[English] 日本語
Yorodumi
- PDB-5uvc: Design, Synthesis, and Evaluation of the First Selective and Pote... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 5uvc
TitleDesign, Synthesis, and Evaluation of the First Selective and Potent G-protein-Coupled Receptor Kinase 2 (GRK2) Inhibitor for the Potential Treatment of Heart Failure
ComponentsBeta-adrenergic receptor kinase 1G protein-coupled receptor kinase 2
KeywordsTRANSFERASE/TRANSFERASE INHIBITOR / Kinase / Inhibitor / Heart Failure / TRANSFERASE-TRANSFERASE INHIBITOR 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 / positive regulation of catecholamine secretion / tachykinin receptor signaling pathway / Activation of SMO ...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 / positive regulation of catecholamine secretion / tachykinin receptor signaling pathway / Activation of SMO / negative regulation of striated muscle contraction / desensitization of G protein-coupled receptor signaling pathway / regulation of the force of heart contraction / Calmodulin induced events / cardiac muscle contraction / viral genome replication / G protein-coupled receptor binding / G protein-coupled acetylcholine receptor signaling pathway / cilium / receptor internalization / Cargo recognition for clathrin-mediated endocytosis / presynapse / heart development / G alpha (s) signalling events / postsynapse / G alpha (q) signalling events / peptidyl-serine phosphorylation / protein kinase activity / symbiont entry into host cell / G protein-coupled receptor signaling pathway / ATP binding / membrane / plasma membrane / cytosol / cytoplasm
Similarity search - Function
GPCR kinase / Regulator of G protein signaling domain / RGS, subdomain 2 / RGS domain / RGS domain profile. / Regulator of G protein signalling domain / RGS domain superfamily / Extension to Ser/Thr-type protein kinases / AGC-kinase, C-terminal / AGC-kinase C-terminal domain profile. ...GPCR kinase / Regulator of G protein signaling domain / RGS, subdomain 2 / RGS domain / RGS domain profile. / Regulator of G protein signalling domain / RGS domain superfamily / 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. / Pleckstrin homology domain / PH-like domain superfamily / Serine/threonine-protein kinase, active site / Serine/Threonine protein kinases active-site signature. / Protein kinase domain / 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
Similarity search - Domain/homology
Chem-8PV / Beta-adrenergic receptor kinase 1
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / Resolution: 2.65 Å
AuthorsHoffman, I.D. / Lawson, J.D.
CitationJournal: J. Med. Chem. / Year: 2017
Title: Design, Synthesis, and Evaluation of the Highly Selective and Potent G-Protein-Coupled Receptor Kinase 2 (GRK2) Inhibitor for the Potential Treatment of Heart Failure.
Authors: Okawa, T. / Aramaki, Y. / Yamamoto, M. / Kobayashi, T. / Fukumoto, S. / Toyoda, Y. / Henta, T. / Hata, A. / Ikeda, S. / Kaneko, M. / Hoffman, I.D. / Sang, B.C. / Zou, H. / Kawamoto, T.
History
DepositionFeb 20, 2017Deposition site: RCSB / Processing site: RCSB
Revision 1.0Jul 26, 2017Provider: repository / Type: Initial release
Revision 1.1Sep 6, 2017Group: Database references / Category: citation
Item: _citation.journal_volume / _citation.page_first ..._citation.journal_volume / _citation.page_first / _citation.page_last / _citation.title
Revision 1.2Mar 6, 2024Group: Data collection / Database references / Category: chem_comp_atom / chem_comp_bond / database_2
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
hetero molecules


Theoretical massNumber of molelcules
Total (without water)63,8134
Polymers63,2361
Non-polymers5773
Water1,29772
1


  • Idetical with deposited unit
  • defined by author&software
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
MethodPISA
Unit cell
Length a, b, c (Å)113.157, 113.157, 95.427
Angle α, β, γ (deg.)90.000, 90.000, 90.000
Int Tables number94
Space group name H-MP42212
Components on special symmetry positions
IDModelComponents
11A-733-

HOH

21A-740-

HOH

31A-743-

HOH

41A-763-

HOH

-
Components

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


Mass: 63236.098 Da / Num. of mol.: 1 / Fragment: UNP residues 23-538
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: GRK2, ADRBK1, BARK, BARK1 / Production host: Baculovirus expression vector pFastBac1-HM
References: UniProt: P25098, beta-adrenergic-receptor kinase
#2: Chemical ChemComp-8PV / N-benzyl-3-({[5-(pyridin-4-yl)-4H-1,2,4-triazol-3-yl]methyl}amino)benzamide


Mass: 384.434 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C22H20N6O
#3: Chemical ChemComp-SO4 / SULFATE ION / Sulfate


Mass: 96.063 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: SO4
#4: Water ChemComp-HOH / water / Water


Mass: 18.015 Da / Num. of mol.: 72 / 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: 2.42 Å3/Da / Density % sol: 49.08 %
Crystal growTemperature: 273 K / Method: vapor diffusion, sitting drop / pH: 5.9
Details: 18% PEG MME 2000, 100mM MES pH 5.9, 17.5mM Ammonium Sulfate

-
Data collection

DiffractionMean temperature: 100 K
Diffraction sourceSource: SYNCHROTRON / Site: ALS / Beamline: 5.0.2 / Wavelength: 1 Å
DetectorType: ADSC QUANTUM 315 / Detector: CCD / Date: Sep 16, 2005
RadiationMonochromator: Double-crystal, Si(111) / Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1 Å / Relative weight: 1
ReflectionResolution: 2.65→50 Å / Num. obs: 18606 / % possible obs: 99.9 % / Redundancy: 5.7 % / Rmerge(I) obs: 0.115 / Χ2: 1.047 / Net I/σ(I): 9 / Num. measured all: 106790
Reflection shell
Resolution (Å)Redundancy (%)Rmerge(I) obsNum. unique allΧ2Diffraction-ID% possible all
2.65-2.744.80.52417910.93198.8
2.74-2.855.50.41718210.987199.9
2.85-2.985.70.32718301.0851100
2.98-3.145.70.25718281.1211100
3.14-3.345.80.18218341.0711100
3.34-3.660.14518321.0571100
3.6-3.966.20.12418691.0781100
3.96-4.536.10.1118811.0261100
4.53-5.715.90.08918951.018199.9
5.71-505.80.06920251.0691100

-
Processing

Software
NameVersionClassification
REFMAC5.8.0135refinement
HKL-2000data reduction
HKL-2000data scaling
PHASERphasing
RefinementResolution: 2.65→30 Å / Cor.coef. Fo:Fc: 0.934 / Cor.coef. Fo:Fc free: 0.906 / WRfactor Rfree: 0.2635 / WRfactor Rwork: 0.2183 / FOM work R set: 0.8063 / SU B: 26.176 / SU ML: 0.261 / SU R Cruickshank DPI: 0.7619 / SU Rfree: 0.3283 / Cross valid method: THROUGHOUT / σ(F): 0 / ESU R: 0.762 / ESU R Free: 0.328 / Stereochemistry target values: MAXIMUM LIKELIHOOD
Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS U VALUES : WITH TLS ADDED
RfactorNum. reflection% reflectionSelection details
Rfree0.2603 948 5.1 %RANDOM
Rwork0.2145 ---
obs0.2167 17607 99.61 %-
Solvent computationIon probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.2 Å / Solvent model: MASK
Displacement parametersBiso max: 117.24 Å2 / Biso mean: 60.002 Å2 / Biso min: 25.92 Å2
Baniso -1Baniso -2Baniso -3
1-0.98 Å20 Å20 Å2
2--0.98 Å2-0 Å2
3----1.95 Å2
Refinement stepCycle: final / Resolution: 2.65→30 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms3736 0 39 72 3847
Biso mean--76.7 47.69 -
Num. residues----457
Refine LS restraints
Refine-IDTypeDev idealDev ideal targetNumber
X-RAY DIFFRACTIONr_bond_refined_d0.0080.0193862
X-RAY DIFFRACTIONr_bond_other_d0.0010.023674
X-RAY DIFFRACTIONr_angle_refined_deg0.9861.9785194
X-RAY DIFFRACTIONr_angle_other_deg0.75938467
X-RAY DIFFRACTIONr_dihedral_angle_1_deg6.1125453
X-RAY DIFFRACTIONr_dihedral_angle_2_deg33.60223.386189
X-RAY DIFFRACTIONr_dihedral_angle_3_deg14.98815705
X-RAY DIFFRACTIONr_dihedral_angle_4_deg16.0851530
X-RAY DIFFRACTIONr_chiral_restr0.0570.2548
X-RAY DIFFRACTIONr_gen_planes_refined0.0040.0214276
X-RAY DIFFRACTIONr_gen_planes_other0.0010.02909
LS refinement shellResolution: 2.647→2.715 Å / Rfactor Rfree error: 0 / Total num. of bins used: 20
RfactorNum. reflection% reflection
Rfree0.349 78 -
Rwork0.273 1201 -
all-1279 -
obs--97.19 %
Refinement TLS params.Method: refined / Origin x: 7.1271 Å / Origin y: 27.4056 Å / Origin z: 11.7203 Å
111213212223313233
T0.1728 Å2-0.0208 Å20.0012 Å2-0.0475 Å2-0.0457 Å2--0.2431 Å2
L1.6911 °20.3918 °20.5772 °2-0.7158 °20.2312 °2--3.0168 °2
S0.0856 Å °-0.1351 Å °0.192 Å °0.081 Å °-0.1321 Å °0.0176 Å °-0.4816 Å °0.0883 Å °0.0465 Å °

+
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