Structure of PDB 6c0u Chain A Binding Site BS01

Receptor Information
>6c0u Chain A (length=340) Species: 9606 (Homo sapiens) [Search protein sequence] [Download receptor structure] [Download structure with residue number starting from 1] [View receptor structure]
EQESVKEFLAKAKEDFLKKWESPAQNTAHLDQFERIKTLGTGSFGRVMLV
KHKETGNHYAMKILDKQKVVKLKQIEHTLNEKRILQAVNFPFLVKLEFSF
KDNSNLYMVMEYVPGGEMFSHLRRIGRFSEPHARFYAAQIVLTFEYLHSL
DLIYRDLKPENLLIDQQGYIQVTDFGFAKRVKGRTWTLCGTPEYLAPEII
LSKGYNKAVDWWALGVLIYEMAAGYPPFFADQPIQIYEKIVSGKVRFPSH
FSSDLKDLLRNLLQVDLTKRFGNLKNGVNDIKNHKWFATTDWIAIYQRKV
EAPFIPKFKGPGDTSNFDDYEEEEIRVSINEKCGKEFSEF
Ligand information
Ligand IDEE4
InChIInChI=1S/C30H30FN5O5/c1-3-12-41-24-10-11-25(40-2)27(31)26(24)28(37)17-4-6-18(7-5-17)29(38)34-22-15-32-16-23(22)35-30(39)19-8-9-21-20(13-19)14-33-36-21/h4-11,13-14,22-23,32H,3,12,15-16H2,1-2H3,(H,33,36)(H,34,38)(H,35,39)/t22-,23-/m1/s1
InChIKeyAYXNTJKOINXKAJ-DHIUTWEWSA-N
SMILES
SoftwareSMILES
OpenEye OEToolkits 2.0.6CCCOc1ccc(c(c1C(=O)c2ccc(cc2)C(=O)N[C@@H]3CNC[C@H]3NC(=O)c4ccc5c(c4)cn[nH]5)F)OC
CACTVS 3.385CCCOc1ccc(OC)c(F)c1C(=O)c2ccc(cc2)C(=O)N[C@@H]3CNC[C@H]3NC(=O)c4ccc5[nH]ncc5c4
ACDLabs 12.01c5c(C(c1c(OCCC)ccc(c1F)OC)=O)ccc(C(=O)NC2C(CNC2)NC(=O)c3cc4c(cc3)nnc4)c5
CACTVS 3.385CCCOc1ccc(OC)c(F)c1C(=O)c2ccc(cc2)C(=O)N[CH]3CNC[CH]3NC(=O)c4ccc5[nH]ncc5c4
OpenEye OEToolkits 2.0.6CCCOc1ccc(c(c1C(=O)c2ccc(cc2)C(=O)NC3CNCC3NC(=O)c4ccc5c(c4)cn[nH]5)F)OC
FormulaC30 H30 F N5 O5
NameN-[(3R,4R)-4-{[4-(2-fluoro-3-methoxy-6-propoxybenzene-1-carbonyl)benzene-1-carbonyl]amino}pyrrolidin-3-yl]-1H-indazole-5-carboxamide
ChEMBL
DrugBank
ZINC
PDB chain6c0u Chain A Residue 400 [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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PDB6c0u Structural basis for selective inhibition of human PKG I alpha by the balanol-like compound N46.
Resolution2.65 Å
Binding residue
(original residue number in PDB)		G50 T51 G52 S53 F54 G55 V57 A70 L74 T88 M120 E121 Y122 V123 E127 E170 L173 T183
Binding residue
(residue number reindexed from 1)		G40 T41 G42 S43 F44 G45 V47 A60 L64 T78 M110 E111 Y112 V113 E117 E160 L163 T173
Annotation score1
Binding affinityPDBbind-CN: -logKd/Ki=5.99,IC50=1030nM
Enzymatic activity
Catalytic site (original residue number in PDB) D166 K168 N171 D184 T201
Catalytic site (residue number reindexed from 1) D156 K158 N161 D174 T191
Enzyme Commision number 2.7.11.11: cAMP-dependent protein kinase.
Gene Ontology
Molecular Function
GO:0000287 magnesium ion binding
GO:0004672 protein kinase activity
GO:0004674 protein serine/threonine kinase activity
GO:0004679 AMP-activated protein kinase activity
GO:0004691 cAMP-dependent protein kinase activity
GO:0004712 protein serine/threonine/tyrosine kinase activity
GO:0005515 protein binding
GO:0005524 ATP binding
GO:0019901 protein kinase binding
GO:0019904 protein domain specific binding
GO:0030145 manganese ion binding
GO:0031625 ubiquitin protein ligase binding
GO:0034237 protein kinase A regulatory subunit binding
GO:0099103 channel activator activity
GO:0106310 protein serine kinase activity
Biological Process
GO:0001707 mesoderm formation
GO:0001843 neural tube closure
GO:0002027 regulation of heart rate
GO:0003091 renal water homeostasis
GO:0006397 mRNA processing
GO:0006468 protein phosphorylation
GO:0006611 protein export from nucleus
GO:0007189 adenylate cyclase-activating G protein-coupled receptor signaling pathway
GO:0007193 adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway
GO:0010737 protein kinase A signaling
GO:0010881 regulation of cardiac muscle contraction by regulation of the release of sequestered calcium ion
GO:0016241 regulation of macroautophagy
GO:0016310 phosphorylation
GO:0018105 peptidyl-serine phosphorylation
GO:0019221 cytokine-mediated signaling pathway
GO:0032024 positive regulation of insulin secretion
GO:0032703 negative regulation of interleukin-2 production
GO:0034380 high-density lipoprotein particle assembly
GO:0034605 cellular response to heat
GO:0035694 mitochondrial protein catabolic process
GO:0045542 positive regulation of cholesterol biosynthetic process
GO:0045667 regulation of osteoblast differentiation
GO:0045722 positive regulation of gluconeogenesis
GO:0045879 negative regulation of smoothened signaling pathway
GO:0046827 positive regulation of protein export from nucleus
GO:0048240 sperm capacitation
GO:0050804 modulation of chemical synaptic transmission
GO:0050850 positive regulation of calcium-mediated signaling
GO:0051726 regulation of cell cycle
GO:0055117 regulation of cardiac muscle contraction
GO:0061136 regulation of proteasomal protein catabolic process
GO:0070417 cellular response to cold
GO:0070613 regulation of protein processing
GO:0071333 cellular response to glucose stimulus
GO:0071374 cellular response to parathyroid hormone stimulus
GO:0071377 cellular response to glucagon stimulus
GO:0071872 cellular response to epinephrine stimulus
GO:0086064 cell communication by electrical coupling involved in cardiac conduction
GO:0099170 postsynaptic modulation of chemical synaptic transmission
GO:1903779 regulation of cardiac conduction
GO:1904262 negative regulation of TORC1 signaling
GO:1904539 negative regulation of glycolytic process through fructose-6-phosphate
GO:1990044 protein localization to lipid droplet
GO:2000810 regulation of bicellular tight junction assembly
Cellular Component
GO:0001669 acrosomal vesicle
GO:0005634 nucleus
GO:0005654 nucleoplasm
GO:0005737 cytoplasm
GO:0005739 mitochondrion
GO:0005759 mitochondrial matrix
GO:0005813 centrosome
GO:0005829 cytosol
GO:0005886 plasma membrane
GO:0005930 axoneme
GO:0005952 cAMP-dependent protein kinase complex
GO:0016607 nuclear speck
GO:0031410 cytoplasmic vesicle
GO:0031514 motile cilium
GO:0031594 neuromuscular junction
GO:0034704 calcium channel complex
GO:0036126 sperm flagellum
GO:0044853 plasma membrane raft
GO:0048471 perinuclear region of cytoplasm
GO:0070062 extracellular exosome
GO:0097546 ciliary base
GO:0098794 postsynapse
GO:0098978 glutamatergic synapse

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Molecular Function
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Biological Process
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Cellular Component
External links
PDB RCSB:6c0u, PDBe:6c0u, PDBj:6c0u
PDBsum6c0u
PubMed29769318
UniProtP17612|KAPCA_HUMAN cAMP-dependent protein kinase catalytic subunit alpha (Gene Name=PRKACA)

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