[English] 日本語
Yorodumi
- PDB-6c2y: Human GRK2 in complex with Gbetagamma subunits and CCG257142 -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 6c2y
TitleHuman GRK2 in complex with Gbetagamma subunits and CCG257142
Components
  • 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
KeywordsTRANSFERASE/Signaling Protein / TRANSFERASE-Signaling Protein complex
Function / homology
Function and homology information


beta-adrenergic-receptor kinase / negative regulation of the force of heart contraction by chemical signal / negative regulation of relaxation of smooth muscle / beta-adrenergic receptor kinase activity / G protein-coupled receptor kinase activity / Edg-2 lysophosphatidic acid receptor binding / alpha-2A adrenergic receptor binding / tachykinin receptor signaling pathway / positive regulation of catecholamine secretion / Olfactory Signaling Pathway ...beta-adrenergic-receptor kinase / negative regulation of the force of heart contraction by chemical signal / negative regulation of relaxation of smooth muscle / beta-adrenergic receptor kinase activity / G protein-coupled receptor kinase activity / Edg-2 lysophosphatidic acid receptor binding / alpha-2A adrenergic receptor binding / tachykinin receptor signaling pathway / positive regulation of catecholamine secretion / Olfactory Signaling Pathway / Sensory perception of sweet, bitter, and umami (glutamate) taste / Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1) / Activation of SMO / negative regulation of striated muscle contraction / desensitization of G protein-coupled receptor signaling pathway / regulation of the force of heart contraction / Activation of the phototransduction cascade / Activation of G protein gated Potassium channels / G-protein activation / G beta:gamma signalling through PI3Kgamma / Prostacyclin signalling through prostacyclin receptor / G beta:gamma signalling through PLC beta / ADP signalling through P2Y purinoceptor 1 / Thromboxane signalling through TP receptor / Presynaptic function of Kainate receptors / G beta:gamma signalling through CDC42 / Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits / Glucagon-type ligand receptors / G alpha (12/13) signalling events / G beta:gamma signalling through BTK / ADP signalling through P2Y purinoceptor 12 / Adrenaline,noradrenaline inhibits insulin secretion / Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding / Thrombin signalling through proteinase activated receptors (PARs) / Ca2+ pathway / Calmodulin induced events / Extra-nuclear estrogen signaling / G alpha (z) signalling events / G alpha (s) signalling events / G alpha (q) signalling events / G alpha (i) signalling events / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / Vasopressin regulates renal water homeostasis via Aquaporins / cardiac muscle contraction / viral genome replication / G protein-coupled receptor binding / receptor internalization / cilium / G protein-coupled acetylcholine receptor signaling pathway / photoreceptor disc membrane / cellular response to catecholamine stimulus / adenylate cyclase-activating dopamine receptor signaling pathway / cellular response to prostaglandin E stimulus / G-protein beta-subunit binding / heterotrimeric G-protein complex / Cargo recognition for clathrin-mediated endocytosis / signaling receptor complex adaptor activity / heart development / presynapse / peptidyl-serine phosphorylation / G alpha (s) signalling events / G alpha (q) signalling events / postsynapse / protein kinase activity / symbiont entry into host cell / G protein-coupled receptor signaling pathway / GTPase activity / ATP binding / membrane / plasma membrane / cytosol / cytoplasm
Similarity search - Function
Helix Hairpins - #1270 / GPCR kinase / Transducin (heterotrimeric G protein), gamma chain / G Protein Gi Gamma 2 / 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 / GPCR kinase / Transducin (heterotrimeric G protein), gamma chain / G Protein Gi Gamma 2 / 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 / YVTN repeat-like/Quinoprotein amine dehydrogenase / Extension to Ser/Thr-type protein kinases / AGC-kinase, C-terminal / AGC-kinase C-terminal domain profile. / PH domain / 7 Propeller / Methylamine Dehydrogenase; Chain H / PH domain profile. / Pleckstrin homology domain. / Pleckstrin homology domain / 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 / Guanine nucleotide-binding protein, beta subunit / G-protein, beta subunit / Few Secondary Structures / Irregular / Helix Hairpins / PH-like domain superfamily / G-protein beta WD-40 repeat / Roll / WD40 repeat, conserved site / Trp-Asp (WD) repeats signature. / Trp-Asp (WD) repeats profile. / Trp-Asp (WD) repeats circular profile. / WD domain, G-beta repeat / WD40 repeats / WD40 repeat / Transferase(Phosphotransferase) domain 1 / Transferase(Phosphotransferase); domain 1 / Phosphorylase Kinase; domain 1 / Phosphorylase Kinase; domain 1 / WD40-repeat-containing domain superfamily / Serine/threonine-protein kinase, active site / Serine/Threonine protein kinases active-site signature. / Protein kinase domain / WD40/YVTN repeat-like-containing domain superfamily / Serine/Threonine protein kinases, catalytic domain / 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-EJS / Beta-adrenergic receptor kinase 1 / Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 / Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2
Similarity search - Component
Biological speciesHomo sapiens (human)
Bos taurus (cattle)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.74 Å
AuthorsBouley, R. / Tesmer, J.J.G.
Funding support United States, 1items
OrganizationGrant numberCountry
National Institutes of Health/National Heart, Lung, and Blood Institute (NIH/NHLBI)R01 HL071818 United States
CitationJournal: Bioorg. Med. Chem. Lett. / Year: 2018
Title: Utilizing a structure-based docking approach to develop potent G protein-coupled receptor kinase (GRK) 2 and 5 inhibitors.
Authors: Waldschmidt, H.V. / Bouley, R. / Kirchhoff, P.D. / Lee, P. / Tesmer, J.J.G. / Larsen, S.D.
History
DepositionJan 9, 2018Deposition site: RCSB / Processing site: RCSB
Revision 1.0Apr 25, 2018Provider: repository / Type: Initial release
Revision 1.1May 2, 2018Group: Data collection / Database references / Category: citation
Item: _citation.journal_volume / _citation.page_first / _citation.page_last
Revision 1.2Dec 4, 2019Group: Author supporting evidence / Category: pdbx_audit_support / Item: _pdbx_audit_support.funding_organization
Revision 1.3Oct 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)126,3044
Polymers125,7683
Non-polymers5371
Water75742
1


  • Idetical with deposited unit
  • defined by author&software
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area6720 Å2
ΔGint-46 kcal/mol
Surface area46240 Å2
MethodPISA
Unit cell
Length a, b, c (Å)60.557, 240.453, 212.796
Angle α, β, γ (deg.)90.00, 90.00, 90.00
Int Tables number20
Space group name H-MC2221

-
Components

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


Mass: 79676.641 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
Production host: Spodoptera aff. frugiperda 2 RZ-2014 (butterflies/moths)
References: UniProt: P25098, beta-adrenergic-receptor kinase
#2: Protein Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 / Transducin beta chain 1


Mass: 37416.930 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Bos taurus (cattle) / Gene: GNB1
Production host: Spodoptera aff. frugiperda 2 RZ-2014 (butterflies/moths)
References: UniProt: P62871
#3: Protein Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 / G gamma-I


Mass: 8673.959 Da / Num. of mol.: 1 / Mutation: C68S
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Bos taurus (cattle) / Gene: GNG2
Production host: Spodoptera aff. frugiperda 2 RZ-2014 (butterflies/moths)
References: UniProt: P63212
#4: Chemical ChemComp-EJS / (4R,5R,6S)-4-[4-fluoro-3-({[3-(methoxymethyl)-1,2,4-oxadiazol-5-yl]methyl}carbamoyl)phenyl]-N-(2H-indazol-5-yl)-6-methyl-2-oxohexahydropyrimidine-5-carboxamide


Mass: 536.515 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C25H25FN8O5 / Feature type: SUBJECT OF INVESTIGATION
#5: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 42 / 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: 3.08 Å3/Da / Density % sol: 60.06 %
Crystal growTemperature: 277 K / Method: vapor diffusion, hanging drop / pH: 6 / Details: 50 mM MES pH 6.0, 800 mM NaCl, 8% PEG 3350

-
Data collection

DiffractionMean temperature: 100 K
Diffraction sourceSource: SYNCHROTRON / Site: APS / Beamline: 21-ID-D / Wavelength: 1.0332 Å
DetectorType: DECTRIS EIGER X 9M / Detector: PIXEL / Date: Jun 7, 2017
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1.0332 Å / Relative weight: 1
ReflectionResolution: 2.74→48.32 Å / Num. obs: 40501 / % possible obs: 96 % / Redundancy: 14.1 % / CC1/2: 0.991 / Rmerge(I) obs: 0.3044 / Rrim(I) all: 0.3161 / Net I/σ(I): 5.62
Reflection shellResolution: 2.74→2.838 Å / Redundancy: 14.6 % / Rmerge(I) obs: 2.061 / Mean I/σ(I) obs: 1.17 / Num. unique obs: 4026 / CC1/2: 0.705 / Rrim(I) all: 2.137 / % possible all: 99

-
Processing

Software
NameVersionClassification
PHENIX(1.10.1_2155: ???)refinement
DIALSdata reduction
Aimlessdata scaling
PHASERphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 4PNK

4pnk


Resolution: 2.74→48.32 Å / SU ML: 0.4 / Cross valid method: FREE R-VALUE / σ(F): 1.33 / Phase error: 32.98
RfactorNum. reflection% reflection
Rfree0.2916 1965 4.95 %
Rwork0.2443 --
obs0.2466 39679 95.72 %
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å
Refinement stepCycle: LAST / Resolution: 2.74→48.32 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms8078 0 39 42 8159
Refine LS restraints
Refine-IDTypeDev idealNumber
X-RAY DIFFRACTIONf_bond_d0.0018286
X-RAY DIFFRACTIONf_angle_d0.43911168
X-RAY DIFFRACTIONf_dihedral_angle_d18.1933112
X-RAY DIFFRACTIONf_chiral_restr0.0381200
X-RAY DIFFRACTIONf_plane_restr0.0021446
LS refinement shell
Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkRefine-ID% reflection obs (%)
2.74-2.80850.38241420.38742553X-RAY DIFFRACTION93
2.8085-2.88450.39481260.38642636X-RAY DIFFRACTION94
2.8845-2.96930.40441290.36222622X-RAY DIFFRACTION95
2.9693-3.06520.38981350.35492679X-RAY DIFFRACTION97
3.0652-3.17470.42191330.33742718X-RAY DIFFRACTION97
3.1747-3.30180.31021510.32012679X-RAY DIFFRACTION97
3.3018-3.45210.34891410.29282720X-RAY DIFFRACTION97
3.4521-3.6340.32591570.26812731X-RAY DIFFRACTION98
3.634-3.86160.27641390.24492763X-RAY DIFFRACTION98
3.8616-4.15970.29931570.21952746X-RAY DIFFRACTION98
4.1597-4.57810.24781310.19082745X-RAY DIFFRACTION96
4.5781-5.240.24751200.17642345X-RAY DIFFRACTION83
5.24-6.59990.22761370.20962864X-RAY DIFFRACTION99
6.5999-53.2090.24551670.19292913X-RAY DIFFRACTION97
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)
13.15-1.2324-1.41292.38071.31373.4475-0.1734-0.5142-0.37060.2718-0.13940.87680.5075-0.44380.30750.5963-0.00730.28180.74210.0530.9766-44.57443.389631.7433
22.2995-0.67540.38352.5610.69141.4616-0.1572-0.09710.2037-0.42210.0708-0.61910.08750.6024-0.03160.57230.11090.1740.70090.01310.6073-17.4617.158716.0146
34.7671-2.2316-0.44515.1290.02753.59250.0554-0.81060.78860.0710.2487-1.0479-0.56950.9835-0.17090.544-0.10890.11690.8713-0.18930.728-21.392936.416232.6819
41.07780.729-0.34631.4570.33530.80520.14380.20340.0756-0.5791-0.0386-0.0934-0.0330.04970.05030.59480.06370.1660.36840.01560.4913-21.9099-21.65216.0189
51.4841-1.04980.08063.8302-0.64111.7430.04380.0648-0.221-0.36620.04320.34220.047-0.0318-0.07120.5372-0.01070.16340.4624-0.00930.5209-24.583-55.817326.7465
Refinement TLS group
IDRefine-IDRefine TLS-IDSelection detailsAuth asym-IDAuth seq-ID
1X-RAY DIFFRACTION1( CHAIN A AND ( RESID 30:184 OR RESID 513:548 OR RESID 812:821 ) )A30 - 184
2X-RAY DIFFRACTION1( CHAIN A AND ( RESID 30:184 OR RESID 513:548 OR RESID 812:821 ) )A513 - 548
3X-RAY DIFFRACTION1( CHAIN A AND ( RESID 30:184 OR RESID 513:548 OR RESID 812:821 ) )A812 - 821
4X-RAY DIFFRACTION2( CHAIN A AND ( RESID 185:274 OR RESID 493:512 OR RESID 701:701 ) )A185 - 274
5X-RAY DIFFRACTION2( CHAIN A AND ( RESID 185:274 OR RESID 493:512 OR RESID 701:701 ) )A493 - 512
6X-RAY DIFFRACTION2( CHAIN A AND ( RESID 185:274 OR RESID 493:512 OR RESID 701:701 ) )A701
7X-RAY DIFFRACTION3( CHAIN A AND RESID 275:474 )A275 - 474
8X-RAY DIFFRACTION4( CHAIN A AND RESID 551:668 )A551 - 668
9X-RAY DIFFRACTION5( CHAIN B AND ( RESID 2:340 OR RESID 401:417 ) ) OR ( CHAIN G AND ( RESID 7:63 OR RESID 101:101 ) )B2 - 340
10X-RAY DIFFRACTION5( CHAIN B AND ( RESID 2:340 OR RESID 401:417 ) ) OR ( CHAIN G AND ( RESID 7:63 OR RESID 101:101 ) )B401 - 417
11X-RAY DIFFRACTION5( CHAIN B AND ( RESID 2:340 OR RESID 401:417 ) ) OR ( CHAIN G AND ( RESID 7:63 OR RESID 101:101 ) )G7 - 63
12X-RAY DIFFRACTION5( CHAIN B AND ( RESID 2:340 OR RESID 401:417 ) ) OR ( CHAIN G AND ( RESID 7:63 OR RESID 101:101 ) )G101

+
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