Structure of PDB 5wg3 Chain A Binding Site BS01

Receptor Information
>5wg3 Chain A (length=618) Species: 9606 (Homo sapiens) [Search protein sequence] [Download receptor structure] [Download structure with residue number starting from 1] [View receptor structure]
KKILLPEPSIRSVMQKYLEDRGEVTFEKIFSQKLGYLLFRDFCLNHLEEA
RPLVEFYEEIKKYEKLETEEERVARSREIFDSYIMKELLACSHPFSKSAT
EHVQGHLGKKQVPPDLFQPYIEEICQNLRGDVFQKFIESDKFTRFCQWKN
VELNIHLTMNDFSVHRIIGRGGFGEVYGCRKADTGKMYAMKCLDKKRIKM
KQGETLALNERIMLSLVSTGDCPFIVCMSYAFHTPDKLSFILDLMNGGDL
HYHLSQHGVFSEADMRFYAAEIILGLEHMHNRFVVYRDLKPANILLDEHG
HVRISDLGLACDFSKKKPHASVGTHGYMAPEVLQKGVAYDSSADWFSLGC
MLFKLLRGHSPFRTKDKHEIDRMTLTVELPDSFSPELRSLLEGLLQRDVN
RRLGCLGRGAQEVKESPFFRSLDWQMVFLQKYPPPLIPPRGEVNAADAED
TKGIKLLDSDQELYRNFPLTISERWQQEVAETVFDTINAETDRLEARKKA
KNEDYALGKDCIMHGYMSKMGNPFLTQWQRRYFYLFPNRLEWRGEAPQSL
LTMEEIQSVEETQIKERKCLLLKIRGGKQFILQCDSDPELVQWKKELRDA
YREAQQLVQRVPKMKNKP
Ligand information
Ligand IDAFM
InChIInChI=1S/C24H25FN6O2/c25-22-3-1-15(10-21(22)24(32)27-13-18-5-8-28-30-18)20-6-7-26-11-17(20)14-33-19-2-4-23-16(9-19)12-29-31-23/h1-5,8-10,12,17,20,26H,6-7,11,13-14H2,(H,27,32)(H,28,30)(H,29,31)/t17-,20-/m0/s1
InChIKeyWQIAYJIICYWVKJ-PXNSSMCTSA-N
SMILES
SoftwareSMILES
OpenEye OEToolkits 2.0.6c1cc(c(cc1[C@@H]2CCNC[C@H]2COc3ccc4c(c3)cn[nH]4)C(=O)NCc5cc[nH]n5)F
OpenEye OEToolkits 2.0.6c1cc(c(cc1C2CCNCC2COc3ccc4c(c3)cn[nH]4)C(=O)NCc5cc[nH]n5)F
CACTVS 3.385Fc1ccc(cc1C(=O)NCc2cc[nH]n2)[C@@H]3CCNC[C@H]3COc4ccc5[nH]ncc5c4
ACDLabs 12.01c4(OCC1C(CCNC1)c2ccc(c(c2)C(NCc3nncc3)=O)F)cc5c(cc4)nnc5
CACTVS 3.385Fc1ccc(cc1C(=O)NCc2cc[nH]n2)[CH]3CCNC[CH]3COc4ccc5[nH]ncc5c4
FormulaC24 H25 F N6 O2
Name2-fluoro-5-[(3S,4R)-3-{[(1H-indazol-5-yl)oxy]methyl}piperidin-4-yl]-N-[(1H-pyrazol-3-yl)methyl]benzamide
ChEMBL
DrugBank
ZINC
PDB chain5wg3 Chain A Residue 701 [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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PDB5wg3 Structural Determinants Influencing the Potency and Selectivity of Indazole-Paroxetine Hybrid G Protein-Coupled Receptor Kinase 2 Inhibitors.
Resolution2.896 Å
Binding residue
(original residue number in PDB)		R199 G200 F202 G203 V205 K220 E239 M274 D278 A321 L324 D335
Binding residue
(residue number reindexed from 1)		R170 G171 F173 G174 V176 K191 E210 M245 D249 A292 L295 D306
Annotation score1
Binding affinityPDBbind-CN: -logKd/Ki=8.10,IC50=0.008uM
Enzymatic activity
Catalytic site (original residue number in PDB) D317 K319 N322 D335 K344 T353
Catalytic site (residue number reindexed from 1) D288 K290 N293 D306 K315 T324
Enzyme Commision number 2.7.11.15: [beta-adrenergic-receptor] kinase.
Gene Ontology
Molecular Function
GO:0001664 G protein-coupled receptor binding
GO:0004672 protein kinase activity
GO:0004674 protein serine/threonine kinase activity
GO:0004703 G protein-coupled receptor kinase activity
GO:0005515 protein binding
GO:0005524 ATP binding
GO:0031694 alpha-2A adrenergic receptor binding
GO:0031755 Edg-2 lysophosphatidic acid receptor binding
GO:0047696 beta-adrenergic receptor kinase activity
Biological Process
GO:0002026 regulation of the force of heart contraction
GO:0002029 desensitization of G protein-coupled receptor signaling pathway
GO:0003108 negative regulation of the force of heart contraction by chemical signal
GO:0006468 protein phosphorylation
GO:0007165 signal transduction
GO:0007186 G protein-coupled receptor signaling pathway
GO:0007213 G protein-coupled acetylcholine receptor signaling pathway
GO:0007217 tachykinin receptor signaling pathway
GO:0007507 heart development
GO:0016310 phosphorylation
GO:0018105 peptidyl-serine phosphorylation
GO:0019079 viral genome replication
GO:0031623 receptor internalization
GO:0033605 positive regulation of catecholamine secretion
GO:0045988 negative regulation of striated muscle contraction
GO:0046718 symbiont entry into host cell
GO:0060048 cardiac muscle contraction
GO:1901081 negative regulation of relaxation of smooth muscle
Cellular Component
GO:0005737 cytoplasm
GO:0005829 cytosol
GO:0005886 plasma membrane
GO:0005929 cilium
GO:0016020 membrane
GO:0032473 cytoplasmic side of mitochondrial outer membrane
GO:0042995 cell projection
GO:0045202 synapse
GO:0098793 presynapse
GO:0098794 postsynapse

View graph for
Molecular Function
View graph for
Biological Process
View graph for
Cellular Component
External links
PDB RCSB:5wg3, PDBe:5wg3, PDBj:5wg3
PDBsum5wg3
PubMed29070696
UniProtP25098|ARBK1_HUMAN Beta-adrenergic receptor kinase 1 (Gene Name=GRK2)

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