Structure of PDB 5ukl Chain A Binding Site BS02

Receptor Information
>5ukl Chain A (length=630) Species: 9606 (Homo sapiens) [Search protein sequence] [Download receptor structure] [Download structure with residue number starting from 1] [View receptor structure]
KILLPEPSIRSVMQKYLEDRGEVTFEKIFSQKLGYLLFRDFCLNHLEEAR
PLVEFYEEIKKYEKLETEEERVARSREIFDSYIMKELLACSHPFSKSATE
HVQGHLGKKQVPPDLFQPYIEEICQNLRGDVFQKFIESDKFTRFCQWKNV
ELNIHLTMNDFSVHRIIGRGGFGEVYGCRKADTGKMYAMKCLDKKRIKMK
QGETLALNERIMLSLVSTGDCPFIVCMSYAFHTPDKLSFILDLMNGGDLH
YHLSQHGVFSEADMRFYAAEIILGLEHMHNRFVVYRDLKPANILLDEHGH
VRISDLGLACDFSKKKPHASVGTHGYMAPEVLQKGVAYDSSADWFSLGCM
LFKLLRGHSPFRQHKTKDKHEIDRMTLTMAVELPDSFSPELRSLLEGLLQ
RDVNRRLGCLGRGAQEVKESPFFRSLDWQMVFLQKYPPPLIPPRGEVNAA
DAFDIKLLDSDQELYRNFPLTISERWQQEVAETVFDTINAETDRLEARKK
AKNKQLGHEEDYALGKDCIMHGYMSKMGNPFLTQWQRRYFYLFPNRLEWR
GEGEAPQSLLTMEEIQSVEETQIKERKCLLLKIRGGKQFILQCDSDPELV
QWKKELRDAYREAQQLVQRVPKMKNKPRAP
Ligand information
Ligand IDSIX
InChIInChI=1S/C26H29FN4O4/c27-23-3-1-18(9-19(23)10-26(32)29-8-5-17-12-30-31-13-17)22-6-7-28-14-20(22)15-33-21-2-4-24-25(11-21)35-16-34-24/h1-4,9,11-13,20,22,28H,5-8,10,14-16H2,(H,29,32)(H,30,31)/t20-,22-/m0/s1
InChIKeyUWGQNVKEQMCXMS-UNMCSNQZSA-N
SMILES
SoftwareSMILES
CACTVS 3.385Fc1ccc(cc1CC(=O)NCCc2c[nH]nc2)[CH]3CCNC[CH]3COc4ccc5OCOc5c4
ACDLabs 12.01O=C(NCCc1cnnc1)Cc5cc(C2CCNCC2COc3ccc4c(c3)OCO4)ccc5F
OpenEye OEToolkits 2.0.6c1cc(c(cc1[C@@H]2CCNC[C@H]2COc3ccc4c(c3)OCO4)CC(=O)NCCc5c[nH]nc5)F
CACTVS 3.385Fc1ccc(cc1CC(=O)NCCc2c[nH]nc2)[C@@H]3CCNC[C@H]3COc4ccc5OCOc5c4
OpenEye OEToolkits 2.0.6c1cc(c(cc1C2CCNCC2COc3ccc4c(c3)OCO4)CC(=O)NCCc5c[nH]nc5)F
FormulaC26 H29 F N4 O4
Name2-{5-[(3S,4R)-3-{[(2H-1,3-benzodioxol-5-yl)oxy]methyl}piperidin-4-yl]-2-fluorophenyl}-N-[2-(1H-pyrazol-4-yl)ethyl]acetamide
ChEMBLCHEMBL4070290
DrugBank
ZINC
PDB chain5ukl Chain A Residue 702 [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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PDB5ukl Structure-Based Design of Highly Selective and Potent G Protein-Coupled Receptor Kinase 2 Inhibitors Based on Paroxetine.
Resolution2.15 Å
Binding residue
(original residue number in PDB)		R199 G200 F202 G203 V205 A218 V255 M274 D278 A321 A482
Binding residue
(residue number reindexed from 1)		R169 G170 F172 G173 V175 A188 V225 M244 D248 A291 A452
Annotation score1
Binding affinityMOAD: ic50=0.63uM
PDBbind-CN: -logKd/Ki=6.20,IC50=0.63uM
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: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:5ukl, PDBe:5ukl, PDBj:5ukl
PDBsum5ukl
PubMed28323425
UniProtP25098|ARBK1_HUMAN Beta-adrenergic receptor kinase 1 (Gene Name=GRK2)

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