Target Binding Site Detail
| 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 | |||||
| Ligand General Information | Top | ||||
|---|---|---|---|---|---|
| Ligand Name | (4s)-4-[(1r)-1-Hydroxy-2-({1-[3-(1-Methylethyl)phenyl]cyclopropyl}amino)ethyl]-19-(Methoxymethyl)-11-Oxa-3,16-Diazatricyclo[15.3.1.1~6,10~]docosa-1(21),6(22),7,9,17,19-Hexaen-2-One | Ligand Info | |||
| Canonical SMILES | CC(C)C1=CC(=CC=C1)C2(CC2)NCC(C3CC4=CC(=CC=C4)OCCCCNC5=CC(=CC(=C5)C(=O)N3)COC)O | ||||
| InChI | 1S/C35H45N3O4/c1-24(2)27-9-7-10-29(20-27)35(12-13-35)37-22-33(39)32-19-25-8-6-11-31(18-25)42-15-5-4-14-36-30-17-26(23-41-3)16-28(21-30)34(40)38-32/h6-11,16-18,20-21,24,32-33,36-37,39H,4-5,12-15,19,22-23H2,1-3H3,(H,38,40)/t32-,33+/m0/s1 | ||||
| InChIKey | GCZHKZTYTMTFGU-JHOUSYSJSA-N | ||||
| PubChem Compound ID | 44631842 | ||||
| Drug Binding Sites of Target | Top | |||||
|---|---|---|---|---|---|---|
| PDB ID: 3K5C Human BACE-1 complex with NB-216 | ||||||
| Method | X-ray diffraction | Resolution | 2.12 Å | Mutation | No | [1] |
| PDB Sequence |
SFVEMVDNLR
7 GKSGQGYYVE17 MTVGSPPQTL27 NILVDTGSSN37 FAVGAAPHPF47 LHRYYQRQLS 57 STYRDLRKGV67 YVPYTQGKWE77 GELGTDLVSI87 PHGPNVTVRA97 NIAAITESDK 107 FFINGSNWEG117 ILGLAYAEIA127 RPDDSLEPFF137 DSLVKQTHVP147 NLFSLQLCGA 157 SVGGSMIIGG178 IDHSLYTGSL188 WYTPIRREWY198 YEVIIVRVEI208 NGQDLKMDCK 218 EYNYDKSIVD228 SGTTNLRLPK238 KVFEAAVKSI248 KAASSTEKFP258 DGFWLGEQLV 268 CWQAGTTPWN278 IFPVISLYLM288 GEVTNQSFRI298 TILPQQYLRP308 VEDVATSQDD 318 CYKFAISQSS328 TGTVMGAVIM338 EGFYVVFDRA348 RKRIGFAVSA358 CHVHDEFRTA 368 AVEGPFVTLD378 MEDCGYN
|
|||||
|
|
GLY11
3.608
GLN12
3.319
GLY13
3.596
LEU30
3.529
ASP32
2.625
GLY34
3.017
SER35
3.539
VAL69
3.452
PRO70
3.259
TYR71
3.386
THR72
3.188
GLN73
3.455
PHE108
3.387
|
|||||
| PDB ID: 5QD7 Crystal structure of BACE complex with BMC014 | ||||||
| Method | X-ray diffraction | Resolution | 2.12 Å | Mutation | No | [2] |
| PDB Sequence |
SFVEMVDNLR
7 GKSGQGYYVE17 MTVGSPPQTL27 NILVDTGSSN37 FAVGAAPHPF47 LHRYYQRQLS 57 STYRDLRKGV67 YVPYTQGKWE77 GELGTDLVSI87 PHGPNVTVRA97 NIAAITESDK 107 FFINGSNWEG117 ILGLAYAEIA127 RPDDSLEPFF137 DSLVKQTHVP147 NLFSLQLCGA 157 SVGGSMIIGG178 IDHSLYTGSL188 WYTPIRREWY198 YEVIIVRVEI208 NGQDLKMDCK 218 EYNYDKSIVD228 SGTTNLRLPK238 KVFEAAVKSI248 KAASSTEKFP258 DGFWLGEQLV 268 CWQAGTTPWN278 IFPVISLYLM288 GEVTNQSFRI298 TILPQQYLRP308 VEDVATSQDD 318 CYKFAISQSS328 TGTVMGAVIM338 EGFYVVFDRA348 RKRIGFAVSA358 CHVHDEFRTA 368 AVEGPFVTLD378 MEDCGYN
|
|||||
|
|
GLY11
3.598
GLN12
3.410
GLY13
3.673
LEU30
3.527
ASP32
2.549
GLY34
3.101
SER35
3.611
VAL69
3.513
PRO70
3.375
TYR71
3.319
THR72
3.290
GLN73
3.665
PHE108
3.347
|
|||||
| References | Top | ||||
|---|---|---|---|---|---|
| REF 1 | Macrocyclic BACE-1 inhibitors acutely reduce Abeta in brain after po application. Bioorg Med Chem Lett. 2010 Jan 15;20(2):603-7. | ||||
| 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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