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 (3s,4s,5r)-3-(4-Amino-3-{[(2r)-3-Ethoxy-1,1,1-Trifluoropropan-2-Yl]oxy}-5-Fluorobenzyl)-5-[(3-Tert-Butylbenzyl)amino]tetrahydro-2h-Thiopyran-4-Ol 1,1-Dioxide Ligand Info
Canonical SMILES CCOCC(C(F)(F)F)OC1=C(C(=CC(=C1)CC2CS(=O)(=O)CC(C2O)NCC3=CC(=CC=C3)C(C)(C)C)F)N
InChI 1S/C28H38F4N2O5S/c1-5-38-14-24(28(30,31)32)39-23-12-18(11-21(29)25(23)33)9-19-15-40(36,37)16-22(26(19)35)34-13-17-7-6-8-20(10-17)27(2,3)4/h6-8,10-12,19,22,24,26,34-35H,5,9,13-16,33H2,1-4H3/t19-,22+,24-,26+/m1/s1
InChIKey UJZFSYZNJMWXJO-NJONLQHESA-N
PubChem Compound ID 44625397
Drug Binding Sites of Target  Top
PDB ID: 4D89      Crystal Structure of Human Beta Secretase in Complex with NVP-BXD552, derived from a soaking experiment
Method X-ray diffraction Resolution 1.65 Å Mutation No [1]
PDB Sequence
SFVEMVDNLR
55
GKSGQGYYVE
65
MTVGSPPQTL
75
NILVDTGSSN
85
FAVGAAPHPF
95

LHRYYQRQLS
105
STYRDLRKGV
115
YVPYTQGKWE
125
GELGTDLVSI
135
PHGPNVTVRA
145

NIAAITESDK
155
FFINGSNWEG
165
ILGLAYAEIA
175
RPDDSLEPFF
185
DSLVKQTHVP
195

NLFSLQLCGA
205
GGSMIIGGID
228
HSLYTGSLWY
238
TPIRREWYYE
248
VIIVRVEING
258

QDLKMDCKEY
268
NYDKSIVDSG
278
TTNLRLPKKV
288
FEAAVKSIKA
298
ASSTEKFPDG
308

FWLGEQLVCW
318
QAGTTPWNIF
328
PVISLYLMGE
338
VTNQSFRITI
348
LPQQYLRPVE
358

DVATSQDDCY
368
KFAISQSSTG
378
TVMGAVIMEG
388
FYVVFDRARK
398
RIGFAVSACH
408

VHDEFRTAAV
418
EGPFVTLDME
428
DCGYN
Residue
Distance (Å)
GLY59
3.647
GLN60
2.896
GLY61
3.018
LEU78
3.285
ASP80
2.666
GLY82
2.937
SER83
3.611
VAL117
3.663
PRO118
3.372
TYR119
3.381
THR120
2.970
GLN121
3.234
GLY122
3.796
LYS123
4.859
LYS155
3.899
Residue
Distance (Å)
PHE156
2.785
PHE157
4.992
ILE158
3.862
TRP163
3.707
ILE166
4.054
ILE174
3.616
ARG176
3.719
TYR246
3.797
ILE274
4.114
ASP276
2.680
GLY278
3.063
THR279
3.094
THR280
3.421
ARG283
4.932
PDB ID: 4D8C      Crystal Structure of Human Beta Secretase in Complex with NVP-BXD552, derived from a co-crystallization experiment
Method X-ray diffraction Resolution 2.07 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
3.774
GLN12
2.827
GLY13
3.217
LEU30
3.305
ASP32
2.658
GLY34
2.947
SER35
3.564
VAL69
3.572
PRO70
3.452
TYR71
3.365
THR72
2.946
GLN73
3.153
GLY74
3.727
LYS75
4.783
Residue
Distance (Å)
LYS107
3.807
PHE108
2.869
ILE110
3.541
TRP115
3.998
ILE118
3.952
ILE126
3.759
ARG128
3.696
TYR187
3.661
ILE215
3.991
ASP217
2.675
GLY219
3.054
THR220
3.136
THR221
3.436
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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