Structure of PDB 8jpc Chain G Binding Site BS02

Receptor Information

>8jpc Chain G (length=658) Species: 9913 (Bos taurus)

ADLEAVLADVSYLMAMEKSKATPAARASKKILLPEPSIRSVMQKYLEDRG
EVTFEKIFSQKLGYLLFRDFCLKHLEEAKPLVEFYEEIKKYEKLETEEER
LVCSREIFDTYIMKELLACSHPFSKSAIEHVQGHLVKKQVPPDLFQPYIE
EICQNLRGDVFQKFIESDKFTRFCQWKNVELNIHLTMNDFSVHRIIGRGG
FGEVYGCRKADTGKMYAMKCLDKKRIKMKQGETLALNERIMLSLVSTGDC
PFIVCMSYAFHTPDKLSFILDLMNGGDLHYHLSQHGVFSEPDMIFYAAEI
ILGLEHMHNRFVVYRDLKPANILLDEHGHVRISDLGLACDFSKKKPHASV
GTHGYMAPEVLQKGVAYDSSADWFSLGCMLFKLLRGHSPFRQHKTKDKHE
IDRMTLTMAVELPDSFSPELRSLLEGLLQRDVNRRLGCLGRGAQEVKESP
FFRDLDWQMVFLQKYPPPLIPPRGEVNAADAFDIGSFDEEDTKGIKLLDS
DQELYRNFPLTISERWQQEVAETVFDTINAETDRLEARKKTKNKQLGHEE
DYALGKDCIMHGYMSKMGNPFLTQWQRRYFYLFPNRLEWRGEGEAPQSLL
TMEEIQSVEETQIKERKCLLLKIRGGKQFVLQCDSDPELVQWKKELRDAY
REAQQLVQ

Ligand information

• Ligand ID: STU
• InChI: InChI=1S/C28H26N4O3/c1-28-26(34-3)17(29-2)12-20(35-28)31-18-10-6-4-8-14(18)22-23-16(13-30-27(23)33)21-15-9-5-7-11-19(15)32(28)25(21)24(22)31/h4-11,17,20,26,29H,12-13H2,1-3H3,(H,30,33)/t17-,20-,26-,28+/m1/s1
• InChIKey: HKSZLNNOFSGOKW-FYTWVXJKSA-N
• SMILES:
  OpenEye OEToolkits 1.5.0: CC12C(C(CC(O1)n3c4ccccc4c5c3c6n2c7ccccc7c6c8c5C(=O)NC8)NC)OC
  CACTVS 3.341: CN[CH]1C[CH]2O[C](C)([CH]1OC)n3c4ccccc4c5c6CNC(=O)c6c7c8ccccc8n2c7c35
  CACTVS 3.341: CN[C@@H]1C[C@H]2O[C@@](C)([C@@H]1OC)n3c4ccccc4c5c6CNC(=O)c6c7c8ccccc8n2c7c35
  ACDLabs 10.04: O=C5NCc4c2c3n(c1ccccc12)C8(OC(n6c3c(c45)c7ccccc67)CC(NC)C8OC)C
  OpenEye OEToolkits 1.5.0: C[C@@]12[C@@H]([C@@H](C[C@@H](O1)n3c4ccccc4c5c3c6n2c7ccccc7c6c8c5C(=O)NC8)NC)OC
• Formula: C28 H26 N4 O3
• Name: STAUROSPORINE
• ChEMBL: CHEMBL388978
• DrugBank: DB02010
• ZINC: ZINC000003814434
• PDB chain: 8jpc Chain G Residue 701

Receptor-Ligand Complex Structure

Structure summary

• PDB: 8jpc GPCR activation and GRK2 assembly by a biased intracellular agonist.
• Resolution: 3.07 Å
• Binding residue (original residue number in PDB): I197 G198 V205 A218 K220 D272 L273 M274 L324
• Binding residue (residue number reindexed from 1): I196 G197 V204 A217 K219 D271 L272 M273 L323
• Annotation score: 1

Enzymatic activity

• 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

External links

• PDB: RCSB:8jpc, PDBe:8jpc, PDBj:8jpc
• PDBsum: 8jpc
• PubMed: 37532940
• UniProt: P21146|ARBK1_BOVIN Beta-adrenergic receptor kinase 1 (Gene Name=GRK2)