Structure of PDB 5htz Chain A Binding Site BS01

Receptor Information
>5htz Chain A (length=388) Species: 9606 (Homo sapiens) [Search protein sequence] [Download receptor structure] [Download structure with residue number starting from 1] [View receptor structure]
RGSFVEMVDNLRGKSGQGYYVEMTVGSPPQTLNILVDTGSSNFAVGAAPH
PFLHRYYQRQLSSTYRDLRKGVYVPYTQGKWEGELGTDLVSIPHGPNVTV
RANIAAITESDKFFINGSNWEGILGLAYAEIARPDDSLEPFFDSLVKQTH
VPNLFSLQLCGAGFPLNQSEVLASVGGSMIIGGIDHSLYTGSLWYTPIRR
EWYYEVIIVRVEINGQDLKMDCKEYNYDKSIVDSGTTNLRLPKKVFEAAV
KSIKAASSTEKFPDGFWLGEQLVCWQAGTTPWNIFPVISLYLMGEVTNQS
FRITILPQQYLRPVEDSQDDCYKFAISQSSTGTVMGAVIMEGFYVVFDRA
RKRIGFAVSACHVHDEFRTAAVEGPFVTLDMEDCGYNI
Ligand information
Ligand ID66J
InChIInChI=1S/C17H17ClN4O2S2/c1-4-5-11-6-12(9-20-8-11)14-7-13(18)15(25-14)17(2)10-26(23,24)22(3)16(19)21-17/h6-9H,10H2,1-3H3,(H2,19,21)/t17-/m0/s1
InChIKeyVKVMIZCLMUKTTA-KRWDZBQOSA-N
SMILES
SoftwareSMILES
CACTVS 3.385CC#Cc1cncc(c1)c2sc(c(Cl)c2)[C]3(C)C[S](=O)(=O)N(C)C(=N)N3
CACTVS 3.385CC#Cc1cncc(c1)c2sc(c(Cl)c2)[C@]3(C)C[S](=O)(=O)N(C)C(=N)N3
ACDLabs 12.01c3(c2cc(c(C1(C)CS(N(\C(=N)N1)C)(=O)=O)s2)Cl)cc(C#CC)cnc3
OpenEye OEToolkits 2.0.4CC#Cc1cc(cnc1)c2cc(c(s2)C3(CS(=O)(=O)N(C(=N)N3)C)C)Cl
OpenEye OEToolkits 2.0.4[H]/N=C/1\N[C@](CS(=O)(=O)N1C)(C)c2c(cc(s2)c3cc(cnc3)C#CC)Cl
FormulaC17 H17 Cl N4 O2 S2
Name(3E,5S)-5-{3-chloro-5-[5-(prop-1-yn-1-yl)pyridin-3-yl]thiophen-2-yl}-2,5-dimethyl-1,2,4-thiadiazinan-3-imine 1,1-dioxide
ChEMBLCHEMBL3259832
DrugBank
ZINCZINC000144605596
PDB chain5htz Chain A Residue 501 [Download ligand structure] [Download structure with residue number starting from 1] [View ligand structure]
Receptor-Ligand Complex Structure
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PDB5htz Discovery of the 3-Imino-1,2,4-thiadiazinane 1,1-Dioxide Derivative Verubecestat (MK-8931)-A beta-Site Amyloid Precursor Protein Cleaving Enzyme 1 Inhibitor for the Treatment of Alzheimer's Disease.
Resolution1.95 Å
Binding residue
(original residue number in PDB)		S71 Q73 G74 L91 D93 Y132 Q134 F169 W176 D289 S290 G291 T292
Binding residue
(residue number reindexed from 1)		S15 Q17 G18 L35 D37 Y76 Q78 F113 W120 D233 S234 G235 T236
Annotation score1
Binding affinityMOAD: Ki=2.4nM
PDBbind-CN: -logKd/Ki=8.62,Ki=2.4nM
BindingDB: Ki=2.387nM
Enzymatic activity
Catalytic site (original residue number in PDB) D93 S96 N98 A100 Y132 D289 T292
Catalytic site (residue number reindexed from 1) D37 S40 N42 A44 Y76 D233 T236
Enzyme Commision number 3.4.23.46: memapsin 2.
Gene Ontology
Molecular Function
GO:0004190 aspartic-type endopeptidase activity
Biological Process
GO:0006508 proteolysis
Cellular Component
GO:0016020 membrane

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Molecular Function
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Biological Process
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Cellular Component
External links
PDB RCSB:5htz, PDBe:5htz, PDBj:5htz
PDBsum5htz
PubMed27933948
UniProtP56817|BACE1_HUMAN Beta-secretase 1 (Gene Name=BACE1)

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