[English] 日本語
Yorodumi
- PDB-5ukl: Human GRK2 in complex with Gbetagamma subunits and CCG222886 (14bd) -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 5ukl
TitleHuman GRK2 in complex with Gbetagamma subunits and CCG222886 (14bd)
Components
  • (Guanine nucleotide-binding protein ...) x 2
  • Beta-adrenergic receptor kinase 1
KeywordsTRANSFERASE/TRANSFERASE INHIBITOR / kinase / inhibitor complex / TRANSFERASE-TRANSFERASE INHIBITOR complex
Function / homology
Function and homology information


negative regulation of the force of heart contraction by chemical signal / negative regulation of relaxation of smooth muscle / beta-adrenergic-receptor kinase / Edg-2 lysophosphatidic acid receptor binding / alpha-2A adrenergic receptor binding / beta-adrenergic receptor kinase activity / G protein-coupled receptor kinase activity / tachykinin receptor signaling pathway / negative regulation of striated muscle contraction / positive regulation of catecholamine secretion ...negative regulation of the force of heart contraction by chemical signal / negative regulation of relaxation of smooth muscle / beta-adrenergic-receptor kinase / Edg-2 lysophosphatidic acid receptor binding / alpha-2A adrenergic receptor binding / beta-adrenergic receptor kinase activity / G protein-coupled receptor kinase activity / tachykinin receptor signaling pathway / negative regulation of striated muscle contraction / positive regulation of catecholamine secretion / Activation of SMO / desensitization of G protein-coupled receptor signaling pathway / cytoplasmic side of mitochondrial outer membrane / regulation of the force of heart contraction / Calmodulin induced events / cardiac muscle contraction / viral genome replication / G protein-coupled receptor binding / receptor internalization / Olfactory Signaling Pathway / Activation of the phototransduction cascade / G beta:gamma signalling through PLC beta / Presynaptic function of Kainate receptors / Thromboxane signalling through TP receptor / G protein-coupled acetylcholine receptor signaling pathway / Activation of G protein gated Potassium channels / Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits / G-protein activation / Prostacyclin signalling through prostacyclin receptor / G beta:gamma signalling through CDC42 / Glucagon signaling in metabolic regulation / G beta:gamma signalling through BTK / Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1) / ADP signalling through P2Y purinoceptor 12 / photoreceptor disc membrane / Sensory perception of sweet, bitter, and umami (glutamate) taste / Glucagon-type ligand receptors / Adrenaline,noradrenaline inhibits insulin secretion / Vasopressin regulates renal water homeostasis via Aquaporins / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / G alpha (z) signalling events / cellular response to catecholamine stimulus / ADP signalling through P2Y purinoceptor 1 / ADORA2B mediated anti-inflammatory cytokines production / G beta:gamma signalling through PI3Kgamma / adenylate cyclase-activating dopamine receptor signaling pathway / Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding / GPER1 signaling / Cargo recognition for clathrin-mediated endocytosis / Inactivation, recovery and regulation of the phototransduction cascade / cellular response to prostaglandin E stimulus / G-protein beta-subunit binding / heterotrimeric G-protein complex / G alpha (12/13) signalling events / sensory perception of taste / presynapse / extracellular vesicle / signaling receptor complex adaptor activity / Thrombin signalling through proteinase activated receptors (PARs) / heart development / retina development in camera-type eye / GTPase binding / Ca2+ pathway / fibroblast proliferation / High laminar flow shear stress activates signaling by PIEZO1 and PECAM1:CDH5:KDR in endothelial cells / G alpha (i) signalling events / G alpha (s) signalling events / phospholipase C-activating G protein-coupled receptor signaling pathway / G alpha (q) signalling events / Ras protein signal transduction / Extra-nuclear estrogen signaling / cell population proliferation / protein kinase activity / postsynapse / cilium / G protein-coupled receptor signaling pathway / lysosomal membrane / GTPase activity / synapse / symbiont entry into host cell / protein-containing complex binding / signal transduction / extracellular exosome / ATP binding / membrane / plasma membrane / cytoplasm / cytosol
Similarity search - Function
Helix Hairpins - #1270 / Transducin (heterotrimeric G protein), gamma chain / G Protein Gi Gamma 2 / GPCR kinase / Regulator of G-protein Signalling 4, domain 2 / Regulator of G-protein Signalling 4; domain 2 / Regulator of G protein signaling domain / RGS domain / RGS domain profile. / Regulator of G protein signalling domain ...Helix Hairpins - #1270 / Transducin (heterotrimeric G protein), gamma chain / G Protein Gi Gamma 2 / GPCR kinase / Regulator of G-protein Signalling 4, domain 2 / Regulator of G-protein Signalling 4; domain 2 / Regulator of G protein signaling domain / RGS domain / RGS domain profile. / Regulator of G protein signalling domain / RGS, subdomain 2 / RGS domain superfamily / Pleckstrin-homology domain (PH domain)/Phosphotyrosine-binding domain (PTB) / PH-domain like / Extension to Ser/Thr-type protein kinases / AGC-kinase, C-terminal / AGC-kinase C-terminal domain profile. / PH domain / PH domain profile. / Pleckstrin homology domain. / YVTN repeat-like/Quinoprotein amine dehydrogenase / Pleckstrin homology domain / 7 Propeller / Methylamine Dehydrogenase; Chain H / Few Secondary Structures / Irregular / G-protein, gamma subunit / G-protein gamma subunit domain profile. / G-protein gamma-like domain / G-protein gamma-like domain superfamily / GGL domain / G protein gamma subunit-like motifs / GGL domain / G protein beta WD-40 repeat protein / Guanine nucleotide-binding protein, beta subunit / G-protein, beta subunit / Helix Hairpins / PH-like domain superfamily / WD domain, G-beta repeat / Roll / G-protein beta WD-40 repeat / WD40 repeat, conserved site / Phosphorylase Kinase; domain 1 / Trp-Asp (WD) repeats signature. / Phosphorylase Kinase; domain 1 / Transferase(Phosphotransferase) domain 1 / Transferase(Phosphotransferase); domain 1 / Serine/threonine-protein kinase, active site / Serine/Threonine protein kinases active-site signature. / Trp-Asp (WD) repeats profile. / Trp-Asp (WD) repeats circular profile. / WD40 repeats / WD40 repeat / Protein kinase domain / WD40-repeat-containing domain superfamily / Serine/Threonine protein kinases, catalytic domain / WD40/YVTN repeat-like-containing domain superfamily / Protein kinase, ATP binding site / Protein kinases ATP-binding region signature. / Protein kinase domain profile. / Protein kinase domain / Protein kinase-like domain superfamily / 2-Layer Sandwich / Orthogonal Bundle / Mainly Beta / Mainly Alpha / Alpha Beta
Similarity search - Domain/homology
Chem-SIX / Beta-adrenergic receptor kinase 1 / Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 / Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.15 Å
AuthorsCato, M.C. / Homan, K.T. / Tesmer, J.J.G.
Funding support United States, 12items
OrganizationGrant numberCountry
National Institutes of Health/National Heart, Lung, and Blood Institute (NIH/NHLBI)HL071818 United States
National Institutes of Health/National Heart, Lung, and Blood Institute (NIH/NHLBI)HL086865 United States
National Institutes of Health/National Heart, Lung, and Blood Institute (NIH/NHLBI)HL122416 United States
American Heart AssociationN014938 United States
American Heart Association15PRE22730028 United States
National Institutes of Health/National Heart, Lung, and Blood Institute (NIH/NHLBI)R37 HL061690 United States
National Institutes of Health/National Heart, Lung, and Blood Institute (NIH/NHLBI)P01 HL075443 United States
National Institutes of Health/National Heart, Lung, and Blood Institute (NIH/NHLBI)P01 HL108806 United States
National Institutes of Health/National Heart, Lung, and Blood Institute (NIH/NHLBI)P01 HL091799 United States
Center for Discovery of New Medicine, University of Michigan United States
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)5T32GM008597 United States
Michigan Economic Development Corporation and Michigan Technology Tri-Corridor Grant085P1000817 United States
CitationJournal: J. Med. Chem. / Year: 2017
Title: Structure-Based Design of Highly Selective and Potent G Protein-Coupled Receptor Kinase 2 Inhibitors Based on Paroxetine.
Authors: Waldschmidt, H.V. / Homan, K.T. / Cato, M.C. / Cruz-Rodriguez, O. / Cannavo, A. / Wilson, M.W. / Song, J. / Cheung, J.Y. / Koch, W.J. / Tesmer, J.J. / Larsen, S.D.
History
DepositionJan 23, 2017Deposition site: RCSB / Processing site: RCSB
Revision 1.0Apr 5, 2017Provider: repository / Type: Initial release
Revision 1.1Apr 26, 2017Group: Database references
Revision 1.2Sep 13, 2017Group: Author supporting evidence / Category: pdbx_audit_support / Item: _pdbx_audit_support.funding_organization
Revision 1.3Sep 27, 2017Group: Data collection / Refinement description / Category: diffrn_detector / software / Item: _diffrn_detector.detector
Revision 1.4Dec 4, 2019Group: Author supporting evidence / Derived calculations / Category: pdbx_audit_support / pdbx_struct_special_symmetry / Item: _pdbx_audit_support.funding_organization
Revision 1.5Oct 4, 2023Group: Data collection / Database references / Refinement description
Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / database_2 / pdbx_initial_refinement_model
Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Beta-adrenergic receptor kinase 1
B: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1
G: Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2
hetero molecules


Theoretical massNumber of molelcules
Total (without water)119,5365
Polymers119,0313
Non-polymers5052
Water6,990388
1


  • Idetical with deposited unit
  • defined by author&software
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area7090 Å2
ΔGint-50 kcal/mol
Surface area47220 Å2
MethodPISA
Unit cell
Length a, b, c (Å)194.255, 71.429, 111.259
Angle α, β, γ (deg.)90.000, 110.510, 90.000
Int Tables number5
Space group name H-MC121
Components on special symmetry positions
IDModelComponents
11A-801-

HOH

-
Components

-
Protein , 1 types, 1 molecules A

#1: Protein Beta-adrenergic receptor kinase 1 / Beta-ARK-1 / G-protein coupled receptor kinase 2


Mass: 74799.953 Da / Num. of mol.: 1 / Mutation: S670A
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: GRK2, ADRBK1, BARK, BARK1 / Plasmid: pFastBacDual / Production host: Trichoplusia ni (cabbage looper)
References: UniProt: P25098, beta-adrenergic-receptor kinase

-
Guanine nucleotide-binding protein ... , 2 types, 2 molecules BG

#2: Protein Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 / Transducin beta chain 1


Mass: 37285.734 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: GNB1 / Plasmid: pFastBacDual / Production host: Trichoplusia ni (cabbage looper) / References: UniProt: P62873
#3: Protein Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 / G gamma-I


Mass: 6945.089 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: GNG2 / Plasmid: pFastBacDual / Production host: Trichoplusia ni (cabbage looper) / References: UniProt: P59768

-
Non-polymers , 3 types, 390 molecules

#4: Chemical ChemComp-MG / MAGNESIUM ION


Mass: 24.305 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: Mg
#5: Chemical ChemComp-SIX / 2-{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


Mass: 480.531 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C26H29FN4O4
#6: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 388 / Source method: isolated from a natural source / Formula: H2O

-
Experimental details

-
Experiment

ExperimentMethod: X-RAY DIFFRACTION / Number of used crystals: 1

-
Sample preparation

CrystalDensity Matthews: 3.07 Å3/Da / Density % sol: 59.94 %
Crystal growTemperature: 277 K / Method: vapor diffusion, hanging drop / pH: 6
Details: 50 mM MES, 0.8-1.2 M sodium chloride, 8-16% PEG3350

-
Data collection

DiffractionMean temperature: 100 K
Diffraction sourceSource: SYNCHROTRON / Site: APS / Beamline: 21-ID-G / Wavelength: 0.97856 Å
DetectorType: MARMOSAIC 300 mm CCD / Detector: CCD / Date: Jul 28, 2014
RadiationMonochromator: diamond(111) / Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.97856 Å / Relative weight: 1
ReflectionResolution: 2.15→50 Å / Num. obs: 77337 / % possible obs: 100 % / Redundancy: 18.3 % / Rmerge(I) obs: 0.161 / Net I/σ(I): 24.9
Reflection shell
Resolution (Å)Redundancy (%)CC1/2Diffraction-ID% possible allRmerge(I) obs
2.15-2.1911.20.7571100
2.19-2.2313.80.8341100
2.23-2.2715.50.881100
2.27-2.3216.60.9051100
2.32-2.3717.20.9371100
2.37-2.4217.70.951100
2.42-2.4818.20.95611000.962
2.48-2.5518.80.97111000.872
2.55-2.6219.50.97811000.817
2.62-2.71200.98311000.702
2.71-2.8120.20.98711000.554
2.81-2.9220.20.99111000.422
2.92-3.0520.20.99311000.331
3.05-3.2120.20.99511000.245
3.21-3.4120.20.99611000.18
3.41-3.68200.99611000.145
3.68-4.0519.50.99711000.122
4.05-4.6318.80.99711000.103
4.63-5.8319.10.99811000.084
5.83-5018.80.997199.80.078

-
Processing

Software
NameVersionClassification
DENZOdata reduction
SCALEPACKdata scaling
PHASERphasing
REFMAC5.8.0151refinement
PDB_EXTRACT3.22data extraction
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: PDB entry 3V5W

3v5w


Resolution: 2.15→30 Å / Cor.coef. Fo:Fc: 0.964 / Cor.coef. Fo:Fc free: 0.94 / SU B: 11.331 / SU ML: 0.142 / SU R Cruickshank DPI: 0.1894 / Cross valid method: THROUGHOUT / σ(F): 0 / ESU R: 0.189 / ESU R Free: 0.172 / Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS
RfactorNum. reflection% reflectionSelection details
Rfree0.2275 3884 5 %RANDOM
Rwork0.1821 ---
obs0.1844 73370 99.03 %-
Solvent computationIon probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.2 Å
Displacement parametersBiso max: 160.3 Å2 / Biso mean: 55.457 Å2 / Biso min: 22.11 Å2
Baniso -1Baniso -2Baniso -3
1--0.23 Å20 Å2-0.19 Å2
2---0.53 Å2-0 Å2
3---0.7 Å2
Refinement stepCycle: final / Resolution: 2.15→30 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms8249 0 36 388 8673
Biso mean--69.5 46.51 -
Num. residues----1031
Refine LS restraints
Refine-IDTypeDev idealDev ideal targetNumber
X-RAY DIFFRACTIONr_bond_refined_d0.0180.0198475
X-RAY DIFFRACTIONr_bond_other_d0.0020.028043
X-RAY DIFFRACTIONr_angle_refined_deg1.9021.96111429
X-RAY DIFFRACTIONr_angle_other_deg1.069318521
X-RAY DIFFRACTIONr_dihedral_angle_1_deg7.0951031
X-RAY DIFFRACTIONr_dihedral_angle_2_deg33.49323.723411
X-RAY DIFFRACTIONr_dihedral_angle_3_deg16.83151522
X-RAY DIFFRACTIONr_dihedral_angle_4_deg17.6741567
X-RAY DIFFRACTIONr_chiral_restr0.1120.21226
X-RAY DIFFRACTIONr_gen_planes_refined0.0090.029580
X-RAY DIFFRACTIONr_gen_planes_other0.0020.022009
LS refinement shellResolution: 2.149→2.205 Å / Rfactor Rfree error: 0 / Total num. of bins used: 20
RfactorNum. reflection% reflection
Rfree0.312 227 -
Rwork0.299 4753 -
all-4980 -
obs--87.41 %
Refinement TLS params.

Method: refined / Refine-ID: X-RAY DIFFRACTION

IDL11 (°2)L12 (°2)L13 (°2)L22 (°2)L23 (°2)L33 (°2)S11 (Å °)S12 (Å °)S13 (Å °)S21 (Å °)S22 (Å °)S23 (Å °)S31 (Å °)S32 (Å °)S33 (Å °)T11 (Å2)T12 (Å2)T13 (Å2)T22 (Å2)T23 (Å2)T33 (Å2)Origin x (Å)Origin y (Å)Origin z (Å)
10.369-0.07210.12730.03080.06591.14910.0786-0.03920.12-0.02040.0151-0.00410.06220.0658-0.09370.21230.00520.04260.23450.00350.1689-3.909634.612652.3807
20.9468-0.45461.27010.2499-0.59781.79510.60920.4501-0.2804-0.2338-0.17070.16610.86660.7309-0.43860.53920.4393-0.15950.4479-0.19780.18511.06815.426743.0468
30.5277-0.12441.05680.047-0.30542.37880.50170.0536-0.1482-0.1354-0.00090.10880.94220.1628-0.50080.63220.0423-0.25750.0662-0.03650.3585.6372-1.974966.3362
40.6307-0.24840.80220.1564-0.42641.58390.09620.06110.0814-0.0291-0.02880.05640.38210.2685-0.06740.26560.08540.01960.29890.01520.1453-5.98328.052314.9447
50.6324-0.15790.24390.3022-0.3030.44090.0258-0.04310.0423-0.01490.01610.04370.02250.0011-0.04190.17360.01650.060.23380.02130.1748-28.422348.2207-3.21
Refinement TLS group
IDRefine-IDRefine TLS-IDAuth asym-IDAuth seq-ID
1X-RAY DIFFRACTION1A31 - 184
2X-RAY DIFFRACTION1A513 - 547
3X-RAY DIFFRACTION2A185 - 270
4X-RAY DIFFRACTION2A496 - 512
5X-RAY DIFFRACTION2A702
6X-RAY DIFFRACTION3A271 - 484
7X-RAY DIFFRACTION4A548 - 671
8X-RAY DIFFRACTION5B2 - 340
9X-RAY DIFFRACTION5G8 - 69

+
About Yorodumi

-
News

-
Feb 9, 2022. New format data for meta-information of EMDB entries

New format data for meta-information of EMDB entries

  • Version 3 of the EMDB header file is now the official format.
  • The previous official version 1.9 will be removed from the archive.

Related info.:EMDB header

External links:wwPDB to switch to version 3 of the EMDB data model

-
Aug 12, 2020. Covid-19 info

Covid-19 info

URL: https://pdbj.org/emnavi/covid19.php

New page: Covid-19 featured information page in EM Navigator.

Related info.:Covid-19 info / Mar 5, 2020. Novel coronavirus structure data

+
Mar 5, 2020. Novel coronavirus structure data

Novel coronavirus structure data

Related info.:Yorodumi Speices / Aug 12, 2020. Covid-19 info

External links:COVID-19 featured content - PDBj / Molecule of the Month (242)：Coronavirus Proteases

+
Jan 31, 2019. EMDB accession codes are about to change! (news from PDBe EMDB page)

EMDB accession codes are about to change! (news from PDBe EMDB page)

  • The allocation of 4 digits for EMDB accession codes will soon come to an end. Whilst these codes will remain in use, new EMDB accession codes will include an additional digit and will expand incrementally as the available range of codes is exhausted. The current 4-digit format prefixed with “EMD-” (i.e. EMD-XXXX) will advance to a 5-digit format (i.e. EMD-XXXXX), and so on. It is currently estimated that the 4-digit codes will be depleted around Spring 2019, at which point the 5-digit format will come into force.
  • The EM Navigator/Yorodumi systems omit the EMD- prefix.

Related info.:Q: What is EMD? / ID/Accession-code notation in Yorodumi/EM Navigator

External links:EMDB Accession Codes are Changing Soon! / Contact to PDBj

+
Jul 12, 2017. Major update of PDB

Major update of PDB

  • wwPDB released updated PDB data conforming to the new PDBx/mmCIF dictionary.
  • This is a major update changing the version number from 4 to 5, and with Remediation, in which all the entries are updated.
  • In this update, many items about electron microscopy experimental information are reorganized (e.g. em_software).
  • Now, EM Navigator and Yorodumi are based on the updated data.

External links:wwPDB Remediation / Enriched Model Files Conforming to OneDep Data Standards Now Available in the PDB FTP Archive

-
Yorodumi

Thousand views of thousand structures

  • Yorodumi is a browser for structure data from EMDB, PDB, SASBDB, etc.
  • This page is also the successor to EM Navigator detail page, and also detail information page/front-end page for Omokage search.
  • The word "yorodu" (or yorozu) is an old Japanese word meaning "ten thousand". "mi" (miru) is to see.

Related info.:EMDB / PDB / SASBDB / Comparison of 3 databanks / Yorodumi Search / Aug 31, 2016. New EM Navigator & Yorodumi / Yorodumi Papers / Jmol/JSmol / Function and homology information / Changes in new EM Navigator and Yorodumi

Read more