Structure of PDB 5he1 Chain A Binding Site BS01

Receptor Information
>5he1 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]
SKKILLPEPSIRSVMQKYLEDRGEVTFEKIFSQKLGYLLFRDFCLNHLEE
ARPLVEFYEEIKKYEKLETEEERVARSREIFDSYIMKELLACSHPFSKSA
TEHVQGHLGKKQVPPDLFQPYIEEICQNLRGDVFQKFIESDKFTRFCQWK
NVELNIHLTMNDFSVHRIIGRGGFGEVYGCRKADTGKMYAMKCLDKKRIK
MKQGETLALNERIMLSLVSTGDCPFIVCMSYAFHTPDKLSFILDLMNGGD
LHYHLSQHGVFSEADMRFYAAEIILGLEHMHNRFVVYRDLKPANILLDEH
GHVRISDLGLACDFSKKKPHASVGTHGYMAPEVLQKGVAYDSSADWFSLG
CMLFKLLRGHSPFRQHKTKDKHEIDRMTLTMAVELPDSFSPELRSLLEGL
LQRDVNRRLGCLGRGAQEVKESPFFRSLDWQMVFLQKYPPPLIPPTKGIK
LLDSDQELYRNFPLTISERWQQEVAETVFDTINAETDRLEARKKAKNKHE
EDYALGKDCIMHGYMSKMGNPFLTQWQRRYFYLFPNRLEWRGEGEAPQSL
LTMEEIQSVEETQIKERKCLLLKIRGGKQFILQCDSDPELVQWKKELRDA
YREAQQLVQRVPKMKNKP
Ligand information
Ligand IDZS2
InChIInChI=1S/C30H24FN7O3/c1-16-26(29(40)36-20-7-9-24-19(12-20)14-34-38-24)27(37-30(41)35-16)18-6-8-23(31)22(13-18)28(39)33-15-25-21-5-3-2-4-17(21)10-11-32-25/h2-14,27H,15H2,1H3,(H,33,39)(H,34,38)(H,36,40)(H2,35,37,41)/t27-/m0/s1
InChIKeyUGYAZGXSMRGKRD-MHZLTWQESA-N
SMILES
SoftwareSMILES
OpenEye OEToolkits 2.0.4CC1=C(C(NC(=O)N1)c2ccc(c(c2)C(=O)NCc3c4ccccc4ccn3)F)C(=O)Nc5ccc6c(c5)cn[nH]6
CACTVS 3.385CC1=C([CH](NC(=O)N1)c2ccc(F)c(c2)C(=O)NCc3nccc4ccccc34)C(=O)Nc5ccc6[nH]ncc6c5
OpenEye OEToolkits 2.0.4CC1=C([C@@H](NC(=O)N1)c2ccc(c(c2)C(=O)NCc3c4ccccc4ccn3)F)C(=O)Nc5ccc6c(c5)cn[nH]6
CACTVS 3.385CC1=C([C@@H](NC(=O)N1)c2ccc(F)c(c2)C(=O)NCc3nccc4ccccc34)C(=O)Nc5ccc6[nH]ncc6c5
FormulaC30 H24 F N7 O3
Name(4~{S})-4-[4-fluoranyl-3-(isoquinolin-1-ylmethylcarbamoyl)phenyl]-~{N}-(1~{H}-indazol-5-yl)-6-methyl-2-oxidanylidene-3,4-dihydro-1~{H}-pyrimidine-5-carboxamide
ChEMBL
DrugBank
ZINCZINC000584905724
PDB chain5he1 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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PDB5he1 Structure-Based Design, Synthesis, and Biological Evaluation of Highly Selective and Potent G Protein-Coupled Receptor Kinase 2 Inhibitors.
Resolution3.15 Å
Binding residue
(original residue number in PDB)		G198 R199 G200 F202 G203 A218 L235 M274 A321 L324 S334 D335
Binding residue
(residue number reindexed from 1)		G170 R171 G172 F174 G175 A190 L207 M246 A293 L296 S306 D307
Annotation score1
Binding affinityPDBbind-CN: -logKd/Ki=6.55,IC50=0.28uM
BindingDB: IC50=2600nM
Enzymatic activity
Catalytic site (original residue number in PDB) D317 K319 N322 D335 K344 T353
Catalytic site (residue number reindexed from 1) D289 K291 N294 D307 K316 T325
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
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Biological Process
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Cellular Component
External links
PDB RCSB:5he1, PDBe:5he1, PDBj:5he1
PDBsum5he1
PubMed27050625
UniProtP25098|ARBK1_HUMAN Beta-adrenergic receptor kinase 1 (Gene Name=GRK2)

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