5UUU

Design, Synthesis, and Evaluation of the First Selective and Potent G-protein-Coupled Receptor Kinase 2 (GRK2) Inhibitor for the Potential Treatment of Heart Failure

External Resource: Annotation

Domain Annotation: ECOD Classification
Protein Family Annotation
Gene Ontology: Gene Product Annotation
InterPro: Protein Family Classification
Pharos: Disease Associations

Domain Annotation: ECOD Classification ECOD Database Homepage

Chains	Family Name	Domain Identifier	Architecture	Possible Homology	Homology	Topology	Family	Provenance Source (Version)
A	PF00069	e5uuuA1	A: a+b complex topology	X: Protein kinase/SAICAR synthase/ATP-grasp (From Homology)	H: Protein kinase/SAICAR synthase/ATP-grasp	T: Protein kinase	F: PF00069	ECOD (1.6)

Protein Family Annotation Pfam Database Homepage

Chains	Accession	Name	Description	Comments	Source
A	PF00615	Regulator of G protein signaling domain (RGS)	Regulator of G protein signaling domain	RGS family members are GTPase-activating proteins for heterotrimeric G-protein alpha-subunits.	Domain
A	PF00069	Protein kinase domain (Pkinase)	Protein kinase domain	-	Domain

Gene Ontology: Gene Product Annotation Gene Ontology Database Homepage

Chains	Polymer	Molecular Function	Biological Process	Cellular Component
A	Beta-adrenergic receptor kinase 1	catalytic activity, acting on a protein beta-adrenergic receptor kinase activity kinase activity protein kinase activity transferase activity catalytic activity phosphotransferase activity, alcohol group as acceptor transferase activity, transferring phosphorus-containing groups Edg-2 lysophosphatidic acid receptor binding protein binding binding signaling receptor binding endothelial differentiation G protein-coupled receptor binding G protein-coupled receptor binding catalytic activity, acting on a protein beta-adrenergic receptor kinase activity kinase activity protein kinase activity transferase activity catalytic activity phosphotransferase activity, alcohol group as acceptor transferase activity, transferring phosphorus-containing groups Edg-2 lysophosphatidic acid receptor binding protein binding binding signaling receptor binding endothelial differentiation G protein-coupled receptor binding G protein-coupled receptor binding adenyl ribonucleotide binding nucleotide binding purine ribonucleotide binding purine ribonucleoside triphosphate binding nucleoside phosphate binding ion binding purine nucleotide binding organic cyclic compound binding anion binding adenyl nucleotide binding ATP binding heterocyclic compound binding carbohydrate derivative binding ribonucleotide binding small molecule binding adrenergic receptor binding alpha-2A adrenergic receptor binding protein serine/threonine kinase activity G protein-coupled receptor kinase activity	developmental process heart development multicellular organism development multicellular organismal process anatomical structure development animal organ development circulatory system development system development system process regulation of biological process regulation of system process biological regulation negative regulation of biological process muscle contraction developmental process heart development multicellular organism development multicellular organismal process anatomical structure development animal organ development circulatory system development system development system process regulation of biological process regulation of system process biological regulation negative regulation of biological process muscle contraction muscle system process regulation of muscle system process striated muscle contraction negative regulation of muscle contraction regulation of striated muscle contraction regulation of muscle contraction regulation of multicellular organismal process negative regulation of multicellular organismal process negative regulation of striated muscle contraction heart process regulation of heart contraction circulatory system process regulation of blood circulation regulation of biological quality heart contraction regulation of the force of heart contraction blood circulation localization import into cell receptor internalization transport cellular process receptor-mediated endocytosis endocytosis establishment of localization vesicle-mediated transport viral genome replication viral process viral life cycle cellular response to stimulus negative adaptation of signaling pathway regulation of cellular process response to stimulus negative regulation of signaling signaling desensitization of G protein-coupled receptor signaling pathway regulation of signal transduction negative regulation of G protein-coupled receptor signaling pathway negative regulation of cell communication cell communication negative regulation of cellular process signal transduction regulation of G protein-coupled receptor signaling pathway regulation of signaling negative regulation of response to stimulus negative regulation of signal transduction regulation of response to stimulus adaptation of signaling pathway regulation of cell communication G protein-coupled receptor signaling pathway monoamine transport regulation of localization nitrogen compound transport regulation of catecholamine secretion positive regulation of biological process organic hydroxy compound transport positive regulation of secretion by cell positive regulation of amine transport secretion by cell regulation of secretion by cell catecholamine transport positive regulation of secretion positive regulation of cellular process secretion regulation of transport positive regulation of catecholamine secretion organic substance transport export from cell regulation of secretion catecholamine secretion amine transport positive regulation of transport regulation of amine transport negative regulation of blood circulation negative regulation of heart contraction negative regulation of the force of heart contraction by chemical signal regulation of the force of heart contraction by chemical signal cardiac muscle contraction organonitrogen compound metabolic process protein phosphorylation phosphorylation cellular metabolic process primary metabolic process peptidyl-serine modification organic substance metabolic process peptidyl-serine phosphorylation macromolecule modification peptidyl-amino acid modification phosphate-containing compound metabolic process metabolic process protein metabolic process macromolecule metabolic process protein modification process phosphorus metabolic process tachykinin receptor signaling pathway negative regulation of relaxation of smooth muscle relaxation of smooth muscle negative regulation of relaxation of muscle relaxation of muscle regulation of relaxation of smooth muscle regulation of relaxation of muscle biological process involved in interspecies interaction between organisms symbiont entry into host cell symbiont entry into host biological process involved in interaction with host biological process involved in symbiotic interaction cellular response to nitrogen compound response to organic substance synaptic signaling cellular response to acetylcholine response to oxygen-containing compound cell-cell signaling response to nitrogen compound acetylcholine receptor signaling pathway postsynaptic signal transduction cellular response to oxygen-containing compound cellular response to chemical stimulus G protein-coupled acetylcholine receptor signaling pathway response to chemical response to acetylcholine	membrane-bounded organelle cell projection organelle cilium cellular anatomical entity plasma membrane bounded cell projection membrane intracellular anatomical structure cytoplasm cytosol cell periphery plasma membrane presynapse synapse membrane-bounded organelle cell projection organelle cilium cellular anatomical entity plasma membrane bounded cell projection membrane intracellular anatomical structure cytoplasm cytosol cell periphery plasma membrane presynapse synapse cell junction postsynapse

InterPro: Protein Family Classification InterPro Database Homepage

Chains	Accession	Name	Type
A	IPR016137	RGS domain	Domain
A	IPR017441	Protein kinase, ATP binding site	Binding Site
A	IPR001849	Pleckstrin homology domain	Domain
A	IPR036305	RGS domain superfamily	Homologous Superfamily
A	IPR000719	Protein kinase domain	Domain
A	IPR011993	PH-like domain superfamily	Homologous Superfamily
A	IPR000961	AGC-kinase, C-terminal	Domain
A	IPR044926	RGS, subdomain 2	Homologous Superfamily
A	IPR011009	Protein kinase-like domain superfamily	Homologous Superfamily
A	IPR000239	GPCR kinase	Family
A	IPR008271	Serine/threonine-protein kinase, active site	Active Site

Pharos: Disease Associations Pharos Homepage Annotation

Chains	Drug Target	Associated Disease
A	Pharos: P25098	allergic contact dermatitis Cardiomegaly cardiovascular disease congenital abnormality hypertensive disorder congestive heart failure rheumatoid arthritis cardiomyopathy prostate carcinoma subependymal giant cell astrocytoma diabetes mellitus osteosarcoma psoriasis chronic obstructive pulmonary disease heart failure allergic contact dermatitis Cardiomegaly cardiovascular disease congenital abnormality hypertensive disorder congestive heart failure rheumatoid arthritis cardiomyopathy prostate carcinoma subependymal giant cell astrocytoma diabetes mellitus osteosarcoma psoriasis chronic obstructive pulmonary disease heart failure large cell medulloblastoma ovarian cancer colorectal adenocarcinoma depressive disorder

RCSB PDB Core Operations are funded by the National Science Foundation (DBI-1832184), the US Department of Energy (DE-SC0019749), and the National Cancer Institute, National Institute of Allergy and Infectious Diseases, and National Institute of General Medical Sciences of the National Institutes of Health under grant R01GM133198.