue
Distance (Å)
GLY11
3.631
GLN12
2.912
GLY13
3.031
LEU30
3.769
ASP32
2.667
GLY34
2.942
SER35
3.600
VAL69
3.556
PRO70
3.290
TYR71
3.355
THR72
2.919
GLN73
3.532
LYS107
4.708
Residue
Distance (Å)
PHE108
2.870
ILE110
3.437
TRP115
3.799
ILE118
3.827
ILE126
3.723
ARG128
3.811
TYR187
3.713
ILE215
3.982
ASP217
2.685
GLY219
3.290
THR220
3.040
THR221
3.271
ARG224
2.914
References  Top
REF 1 Discovery of cyclic sulfone hydroxyethylamines as potent and selective beta-site APP-cleaving enzyme 1 (BACE1) inhibitors: structure-based design and in vivo reduction of amyloid beta-peptides. J Med Chem. 2012 Apr 12;55(7):3364-86.

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