Structure of PDB 6u2p Chain B Binding Site BS01

Receptor Information
>6u2p Chain B (length=481) Species: 9606 (Homo sapiens) [Search protein sequence] [Download receptor structure] [Download structure with residue number starting from 1] [View receptor structure]
SIPWNLERITPPRYRLVEVYLLDTSIQSDHREIEGRVMVTDFENVPEEDA
SKCDSHGTHLAGVVSGRDAGVAKGASMRSLRVLNCQGKGTVSGTLIGLEF
IRKSQLVQPVGPLVVLLPLAGGYSRVLNAACQRLARAGVVLVTAAGNFRD
DACLYSPASAPEVITVGATNAQDQPVTLGTLGTNFGRCVDLFAPGEDIIG
ASSDCSTCFVSQSGTSQAAAHVAGIAAMMLSAEPELTLAELRQRLIHFSA
KDVINEAWFPEDQRVLTPNLVAALPPSTHGWQLFCRTVWSAHSGPTRMAT
AIARCAPDEELLSCSSFSRSGKRRGERMEAQGGKLVCRAHNAFGGEGVYA
IARCCLLPANCSVHTAPPAASMGTRVHCHQQGHVLTGCSSHWEVEDLQPN
QCVGHREASIHASCCHAPGLECKVKEHGIPQEQVTVACEEGWTLTGCSAL
PSHVLGAYAVDNTCVVRSRAVTAVAICCRSR
Ligand information
Ligand IDPUV
InChIInChI=1S/C23H22FN3O5S/c1-23(12-20(28)27-22-25-7-8-33-22)16-11-19(18(31-2)9-13(16)5-6-26-23)32-14-3-4-15(21(29)30)17(24)10-14/h3-4,7-11,26H,5-6,12H2,1-2H3,(H,29,30)(H,25,27,28)/t23-/m1/s1
InChIKeyPZYUALDJGJBZEM-HSZRJFAPSA-N
SMILES
SoftwareSMILES
ACDLabs 12.01c1cc(cc(c1C(O)=O)F)Oc2cc3c(cc2OC)CCNC3(C)CC(Nc4nccs4)=O
CACTVS 3.385COc1cc2CCN[C](C)(CC(=O)Nc3sccn3)c2cc1Oc4ccc(C(O)=O)c(F)c4
CACTVS 3.385COc1cc2CCN[C@](C)(CC(=O)Nc3sccn3)c2cc1Oc4ccc(C(O)=O)c(F)c4
OpenEye OEToolkits 2.0.7CC1(c2cc(c(cc2CCN1)OC)Oc3ccc(c(c3)F)C(=O)O)CC(=O)Nc4nccs4
OpenEye OEToolkits 2.0.7C[C@]1(c2cc(c(cc2CCN1)OC)Oc3ccc(c(c3)F)C(=O)O)CC(=O)Nc4nccs4
FormulaC23 H22 F N3 O5 S
Name2-fluoro-4-{[(1R)-6-methoxy-1-methyl-1-{2-oxo-2-[(1,3-thiazol-2-yl)amino]ethyl}-1,2,3,4-tetrahydroisoquinolin-7-yl]oxy}benzoic acid
ChEMBL
DrugBank
ZINC
PDB chain6u2p Chain B Residue 804 [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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PDB6u2p From Screening to Targeted Degradation: Strategies for the Discovery and Optimization of Small Molecule Ligands for PCSK9.
Resolution2.04 Å
Binding residue
(original residue number in PDB)		S329 A330 P331 R357 C358 D360 R412 R458 V460 R476 A478
Binding residue
(residue number reindexed from 1)		S159 A160 P161 R187 C188 D190 R242 R286 V288 R304 A306
Annotation score1
Enzymatic activity
Enzyme Commision number 3.4.21.-
Gene Ontology
Molecular Function
GO:0003723 RNA binding
GO:0004252 serine-type endopeptidase activity
GO:0005515 protein binding
GO:0008236 serine-type peptidase activity
GO:0019871 sodium channel inhibitor activity
GO:0030169 low-density lipoprotein particle binding
GO:0030547 signaling receptor inhibitor activity
GO:0034185 apolipoprotein binding
GO:0034189 very-low-density lipoprotein particle binding
GO:0034190 apolipoprotein receptor binding
GO:0050750 low-density lipoprotein particle receptor binding
GO:0070326 very-low-density lipoprotein particle receptor binding
Biological Process
GO:0001822 kidney development
GO:0001889 liver development
GO:0001920 negative regulation of receptor recycling
GO:0002091 negative regulation of receptor internalization
GO:0002092 positive regulation of receptor internalization
GO:0006508 proteolysis
GO:0006641 triglyceride metabolic process
GO:0006644 phospholipid metabolic process
GO:0006915 apoptotic process
GO:0007041 lysosomal transport
GO:0008203 cholesterol metabolic process
GO:0009267 cellular response to starvation
GO:0010469 regulation of signaling receptor activity
GO:0010989 negative regulation of low-density lipoprotein particle clearance
GO:0016485 protein processing
GO:0016540 protein autoprocessing
GO:0022008 neurogenesis
GO:0030182 neuron differentiation
GO:0032799 low-density lipoprotein receptor particle metabolic process
GO:0032802 low-density lipoprotein particle receptor catabolic process
GO:0032803 regulation of low-density lipoprotein particle receptor catabolic process
GO:0032805 positive regulation of low-density lipoprotein particle receptor catabolic process
GO:0032869 cellular response to insulin stimulus
GO:0042157 lipoprotein metabolic process
GO:0042632 cholesterol homeostasis
GO:0043523 regulation of neuron apoptotic process
GO:0043525 positive regulation of neuron apoptotic process
GO:1905596 negative regulation of low-density lipoprotein particle receptor binding
GO:1905598 negative regulation of low-density lipoprotein receptor activity
GO:1905601 negative regulation of receptor-mediated endocytosis involved in cholesterol transport
GO:2000650 negative regulation of sodium ion transmembrane transporter activity
Cellular Component
GO:0005576 extracellular region
GO:0005615 extracellular space
GO:0005737 cytoplasm
GO:0005764 lysosome
GO:0005765 lysosomal membrane
GO:0005768 endosome
GO:0005769 early endosome
GO:0005770 late endosome
GO:0005783 endoplasmic reticulum
GO:0005788 endoplasmic reticulum lumen
GO:0005794 Golgi apparatus
GO:0005886 plasma membrane
GO:0009986 cell surface
GO:0030134 COPII-coated ER to Golgi transport vesicle
GO:0031232 extrinsic component of external side of plasma membrane
GO:0036020 endolysosome membrane
GO:0048471 perinuclear region of cytoplasm
GO:1990666 PCSK9-LDLR complex
GO:1990667 PCSK9-AnxA2 complex

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Molecular Function
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Biological Process
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Cellular Component
External links
PDB RCSB:6u2p, PDBe:6u2p, PDBj:6u2p
PDBsum6u2p
PubMed31653597
UniProtQ8NBP7|PCSK9_HUMAN Proprotein convertase subtilisin/kexin type 9 (Gene Name=PCSK9)

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