[English] 日本語
Yorodumi
- PDB-7oy5: Crystal structure of GSK3Beta in complex with ARN25068 -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 7oy5
TitleCrystal structure of GSK3Beta in complex with ARN25068
ComponentsGlycogen synthase kinase-3 beta
KeywordsTRANSFERASE / Inhibitor / complex / GSK-3B
Function / homology
Function and homology information


regulation of microtubule anchoring at centrosome / negative regulation of glycogen (starch) synthase activity / neuron projection organization / negative regulation of mesenchymal stem cell differentiation / beta-catenin destruction complex disassembly / negative regulation of type B pancreatic cell development / superior temporal gyrus development / positive regulation of protein localization to cilium / negative regulation of glycogen biosynthetic process / negative regulation of dopaminergic neuron differentiation ...regulation of microtubule anchoring at centrosome / negative regulation of glycogen (starch) synthase activity / neuron projection organization / negative regulation of mesenchymal stem cell differentiation / beta-catenin destruction complex disassembly / negative regulation of type B pancreatic cell development / superior temporal gyrus development / positive regulation of protein localization to cilium / negative regulation of glycogen biosynthetic process / negative regulation of dopaminergic neuron differentiation / maintenance of cell polarity / positive regulation of protein localization to centrosome / : / positive regulation of mitochondrial outer membrane permeabilization involved in apoptotic signaling pathway / positive regulation of cilium assembly / negative regulation of protein acetylation / APC truncation mutants have impaired AXIN binding / AXIN missense mutants destabilize the destruction complex / Truncations of AMER1 destabilize the destruction complex / beta-catenin destruction complex / tau-protein kinase / CRMPs in Sema3A signaling / heart valve development / regulation of microtubule-based process / regulation of protein export from nucleus / Beta-catenin phosphorylation cascade / Signaling by GSK3beta mutants / CTNNB1 S33 mutants aren't phosphorylated / CTNNB1 S37 mutants aren't phosphorylated / CTNNB1 S45 mutants aren't phosphorylated / CTNNB1 T41 mutants aren't phosphorylated / Maturation of nucleoprotein / cellular response to interleukin-3 / Wnt signalosome / negative regulation of protein localization to nucleus / negative regulation of TOR signaling / regulation of long-term synaptic potentiation / Disassembly of the destruction complex and recruitment of AXIN to the membrane / Maturation of nucleoprotein / AKT phosphorylates targets in the cytosol / negative regulation of calcineurin-NFAT signaling cascade / positive regulation of cell-matrix adhesion / regulation of axon extension / dopamine receptor signaling pathway / negative regulation of phosphoprotein phosphatase activity / regulation of dendrite morphogenesis / regulation of axonogenesis / establishment of cell polarity / tau-protein kinase activity / glycogen metabolic process / ER overload response / Constitutive Signaling by AKT1 E17K in Cancer / protein kinase A catalytic subunit binding / dynactin binding / NF-kappaB binding / Regulation of HSF1-mediated heat shock response / epithelial to mesenchymal transition / canonical Wnt signaling pathway / negative regulation of osteoblast differentiation / negative regulation of protein-containing complex assembly / positive regulation of autophagy / regulation of microtubule cytoskeleton organization / regulation of cellular response to heat / cellular response to retinoic acid / extrinsic apoptotic signaling pathway / negative regulation of extrinsic apoptotic signaling pathway via death domain receptors / extrinsic apoptotic signaling pathway in absence of ligand / presynaptic modulation of chemical synaptic transmission / excitatory postsynaptic potential / negative regulation of insulin receptor signaling pathway / positive regulation of protein export from nucleus / positive regulation of protein ubiquitination / Ubiquitin-dependent degradation of Cyclin D / hippocampus development / positive regulation of cell differentiation / GSK3B and BTRC:CUL1-mediated-degradation of NFE2L2 / peptidyl-threonine phosphorylation / Degradation of GLI2 by the proteasome / GLI3 is processed to GLI3R by the proteasome / positive regulation of protein-containing complex assembly / Degradation of beta-catenin by the destruction complex / tau protein binding / negative regulation of canonical Wnt signaling pathway / B-WICH complex positively regulates rRNA expression / regulation of circadian rhythm / beta-catenin binding / positive regulation of GTPase activity / circadian rhythm / positive regulation of protein catabolic process / cellular response to amyloid-beta / Regulation of RUNX2 expression and activity / neuron projection development / positive regulation of neuron apoptotic process / positive regulation of proteasomal ubiquitin-dependent protein catabolic process / p53 binding / presynapse / positive regulation of protein binding / insulin receptor signaling pathway / negative regulation of neuron projection development / kinase activity
Similarity search - Function
Glycogen synthase kinase 3, catalytic domain / 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-39I / Glycogen synthase kinase-3 beta
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.57 Å
AuthorsTripathi, S.K. / Balboni, B. / Demuro, S. / DiMartino, R. / Giabbai, B. / Storici, P. / Ortega, J. / Girotto, S. / Cavalli, A.
CitationJournal: Eur.J.Med.Chem. / Year: 2022
Title: ARN25068, a versatile starting point towards triple GSK-3 beta /FYN/DYRK1A inhibitors to tackle tau-related neurological disorders.
Authors: Demuro, S. / Sauvey, C. / Tripathi, S.K. / Di Martino, R.M.C. / Shi, D. / Ortega, J.A. / Russo, D. / Balboni, B. / Giabbai, B. / Storici, P. / Girotto, S. / Abagyan, R. / Cavalli, A.
History
DepositionJun 23, 2021Deposition site: PDBE / Processing site: PDBE
Revision 1.0Mar 2, 2022Provider: repository / Type: Initial release
Revision 1.1Jan 31, 2024Group: Data collection / Refinement description
Category: chem_comp_atom / chem_comp_bond / pdbx_initial_refinement_model

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Glycogen synthase kinase-3 beta
B: Glycogen synthase kinase-3 beta
hetero molecules


Theoretical massNumber of molelcules
Total (without water)80,79910
Polymers79,8622
Non-polymers9388
Water1,33374
1


  • Idetical with deposited unit
  • defined by author&software
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area2720 Å2
ΔGint-75 kcal/mol
Surface area30110 Å2
MethodPISA
Unit cell
Length a, b, c (Å)82.570, 86.070, 178.590
Angle α, β, γ (deg.)90.000, 90.000, 90.000
Int Tables number19
Space group name H-MP212121

-
Components

#1: Protein Glycogen synthase kinase-3 beta / / GSK-3 beta / Serine/threonine-protein kinase GSK3B


Mass: 39930.922 Da / Num. of mol.: 2
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: GSK3B / Production host: Trichoplusia ni (cabbage looper)
References: UniProt: P49841, tau-protein kinase, non-specific serine/threonine protein kinase
#2: Chemical ChemComp-39I / ~{N}4-(3-cyclopropyl-1~{H}-pyrazol-5-yl)-~{N}2-(phenylmethyl)thieno[3,2-d]pyrimidine-2,4-diamine


Mass: 362.451 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C19H18N6S / Feature type: SUBJECT OF INVESTIGATION
#3: Chemical
ChemComp-CL / CHLORIDE ION / Chloride


Mass: 35.453 Da / Num. of mol.: 6 / Source method: obtained synthetically / Formula: Cl
#4: Water ChemComp-HOH / water / Water


Mass: 18.015 Da / Num. of mol.: 74 / Source method: isolated from a natural source / Formula: H2O
Has ligand of interestY

-
Experimental details

-
Experiment

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

-
Sample preparation

CrystalDensity Matthews: 3.97 Å3/Da / Density % sol: 69.04 %
Crystal growTemperature: 293 K / Method: vapor diffusion, hanging drop / pH: 7.4
Details: 15-20%PEG 3350, 50 mM Magnesium chloride, 20 mM Hepes 7.4

-
Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: ELETTRA / Beamline: 11.2C / Wavelength: 1 Å
DetectorType: DECTRIS PILATUS 6M / Detector: PIXEL / Date: Nov 17, 2020
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1 Å / Relative weight: 1
ReflectionResolution: 2.57→89.3 Å / Num. obs: 41531 / % possible obs: 99.9 % / Redundancy: 11.4 % / CC1/2: 0.96 / Net I/σ(I): 6.2
Reflection shellResolution: 2.57→2.67 Å / Redundancy: 9.6 % / Mean I/σ(I) obs: 1 / Num. unique obs: 4630 / CC1/2: 0.57 / % possible all: 99.9

-
Processing

Software
NameVersionClassification
REFMAC5.8.0258refinement
PDB_EXTRACT3.27data extraction
iMOSFLMdata reduction
Aimlessdata scaling
PHASERphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 6H0U

6h0u


Resolution: 2.57→89.29 Å / Cor.coef. Fo:Fc: 0.943 / Cor.coef. Fo:Fc free: 0.923 / SU B: 14.698 / SU ML: 0.28 / Cross valid method: THROUGHOUT / σ(F): 0 / ESU R: 0.326 / ESU R Free: 0.255 / Stereochemistry target values: MAXIMUM LIKELIHOOD
Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS U VALUES : REFINED INDIVIDUALLY
RfactorNum. reflection% reflectionSelection details
Rfree0.26 2084 5 %RANDOM
Rwork0.2186 ---
obs0.2207 39342 99.84 %-
Solvent computationIon probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.2 Å / Solvent model: MASK
Displacement parametersBiso max: 163.4 Å2 / Biso mean: 53.018 Å2 / Biso min: 21.57 Å2
Baniso -1Baniso -2Baniso -3
1--1.41 Å20 Å20 Å2
2--6.17 Å2-0 Å2
3----4.76 Å2
Refinement stepCycle: final / Resolution: 2.57→89.29 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms5247 0 58 75 5380
Biso mean--51.42 42.51 -
Num. residues----687
Refine LS restraints
Refine-IDTypeDev idealDev ideal targetNumber
X-RAY DIFFRACTIONr_bond_refined_d0.0090.0135618
X-RAY DIFFRACTIONr_bond_other_d0.0010.0175242
X-RAY DIFFRACTIONr_angle_refined_deg1.7521.6697659
X-RAY DIFFRACTIONr_angle_other_deg1.2831.57912138
X-RAY DIFFRACTIONr_dihedral_angle_1_deg7.2125686
X-RAY DIFFRACTIONr_dihedral_angle_2_deg33.22521.187278
X-RAY DIFFRACTIONr_dihedral_angle_3_deg17.20415905
X-RAY DIFFRACTIONr_dihedral_angle_4_deg16.0931541
X-RAY DIFFRACTIONr_chiral_restr0.070.2740
X-RAY DIFFRACTIONr_gen_planes_refined0.0070.026215
X-RAY DIFFRACTIONr_gen_planes_other0.0020.021198
LS refinement shellResolution: 2.57→2.634 Å / Rfactor Rfree error: 0
RfactorNum. reflection% reflection
Rfree0.4 149 -
Rwork0.4 2877 -
obs--99.61 %

+
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