Structure of PDB 5ukm Chain A Binding Site BS01

Receptor Information
>5ukm Chain A (length=621) Species: 9913 (Bos taurus) [Search protein sequence] [Download receptor structure] [Download structure with residue number starting from 1] [View receptor structure]
KILLPEPSIRSVMQKYLEDRGEVTFEKIFSQKLGYLLFRDFCLKHLEEAK
PLVEFYEEIKKYEKLETEEERLVCSREIFDTYIMKELLACSHPFSKSAIE
HVQGHLVKKQVPPDLFQPYIEEICQNLRGDVFQKFIESDKFTRFCQWKNV
ELNIHLTMNDFSVHRIIGRGGFGEVYGCRKADTGKMYAMKCLDKKRIKMK
QGETLALNERIMLSLVSTGDCPFIVCMSYAFHTPDKLSFILDLMNGGDLH
YHLSQHGVFSEADMRFYAAEIILGLEHMHNRFVVYRDLKPANILLDEHGH
VRISDLGLACDFSKKKPHASVGTHGYMAPEVLQKGVAYDSSADWFSLGCM
LFKLLRGHSPFRQHKTKDKHEIDRMTLTMAVELPDSFSPELRSLLEGLLQ
RDVNRRLGCLGRGAQEVKESPFFRSLDWQMVFLQKYPPPLIPPRGEVNAA
DAFDIKLLDSDQELYRNFPLTISERWQQEVAETVFDTINAETDRLEARKK
TKNKQLGHEEDYALGKDCIMHGYMSKMWQRRYFYLFPNRLEWRGEGEAPQ
SLLTMEEIQSVEETQIKERKCLLLKIRGGKQFVLQCDSDPELVQWKKELR
DAYREAQQLVQRVPKMKNKPR
Ligand information
Ligand IDT0E
InChIInChI=1S/C24H25FN4O4/c25-21-3-1-15(9-20(21)24(30)27-12-17-5-8-28-29-17)19-6-7-26-11-16(19)13-31-18-2-4-22-23(10-18)33-14-32-22/h1-5,8-10,16,19,26H,6-7,11-14H2,(H,27,30)(H,28,29)/t16-,19-/m0/s1
InChIKeyXQUKEAYUAYTIBV-LPHOPBHVSA-N
SMILES
SoftwareSMILES
OpenEye OEToolkits 2.0.6c1cc(c(cc1C2CCNCC2COc3ccc4c(c3)OCO4)C(=O)NCc5ccn[nH]5)F
CACTVS 3.385Fc1ccc(cc1C(=O)NCc2[nH]ncc2)[CH]3CCNC[CH]3COc4ccc5OCOc5c4
OpenEye OEToolkits 2.0.6c1cc(c(cc1[C@@H]2CCNC[C@H]2COc3ccc4c(c3)OCO4)C(=O)NCc5ccn[nH]5)F
ACDLabs 12.01O=C(NCc1ccnn1)c2c(F)ccc(c2)C5C(COc4cc3OCOc3cc4)CNCC5
CACTVS 3.385Fc1ccc(cc1C(=O)NCc2[nH]ncc2)[C@@H]3CCNC[C@H]3COc4ccc5OCOc5c4
FormulaC24 H25 F N4 O4
Name5-[(3S,4R)-3-{[(2H-1,3-benzodioxol-5-yl)oxy]methyl}piperidin-4-yl]-2-fluoro-N-[(1H-pyrazol-5-yl)methyl]benzamide
ChEMBLCHEMBL4090144
DrugBank
ZINC
PDB chain5ukm 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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PDB5ukm Structure-Based Design of Highly Selective and Potent G Protein-Coupled Receptor Kinase 2 Inhibitors Based on Paroxetine.
Resolution3.03 Å
Binding residue
(original residue number in PDB)		I197 R199 G200 F202 G203 E204 V205 A218 E239 V255 M274 A321 L324 S334 D335
Binding residue
(residue number reindexed from 1)		I167 R169 G170 F172 G173 E174 V175 A188 E209 V225 M244 A291 L294 S304 D305
Annotation score1
Binding affinityPDBbind-CN: -logKd/Ki=7.52,IC50=0.03uM
BindingDB: IC50=30nM
Enzymatic activity
Catalytic site (original residue number in PDB) D317 K319 N322 D335 K344 T353
Catalytic site (residue number reindexed from 1) D287 K289 N292 D305 K314 T323
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:0002031 G protein-coupled receptor internalization
GO:0003108 negative regulation of the force of heart contraction by chemical signal
GO:0006468 protein phosphorylation
GO:0006886 intracellular protein transport
GO:0007165 signal transduction
GO:0007186 G protein-coupled receptor signaling pathway
GO:0007213 G protein-coupled acetylcholine receptor signaling pathway
GO:0009966 regulation of signal transduction
GO:0016310 phosphorylation
GO:0018105 peptidyl-serine phosphorylation
GO:0045880 positive regulation of smoothened signaling pathway
GO:0045988 negative regulation of striated muscle contraction
GO:0060048 cardiac muscle contraction
GO:1901081 negative regulation of relaxation of smooth muscle
GO:1903566 positive regulation of protein localization to cilium
Cellular Component
GO:0005737 cytoplasm
GO:0005829 cytosol
GO:0005886 plasma membrane
GO:0016020 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:5ukm, PDBe:5ukm, PDBj:5ukm
PDBsum5ukm
PubMed28323425
UniProtP21146|ARBK1_BOVIN Beta-adrenergic receptor kinase 1 (Gene Name=GRK2)

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