Structure of PDB 5he2 Chain A Binding Site BS01

Receptor Information
>5he2 Chain A (length=628) Species: 9913 (Bos taurus) [Search protein sequence] [Download receptor structure] [Download structure with residue number starting from 1] [View receptor structure]
KKILLPEPSIRSVMQKYLEDRGEVTFEKIFSQKLGYLLFRDFCLKHLEEA
KPLVEFYEEIKKYEKLETEEERLVCSREIFDTYIMKELLACSHPFSKSAI
EHVQGHLVKKQVPPDLFQPYIEEICQNLRGDVFQKFIESDKFTRFCQWKN
VELNIHLTMNDFSVHRIIGRGGFGEVYGCRKADTGKMYAMKCLDKKRIKM
KQGETLALNERIMLSLVSTGDCPFIVCMSYAFHTPDKLSFILDLMNGGDL
HYHLSQHGVFSEADMRFYAAEIILGLEHMHNRFVVYRDLKPANILLDEHG
HVRISDLGLACDFSKKKPHASVGTHGYMAPEVLQKGVAYDSSADWFSLGC
MLFKLLRGHSPFRQHKTKDKHEIDRMTLTMAVELPDSFSPELRSLLEGLL
QRDVNRRLGCLGRGAQEVKESPFFRSLDWQMVFLQKYPPPLIPPRGSFDE
EDTKGIKLLDSDQELYRNFPLTISERWQQEVAETVFDTINAETDRLEARK
KTKNKQLGHEEDYALGKDCIMHGYMSKMGNPFLTQWQRRYFYLFPNRLEW
RGEGEAPQSLLTMEEIQSVEETQIKERKCLLLKIRGGKQFVLQCDSDPEL
VQWKKELRDAYREAQQLVQRVPKMKNKP
Ligand information
Ligand IDF0S
InChIInChI=1S/C29H27FN6O5/c1-15-25(28(38)34-18-8-10-22-17(11-18)13-32-36-22)26(35-29(39)33-15)16-7-9-21(30)19(12-16)27(37)31-14-20-23(40-2)5-4-6-24(20)41-3/h4-13,26H,14H2,1-3H3,(H,31,37)(H,32,36)(H,34,38)(H2,33,35,39)/t26-/m0/s1
InChIKeyKQJWWWZXJNOLQF-SANMLTNESA-N
SMILES
SoftwareSMILES
OpenEye OEToolkits 2.0.4CC1=C([C@@H](NC(=O)N1)c2ccc(c(c2)C(=O)NCc3c(cccc3OC)OC)F)C(=O)Nc4ccc5c(c4)cn[nH]5
CACTVS 3.385COc1cccc(OC)c1CNC(=O)c2cc(ccc2F)[C@@H]3NC(=O)NC(=C3C(=O)Nc4ccc5[nH]ncc5c4)C
CACTVS 3.385COc1cccc(OC)c1CNC(=O)c2cc(ccc2F)[CH]3NC(=O)NC(=C3C(=O)Nc4ccc5[nH]ncc5c4)C
OpenEye OEToolkits 2.0.4CC1=C(C(NC(=O)N1)c2ccc(c(c2)C(=O)NCc3c(cccc3OC)OC)F)C(=O)Nc4ccc5c(c4)cn[nH]5
FormulaC29 H27 F N6 O5
Name(4~{S})-4-[3-[(2,6-dimethoxyphenyl)methylcarbamoyl]-4-fluoranyl-phenyl]-~{N}-(1~{H}-indazol-5-yl)-6-methyl-2-oxidanylidene-3,4-dihydro-1~{H}-pyrimidine-5-carboxamide
ChEMBL
DrugBank
ZINCZINC000584905542
PDB chain5he2 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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PDB5he2 Structure-Based Design, Synthesis, and Biological Evaluation of Highly Selective and Potent G Protein-Coupled Receptor Kinase 2 Inhibitors.
Resolution2.79 Å
Binding residue
(original residue number in PDB)		I197 R199 G200 F202 G203 A218 L222 M274 L324 S334 D335 G337 L338
Binding residue
(residue number reindexed from 1)		I168 R170 G171 F173 G174 A189 L193 M245 L295 S305 D306 G308 L309
Annotation score1
Binding affinityPDBbind-CN: -logKd/Ki=6.89,IC50=0.13uM
BindingDB: IC50=130nM
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: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

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Molecular Function
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Biological Process
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Cellular Component
External links
PDB RCSB:5he2, PDBe:5he2, PDBj:5he2
PDBsum5he2
PubMed27050625
UniProtP21146|ARBK1_BOVIN Beta-adrenergic receptor kinase 1 (Gene Name=GRK2)

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