Structure of PDB 8ju6 Chain B Binding Site BS01

Receptor Information
>8ju6 Chain B (length=616) Species: 9606 (Homo sapiens) [Search protein sequence] [Download receptor structure] [Download structure with residue number starting from 1] [View receptor structure]
VFNRPILFDIVSRGSTADLDGLLPFLLTHKKRLTDEEFREPSTGKTCLPK
ALLNLSNGRNDTIPVLLDIAERTGNMREFINSPFRDIYYRGQTALHIAIE
RRCKHYVELLVAQGADVHAQARGRFFQPKDEGGYFYFGELPLSLAACTNQ
PHIVNYLTENPHKKADMRRQDSRGNTVLHALVAIADNTRENTKFVTKMYD
LLLLKCARLFPDSNLEAVLNNDGLSPLMMAAKTGKIGIFQHIIRREVTDE
DTRHLSRKFKDWAYGPVYSSLYDLSSLDTCGEEASVLEILVYNSKIENRH
EMLAVEPINELLRDKWRKFGAVSFYINVVSYLCAMVIFTLTAYYQPLEGT
PPYPYRTTVDYLRLAGEVITLFTGVLFFFTNIKDLFMKKCPGVNSLFIDG
SFQLLYFIYSVLVIVSAALYLAGIEAYLAVMVFALVLGWMNALYFTRGLK
LTGTYSIMIQKILFKDLFRFLLVYLLFMIGYASALVSLLNPDSETFSTFL
LDLFKLTIGMGDLEMLSSTKYPVVFIILLVTYIILTFVLLLNMLIALMGE
TVGQVSKESKHIWKLQWATTILDIERSFPVFLRKAFRSGEMVTVGKSSDG
TPDRRWCFRVDEVNWS
Ligand information
Ligand IDXPW
InChIInChI=1S/C25H28N6O3/c1-23(2,33)20-11-28-21(12-27-20)31-15-25(34-22(31)32)8-4-7-24(3,13-25)14-30-16-29-18-6-5-17(10-26)9-19(18)30/h5-6,9,11-12,16,33H,4,7-8,13-15H2,1-3H3/t24-,25-/m0/s1
InChIKeyURCMKDJBULWNAI-DQEYMECFSA-N
SMILES
SoftwareSMILES
ACDLabs 12.01CC(C)(O)c1ncc(nc1)N1CC2(CCCC(C)(Cn3cnc4ccc(C#N)cc43)C2)OC1=O
OpenEye OEToolkits 2.0.7C[C@@]1(CCC[C@]2(C1)CN(C(=O)O2)c3cnc(cn3)C(C)(C)O)Cn4cnc5c4cc(cc5)C#N
CACTVS 3.385CC(C)(O)c1cnc(cn1)N2C[C@@]3(CCC[C@](C)(Cn4cnc5ccc(cc45)C#N)C3)OC2=O
OpenEye OEToolkits 2.0.7CC1(CCCC2(C1)CN(C(=O)O2)c3cnc(cn3)C(C)(C)O)Cn4cnc5c4cc(cc5)C#N
CACTVS 3.385CC(C)(O)c1cnc(cn1)N2C[C]3(CCC[C](C)(Cn4cnc5ccc(cc45)C#N)C3)OC2=O
FormulaC25 H28 N6 O3
Name1-({(5S,7S)-3-[5-(2-hydroxypropan-2-yl)pyrazin-2-yl]-7-methyl-2-oxo-1-oxa-3-azaspiro[4.5]decan-7-yl}methyl)-1H-benzimidazole-6-carbonitrile;
GSK2798745
ChEMBLCHEMBL4470585
DrugBankDB16033
ZINC
PDB chain8ju6 Chain B Residue 1201 [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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PDB8ju6 Structural Pharmacology of TRPV4 Antagonists.
Resolution3.45 Å
Binding residue
(original residue number in PDB)		N474 S477 Y478 F524 Y553 Y591 D743 I744
Binding residue
(residue number reindexed from 1)		N327 S330 Y331 F377 Y406 Y444 D573 I574
Annotation score1
Enzymatic activity
Enzyme Commision number ?
Gene Ontology
Molecular Function
GO:0003779 actin binding
GO:0005034 osmosensor activity
GO:0005080 protein kinase C binding
GO:0005216 monoatomic ion channel activity
GO:0005261 monoatomic cation channel activity
GO:0005262 calcium channel activity
GO:0005515 protein binding
GO:0005516 calmodulin binding
GO:0005524 ATP binding
GO:0008017 microtubule binding
GO:0008289 lipid binding
GO:0015275 stretch-activated, monoatomic cation-selective, calcium channel activity
GO:0019901 protein kinase binding
GO:0042169 SH2 domain binding
GO:0042802 identical protein binding
GO:0043014 alpha-tubulin binding
GO:0046872 metal ion binding
GO:0048487 beta-tubulin binding
GO:0051015 actin filament binding
Biological Process
GO:0000122 negative regulation of transcription by RNA polymerase II
GO:0001666 response to hypoxia
GO:0002024 diet induced thermogenesis
GO:0006091 generation of precursor metabolites and energy
GO:0006811 monoatomic ion transport
GO:0006816 calcium ion transport
GO:0006874 intracellular calcium ion homeostasis
GO:0006884 cell volume homeostasis
GO:0006970 response to osmotic stress
GO:0006971 hypotonic response
GO:0007015 actin filament organization
GO:0007043 cell-cell junction assembly
GO:0007204 positive regulation of cytosolic calcium ion concentration
GO:0007231 osmosensory signaling pathway
GO:0008218 bioluminescence
GO:0009612 response to mechanical stimulus
GO:0010628 positive regulation of gene expression
GO:0010759 positive regulation of macrophage chemotaxis
GO:0010977 negative regulation of neuron projection development
GO:0030036 actin cytoskeleton organization
GO:0030103 vasopressin secretion
GO:0031117 positive regulation of microtubule depolymerization
GO:0032755 positive regulation of interleukin-6 production
GO:0032868 response to insulin
GO:0034605 cellular response to heat
GO:0042538 hyperosmotic salinity response
GO:0042593 glucose homeostasis
GO:0043117 positive regulation of vascular permeability
GO:0043622 cortical microtubule organization
GO:0045989 positive regulation of striated muscle contraction
GO:0046330 positive regulation of JNK cascade
GO:0046785 microtubule polymerization
GO:0047484 regulation of response to osmotic stress
GO:0050729 positive regulation of inflammatory response
GO:0050891 multicellular organismal-level water homeostasis
GO:0055085 transmembrane transport
GO:0060351 cartilage development involved in endochondral bone morphogenesis
GO:0070374 positive regulation of ERK1 and ERK2 cascade
GO:0070509 calcium ion import
GO:0070588 calcium ion transmembrane transport
GO:0071470 cellular response to osmotic stress
GO:0071476 cellular hypotonic response
GO:0071477 cellular hypotonic salinity response
GO:0071639 positive regulation of monocyte chemotactic protein-1 production
GO:0071642 positive regulation of macrophage inflammatory protein 1 alpha production
GO:0071651 positive regulation of chemokine (C-C motif) ligand 5 production
GO:0097009 energy homeostasis
GO:0097497 blood vessel endothelial cell delamination
GO:1902656 calcium ion import into cytosol
GO:1903444 negative regulation of brown fat cell differentiation
GO:1903715 regulation of aerobic respiration
GO:2000340 positive regulation of chemokine (C-X-C motif) ligand 1 production
Cellular Component
GO:0005783 endoplasmic reticulum
GO:0005881 cytoplasmic microtubule
GO:0005886 plasma membrane
GO:0005912 adherens junction
GO:0005925 focal adhesion
GO:0005929 cilium
GO:0009986 cell surface
GO:0016020 membrane
GO:0016324 apical plasma membrane
GO:0030027 lamellipodium
GO:0030175 filopodium
GO:0030426 growth cone
GO:0030864 cortical actin cytoskeleton
GO:0032587 ruffle membrane
GO:0070161 anchoring junction

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Molecular Function
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Biological Process
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Cellular Component
External links
PDB RCSB:8ju6, PDBe:8ju6, PDBj:8ju6
PDBsum8ju6
PubMed38659239
UniProtQ9HBA0|TRPV4_HUMAN Transient receptor potential cation channel subfamily V member 4 (Gene Name=TRPV4)

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