Structure of PDB 7d8x Chain B Binding Site BS02

Receptor Information
>7d8x Chain B (length=307) Species: 9606 (Homo sapiens) [Search protein sequence] [Download receptor structure] [Download structure with residue number starting from 1] [View receptor structure]
KYGAKHVIMLFVPVTLCMVVVVATIKSVSFYTRKDGQLIYTPFTEDTETV
GQRALHSILNAAIMISVIVVMTILLVVLYKYRCYKVIHAWLIISSLLLLF
FFSFIYLGEVFKTYNVAVDYITVALLIWNFGVVGMISIHWKGPLRLQQAY
LIMISALMALVFIKYLPEWTAWLILAVISVYDLVAVLCPKGPLRMLVETA
QERNETLFPALIYSSTRGVKLGLGDFIFYSVLVGKASATASGDWNTTIAC
FVAILIGLCLTLLLLAIFKKALPALPISITFGLVFYFATDYLVQPFMDQL
AFHQFYI
Ligand information
Ligand IDFTO
InChIInChI=1S/C39H52N4O6/c1-26(2)21-33(37(47)41-32(35(40)45)24-29-19-13-8-14-20-29)42-36(46)30(22-27-15-9-6-10-16-27)25-34(44)31(23-28-17-11-7-12-18-28)43-38(48)49-39(3,4)5/h6-20,26,30-34,44H,21-25H2,1-5H3,(H2,40,45)(H,41,47)(H,42,46)(H,43,48)/t30-,31+,32+,33+,34-/m1/s1
InChIKeyMURCDOXDAHPNRQ-ZJKZPDEISA-N
SMILES
SoftwareSMILES
OpenEye OEToolkits 2.0.7CC(C)CC(C(=O)NC(Cc1ccccc1)C(=O)N)NC(=O)C(Cc2ccccc2)CC(C(Cc3ccccc3)NC(=O)OC(C)(C)C)O
CACTVS 3.385CC(C)C[C@H](NC(=O)[C@@H](C[C@@H](O)[C@H](Cc1ccccc1)NC(=O)OC(C)(C)C)Cc2ccccc2)C(=O)N[C@@H](Cc3ccccc3)C(N)=O
OpenEye OEToolkits 2.0.7CC(C)C[C@@H](C(=O)N[C@@H](Cc1ccccc1)C(=O)N)NC(=O)[C@H](Cc2ccccc2)C[C@H]([C@H](Cc3ccccc3)NC(=O)OC(C)(C)C)O
CACTVS 3.385CC(C)C[CH](NC(=O)[CH](C[CH](O)[CH](Cc1ccccc1)NC(=O)OC(C)(C)C)Cc2ccccc2)C(=O)N[CH](Cc3ccccc3)C(N)=O
FormulaC39 H52 N4 O6
Name~{tert}-butyl ~{N}-[(2~{S},3~{R},5~{R})-6-[[(2~{S})-1-[[(2~{S})-1-azanyl-1-oxidanylidene-3-phenyl-propan-2-yl]amino]-4-methyl-1-oxidanylidene-pentan-2-yl]amino]-3-oxidanyl-6-oxidanylidene-1-phenyl-5-(phenylmethyl)hexan-2-yl]carbamate;
L-685,458
ChEMBLCHEMBL302004
DrugBank
ZINCZINC000026179223
PDB chain7d8x Chain B Residue 504 [Download ligand structure] [Download structure with residue number starting from 1] [View ligand structure]
Receptor-Ligand Complex Structure
Global viewLocal viewStructure summary

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PDB7d8x Structural basis of gamma-secretase inhibition and modulation by small molecule drugs.
Resolution2.6 Å
Binding residue
(original residue number in PDB)		D257 L268 V272 L286 K380 G384 D385 L432
Binding residue
(residue number reindexed from 1)		D182 L193 V197 L211 K220 G224 D225 L272
Annotation score1
Binding affinityBindingDB: IC50=36nM
Enzymatic activity
Enzyme Commision number 3.4.23.-
Gene Ontology
Molecular Function
GO:0004175 endopeptidase activity
GO:0004190 aspartic-type endopeptidase activity
GO:0005262 calcium channel activity
GO:0005515 protein binding
GO:0008013 beta-catenin binding
GO:0008233 peptidase activity
GO:0030165 PDZ domain binding
GO:0042500 aspartic endopeptidase activity, intramembrane cleaving
GO:0045296 cadherin binding
GO:0051117 ATPase binding
GO:0070851 growth factor receptor binding
Biological Process
GO:0000045 autophagosome assembly
GO:0000122 negative regulation of transcription by RNA polymerase II
GO:0001568 blood vessel development
GO:0001708 cell fate specification
GO:0001756 somitogenesis
GO:0001764 neuron migration
GO:0001921 positive regulation of receptor recycling
GO:0001947 heart looping
GO:0002038 positive regulation of L-glutamate import across plasma membrane
GO:0002244 hematopoietic progenitor cell differentiation
GO:0002265 astrocyte activation involved in immune response
GO:0002286 T cell activation involved in immune response
GO:0002573 myeloid leukocyte differentiation
GO:0003407 neural retina development
GO:0006486 protein glycosylation
GO:0006508 proteolysis
GO:0006509 membrane protein ectodomain proteolysis
GO:0006839 mitochondrial transport
GO:0006874 intracellular calcium ion homeostasis
GO:0006914 autophagy
GO:0006915 apoptotic process
GO:0006974 DNA damage response
GO:0006979 response to oxidative stress
GO:0007155 cell adhesion
GO:0007175 negative regulation of epidermal growth factor-activated receptor activity
GO:0007219 Notch signaling pathway
GO:0007220 Notch receptor processing
GO:0007420 brain development
GO:0007507 heart development
GO:0007611 learning or memory
GO:0007613 memory
GO:0009791 post-embryonic development
GO:0010467 gene expression
GO:0010468 regulation of gene expression
GO:0010628 positive regulation of gene expression
GO:0010629 negative regulation of gene expression
GO:0010975 regulation of neuron projection development
GO:0015031 protein transport
GO:0015871 choline transport
GO:0016080 synaptic vesicle targeting
GO:0016485 protein processing
GO:0021549 cerebellum development
GO:0021795 cerebral cortex cell migration
GO:0021870 Cajal-Retzius cell differentiation
GO:0021904 dorsal/ventral neural tube patterning
GO:0021987 cerebral cortex development
GO:0022008 neurogenesis
GO:0030182 neuron differentiation
GO:0030326 embryonic limb morphogenesis
GO:0030900 forebrain development
GO:0032436 positive regulation of proteasomal ubiquitin-dependent protein catabolic process
GO:0032469 endoplasmic reticulum calcium ion homeostasis
GO:0032760 positive regulation of tumor necrosis factor production
GO:0034205 amyloid-beta formation
GO:0035282 segmentation
GO:0035556 intracellular signal transduction
GO:0040011 locomotion
GO:0042307 positive regulation of protein import into nucleus
GO:0042325 regulation of phosphorylation
GO:0042982 amyloid precursor protein metabolic process
GO:0042987 amyloid precursor protein catabolic process
GO:0043011 myeloid dendritic cell differentiation
GO:0043065 positive regulation of apoptotic process
GO:0043066 negative regulation of apoptotic process
GO:0043524 negative regulation of neuron apoptotic process
GO:0043589 skin morphogenesis
GO:0045821 positive regulation of glycolytic process
GO:0045893 positive regulation of DNA-templated transcription
GO:0048143 astrocyte activation
GO:0048167 regulation of synaptic plasticity
GO:0048538 thymus development
GO:0048666 neuron development
GO:0048705 skeletal system morphogenesis
GO:0048854 brain morphogenesis
GO:0050435 amyloid-beta metabolic process
GO:0050673 epithelial cell proliferation
GO:0050771 negative regulation of axonogenesis
GO:0050808 synapse organization
GO:0050820 positive regulation of coagulation
GO:0050852 T cell receptor signaling pathway
GO:0051208 sequestering of calcium ion
GO:0051402 neuron apoptotic process
GO:0051444 negative regulation of ubiquitin-protein transferase activity
GO:0051563 smooth endoplasmic reticulum calcium ion homeostasis
GO:0051604 protein maturation
GO:0051966 regulation of synaptic transmission, glutamatergic
GO:0055074 calcium ion homeostasis
GO:0060075 regulation of resting membrane potential
GO:0060828 regulation of canonical Wnt signaling pathway
GO:0060999 positive regulation of dendritic spine development
GO:0070050 neuron cellular homeostasis
GO:0070588 calcium ion transmembrane transport
GO:0097190 apoptotic signaling pathway
GO:0098609 cell-cell adhesion
GO:0098693 regulation of synaptic vesicle cycle
GO:0098712 L-glutamate import across plasma membrane
GO:0099175 regulation of postsynapse organization
GO:0140249 protein catabolic process at postsynapse
GO:1904646 cellular response to amyloid-beta
GO:1904797 negative regulation of core promoter binding
GO:1905598 negative regulation of low-density lipoprotein receptor activity
GO:1905908 positive regulation of amyloid fibril formation
GO:1990535 neuron projection maintenance
GO:2000059 negative regulation of ubiquitin-dependent protein catabolic process
GO:2001234 negative regulation of apoptotic signaling pathway
Cellular Component
GO:0000139 Golgi membrane
GO:0000776 kinetochore
GO:0005634 nucleus
GO:0005640 nuclear outer membrane
GO:0005654 nucleoplasm
GO:0005737 cytoplasm
GO:0005739 mitochondrion
GO:0005743 mitochondrial inner membrane
GO:0005765 lysosomal membrane
GO:0005768 endosome
GO:0005769 early endosome
GO:0005783 endoplasmic reticulum
GO:0005789 endoplasmic reticulum membrane
GO:0005790 smooth endoplasmic reticulum
GO:0005791 rough endoplasmic reticulum
GO:0005794 Golgi apparatus
GO:0005813 centrosome
GO:0005886 plasma membrane
GO:0005938 cell cortex
GO:0008021 synaptic vesicle
GO:0009986 cell surface
GO:0016020 membrane
GO:0016235 aggresome
GO:0030054 cell junction
GO:0030424 axon
GO:0030425 dendrite
GO:0030426 growth cone
GO:0031410 cytoplasmic vesicle
GO:0031594 neuromuscular junction
GO:0031901 early endosome membrane
GO:0031965 nuclear membrane
GO:0032991 protein-containing complex
GO:0035253 ciliary rootlet
GO:0035577 azurophil granule membrane
GO:0042383 sarcolemma
GO:0042734 presynaptic membrane
GO:0042995 cell projection
GO:0043005 neuron projection
GO:0043025 neuronal cell body
GO:0043198 dendritic shaft
GO:0045121 membrane raft
GO:0045202 synapse
GO:0070765 gamma-secretase complex
GO:0097060 synaptic membrane
GO:0098794 postsynapse
GO:0098978 glutamatergic synapse

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Molecular Function
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Biological Process
View graph for
Cellular Component
External links
PDB RCSB:7d8x, PDBe:7d8x, PDBj:7d8x
PDBsum7d8x
PubMed33373587
UniProtP49768|PSN1_HUMAN Presenilin-1 (Gene Name=PSEN1)

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