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 (2r,4s)-N-Butyl-4-[(2s,5s,7r)-2,7-Dimethyl-3,15-Dioxo-1,4-Diazacyclopentadecan-5-Yl]-4-Hydroxy-2-Methylbutanamide Ligand Info
Canonical SMILES CCCCNC(=O)C(C)CC(C1CC(CCCCCCCC(=O)NC(C(=O)N1)C)C)O
InChI 1S/C24H45N3O4/c1-5-6-14-25-23(30)18(3)16-21(28)20-15-17(2)12-10-8-7-9-11-13-22(29)26-19(4)24(31)27-20/h17-21,28H,5-16H2,1-4H3,(H,25,30)(H,26,29)(H,27,31)/t17-,18-,19+,20+,21+/m1/s1
InChIKey ZUIGWVKXPZANDI-MJCUULBUSA-N
PubChem Compound ID 25163981
Drug Binding Sites of Target  Top
PDB ID: 3DV1      Crystal structure of human beta-secretase in complex with NVP-ARV999
Method X-ray diffraction Resolution 2.10 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
178
IDHSLYTGSL
188
WYTPIRREWY
198
YEVIIVRVEI
208

NGQDLKMDCK
218
EYNYDKSIVD
228
SGTTNLRLPK
238
KVFEAAVKSI
248
KAASSTEKFP
258

DGFWLGEQLV
268
CWQAGTTPWN
278
IFPVISLYLM
288
GEVTNQSFRI
298
TILPQQYLRP
308

VEDVATSQDD
318
CYKFAISQSS
328
TGTVMGAVIM
338
EGFYVVFDRA
348
RKRIGFAVSA
358

CHVHDEFRTA
368
AVEGPFVTLD
378
MEDCGYN
Residue
Distance (Å)
GLY11
4.048
GLN12
3.611
GLY13
3.769
LEU30
3.449
ASP32
2.503
GLY34
2.868
SER35
4.103
VAL69
3.857
PRO70
3.767
TYR71
3.170
THR72
2.979
GLN73
3.039
PHE108
3.772
Residue
Distance (Å)
ILE110
3.770
TRP115
3.972
ILE118
4.354
ILE126
3.737
ARG128
4.162
TYR198
3.670
ILE226
4.005
ASP228
2.603
GLY230
3.019
THR231
3.460
THR232
2.933
ASN233
4.614
PDB ID: 5QCW      Crystal structure of BACE complex with BMC021
Method X-ray diffraction Resolution 2.10 Å Mutation No [2]
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
178
IDHSLYTGSL
188
WYTPIRREWY
198
YEVIIVRVEI
208

NGQDLKMDCK
218
EYNYDKSIVD
228
SGTTNLRLPK
238
KVFEAAVKSI
248
KAASSTEKFP
258

DGFWLGEQLV
268
CWQAGTTPWN
278
IFPVISLYLM
288
GEVTNQSFRI
298
TILPQQYLRP
308

VEDVATSQDD
318
CYKFAISQSS
328
TGTVMGAVIM
338
EGFYVVFDRA
348
RKRIGFAVSA
358

CHVHDEFRTA
368
AVEGPFVTLD
378
MEDCGYN
Residue
Distance (Å)
GLY11
3.793
GLN12
3.550
GLY13
3.671
LEU30
3.680
ASP32
2.522
GLY34
2.842
SER35
3.916
VAL69
3.990
PRO70
3.701
TYR71
3.163
THR72
2.944
GLN73
3.040
PHE108
3.698
Residue
Distance (Å)
ILE110
3.878
TRP115
3.993
ILE118
4.274
ILE126
3.834
ARG128
4.001
TYR198
3.772
ILE226
3.919
ASP228
2.575
GLY230
2.961
THR231
3.477
THR232
2.880
ASN233
4.540
ARG235
4.915
References  Top
REF 1 Macrocyclic peptidomimetic beta-secretase (BACE-1) inhibitors with activity in vivo. Bioorg Med Chem Lett. 2009 Mar 1;19(5):1366-70.
REF 2 D3R grand challenge 4: blind prediction of protein-ligand poses, affinity rankings, and relative binding free energies. J Comput Aided Mol Des. 2020 Feb;34(2):99-119.

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