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,5s)-N-Butyl-4-Hydroxy-2,7-Dimethyl-5-{[n-(4-Methylpentanoyl)-L-Methionyl]amino}octanamide Ligand Info
Canonical SMILES CCCCNC(=O)C(C)CC(C(CC(C)C)NC(=O)C(CCSC)NC(=O)CCC(C)C)O
InChI 1S/C25H49N3O4S/c1-8-9-13-26-24(31)19(6)16-22(29)21(15-18(4)5)28-25(32)20(12-14-33-7)27-23(30)11-10-17(2)3/h17-22,29H,8-16H2,1-7H3,(H,26,31)(H,27,30)(H,28,32)/t19-,20+,21+,22+/m1/s1
InChIKey XTRMRNMVFXWTCC-MLNNCEHLSA-N
PubChem Compound ID 25163980
Drug Binding Sites of Target  Top
PDB ID: 3DUY      Crystal structure of human beta-secretase in complex with NVP-AFJ144
Method X-ray diffraction Resolution 1.97 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

VDDCYKFAIS
325
QSSTGTVMGA
335
VIMEGFYVVF
345
DRARKRIGFA
355
VSACHVHDEF
365

RTAAVEGPFV
375
TLDMEDCGYN
385
Residue
Distance (Å)
GLY11
3.638
GLN12
3.967
GLY13
3.595
LEU30
3.825
ASP32
2.510
GLY34
2.850
SER35
4.028
VAL69
3.823
PRO70
3.820
TYR71
3.248
THR72
3.057
GLN73
2.997
PHE108
3.785
ILE110
4.120
Residue
Distance (Å)
TRP115
4.114
ILE118
4.227
ILE126
3.861
ARG128
3.942
TYR198
3.839
ILE226
3.936
ASP228
2.538
GLY230
3.022
THR231
3.365
THR232
2.905
ASN233
4.552
ARG235
3.617
SER325
4.239
PDB ID: 5QCQ      Crystal structure of BACE complex with BMC025
Method X-ray diffraction Resolution 1.97 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

VDDCYKFAIS
325
QSSTGTVMGA
335
VIMEGFYVVF
345
DRARKRIGFA
355
VSACHVHDEF
365

RTAAVEGPFV
375
TLDMEDCGYN
385
Residue
Distance (Å)
GLY11
3.716
GLN12
3.953
GLY13
3.668
LEU30
3.609
ASP32
2.542
GLY34
2.858
SER35
3.785
VAL69
3.734
PRO70
3.651
TYR71
3.168
THR72
3.022
GLN73
3.036
PHE108
3.758
ILE110
4.225
Residue
Distance (Å)
TRP115
4.176
ILE118
4.234
ILE126
3.933
ARG128
4.135
TYR198
4.010
ILE226
3.983
ASP228
2.534
GLY230
3.042
THR231
3.406
THR232
2.967
ASN233
4.483
ARG235
3.650
SER325
4.246
References  Top
REF 1 Structure-based design and synthesis of macrocyclic peptidomimetic beta-secretase (BACE-1) inhibitors. Bioorg Med Chem Lett. 2009 Mar 1;19(5):1361-5.
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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