[English] 日本語
Yorodumi
- PDB-3zrk: Identification of 2-(4-pyridyl)thienopyridinones as GSK-3beta inh... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 3zrk
TitleIdentification of 2-(4-pyridyl)thienopyridinones as GSK-3beta inhibitors
Components
  • GLYCOGEN SYNTHASE KINASE-3 BETA
  • PROTO-ONCOGENE FRAT1
KeywordsTRANSFERASE/PEPTIDE / TRANSFERASE-PEPTIDE COMPLEX / KINASE
Function / homology
Function and homology information


neuron projection organization / regulation of microtubule anchoring at centrosome / negative regulation of type B pancreatic cell development / negative regulation of glycogen (starch) synthase activity / negative regulation of mesenchymal stem cell differentiation / superior temporal gyrus development / positive regulation of protein localization to cilium / negative regulation of glycogen biosynthetic process / negative regulation of TORC2 signaling / negative regulation of dopaminergic neuron differentiation ...neuron projection organization / regulation of microtubule anchoring at centrosome / negative regulation of type B pancreatic cell development / negative regulation of glycogen (starch) synthase activity / negative regulation of mesenchymal stem cell differentiation / superior temporal gyrus development / positive regulation of protein localization to cilium / negative regulation of glycogen biosynthetic process / negative regulation of TORC2 signaling / negative regulation of dopaminergic neuron differentiation / maintenance of cell polarity / positive regulation of protein localization to centrosome / positive regulation of cilium assembly / beta-catenin destruction complex / CRMPs in Sema3A signaling / heart valve development / tau-protein kinase / APC truncation mutants have impaired AXIN binding / AXIN missense mutants destabilize the destruction complex / Truncations of AMER1 destabilize the destruction complex / 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 / positive regulation of mitochondrial outer membrane permeabilization involved in apoptotic signaling pathway / cellular response to interleukin-3 / Maturation of nucleoprotein / regulation of microtubule-based process / Wnt signalosome / regulation of long-term synaptic potentiation / negative regulation of TOR signaling / negative regulation of protein localization to nucleus / Disassembly of the destruction complex and recruitment of AXIN to the membrane / AKT phosphorylates targets in the cytosol / negative regulation of calcineurin-NFAT signaling cascade / regulation of axon extension / Maturation of nucleoprotein / tau-protein kinase activity / negative regulation of epithelial to mesenchymal transition / G protein-coupled dopamine receptor signaling pathway / molecular function inhibitor activity / positive regulation of cell-matrix adhesion / regulation of axonogenesis / regulation of dendrite morphogenesis / glycogen metabolic process / ER overload response / regulation of neuron projection development / Constitutive Signaling by AKT1 E17K in Cancer / establishment of cell polarity / protein kinase A catalytic subunit binding / dynactin binding / epithelial to mesenchymal transition / Regulation of HSF1-mediated heat shock response / NF-kappaB binding / canonical Wnt signaling pathway / negative regulation of osteoblast differentiation / positive regulation of protein binding / negative regulation of protein-containing complex assembly / negative regulation of extrinsic apoptotic signaling pathway via death domain receptors / regulation of cellular response to heat / extrinsic apoptotic signaling pathway / cellular response to retinoic acid / extrinsic apoptotic signaling pathway in absence of ligand / positive regulation of autophagy / Transcriptional and post-translational regulation of MITF-M expression and activity / presynaptic modulation of chemical synaptic transmission / regulation of microtubule cytoskeleton organization / negative regulation of cell migration / response to endoplasmic reticulum stress / positive regulation of protein export from nucleus / positive regulation of protein ubiquitination / Ubiquitin-dependent degradation of Cyclin D / excitatory postsynaptic potential / mitochondrion organization / hippocampus development / positive regulation of cell differentiation / positive regulation of protein-containing complex assembly / GSK3B and BTRC:CUL1-mediated-degradation of NFE2L2 / negative regulation of canonical Wnt signaling pathway / Degradation of GLI2 by the proteasome / GLI3 is processed to GLI3R by the proteasome / circadian rhythm / regulation of circadian rhythm / Degradation of beta-catenin by the destruction complex / beta-catenin binding / peptidyl-serine phosphorylation / B-WICH complex positively regulates rRNA expression / tau protein binding / Wnt signaling pathway / cellular response to amyloid-beta / neuron projection development / Regulation of RUNX2 expression and activity / positive regulation of protein catabolic process / p53 binding / kinase activity / insulin receptor signaling pathway / positive regulation of canonical Wnt signaling pathway
Similarity search - Function
Glycogen synthase kinase-3 binding protein / Glycogen synthase kinase-3 binding / Glycogen synthase kinase 3, catalytic domain / : / Phosphorylase Kinase; domain 1 / 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. ...Glycogen synthase kinase-3 binding protein / Glycogen synthase kinase-3 binding / Glycogen synthase kinase 3, catalytic domain / : / Phosphorylase Kinase; domain 1 / 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. / 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 / 2-Layer Sandwich / Orthogonal Bundle / Mainly Alpha / Alpha Beta
Similarity search - Domain/homology
2-(4-PYRIDINYL)FURO[3,2-C]PYRIDIN-4(5H)-ONE / Glycogen synthase kinase-3 beta / Proto-oncogene FRAT1
Similarity search - Component
Biological speciesHOMO SAPIENS (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / FOURIER SYNTHESIS / Resolution: 2.37 Å
AuthorsGentile, G. / Bernasconi, G. / Pozzan, A. / Merlo, G. / Marzorati, P. / Bamborough, P. / Bax, B. / Bridges, A. / Brough, C. / Carter, P. ...Gentile, G. / Bernasconi, G. / Pozzan, A. / Merlo, G. / Marzorati, P. / Bamborough, P. / Bax, B. / Bridges, A. / Brough, C. / Carter, P. / Cutler, G. / Neu, M. / Takada, M.
CitationJournal: Bioorg.Med.Chem.Lett. / Year: 2011
Title: Identification of 2-(4-Pyridyl)Thienopyridinones as Gsk-3Beta Inhibitors.
Authors: Gentile, G. / Bernasconi, G. / Pozzan, A. / Merlo, G. / Marzorati, P. / Bamborough, P. / Bax, B. / Bridges, A. / Brough, C. / Carter, P. / Cutler, G. / Neu, M. / Takada, M.
History
DepositionJun 16, 2011Deposition site: PDBE / Processing site: PDBE
Revision 1.0Jun 29, 2011Provider: repository / Type: Initial release
Revision 1.1Apr 25, 2012Group: Database references / Version format compliance
Revision 1.2Dec 20, 2023Group: Data collection / Database references ...Data collection / Database references / Derived calculations / Other / Refinement description
Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / database_2 / pdbx_database_status / pdbx_initial_refinement_model / struct_conn / struct_site
Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession ..._database_2.pdbx_DOI / _database_2.pdbx_database_accession / _pdbx_database_status.status_code_sf / _struct_conn.pdbx_leaving_atom_flag / _struct_site.pdbx_auth_asym_id / _struct_site.pdbx_auth_comp_id / _struct_site.pdbx_auth_seq_id
Revision 1.3Nov 20, 2024Group: Structure summary / Category: pdbx_entry_details / pdbx_modification_feature
Remark 700 SHEET DETERMINATION METHOD: DSSP THE SHEETS PRESENTED AS "AA" IN EACH CHAIN ON SHEET RECORDS BELOW ... SHEET DETERMINATION METHOD: DSSP THE SHEETS PRESENTED AS "AA" IN EACH CHAIN ON SHEET RECORDS BELOW IS ACTUALLY AN 6-STRANDED BARREL THIS IS REPRESENTED BY A 7-STRANDED SHEET IN WHICH THE FIRST AND LAST STRANDS ARE IDENTICAL. THE SHEETS PRESENTED AS "BA" IN EACH CHAIN ON SHEET RECORDS BELOW IS ACTUALLY AN 6-STRANDED BARREL THIS IS REPRESENTED BY A 7-STRANDED SHEET IN WHICH THE FIRST AND LAST STRANDS ARE IDENTICAL.

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: GLYCOGEN SYNTHASE KINASE-3 BETA
B: GLYCOGEN SYNTHASE KINASE-3 BETA
X: PROTO-ONCOGENE FRAT1
Y: PROTO-ONCOGENE FRAT1
hetero molecules


Theoretical massNumber of molelcules
Total (without water)92,89415
Polymers91,6174
Non-polymers1,27711
Water3,765209
1
A: GLYCOGEN SYNTHASE KINASE-3 BETA
X: PROTO-ONCOGENE FRAT1
hetero molecules


Theoretical massNumber of molelcules
Total (without water)46,3977
Polymers45,8092
Non-polymers5895
Water362
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area2440 Å2
ΔGint-53.5 kcal/mol
Surface area17870 Å2
MethodPISA
2
B: GLYCOGEN SYNTHASE KINASE-3 BETA
Y: PROTO-ONCOGENE FRAT1
hetero molecules


Theoretical massNumber of molelcules
Total (without water)46,4978
Polymers45,8092
Non-polymers6896
Water362
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area1970 Å2
ΔGint-42.6 kcal/mol
Surface area17900 Å2
MethodPISA
Unit cell
Length a, b, c (Å)151.896, 151.896, 201.119
Angle α, β, γ (deg.)90.00, 90.00, 120.00
Int Tables number155
Space group name H-MH32
Components on special symmetry positions
IDModelComponents
11B-1392-

SO4

-
Components

-
Protein / Protein/peptide , 2 types, 4 molecules ABXY

#1: Protein GLYCOGEN SYNTHASE KINASE-3 BETA / GSK-3 BETA


Mass: 42036.117 Da / Num. of mol.: 2 / Fragment: RESIDUES 23-393
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) HOMO SAPIENS (human) / Cell line (production host): SF9 / Production host: SPODOPTERA FRUGIPERDA (fall armyworm) / References: UniProt: P49841, tau-protein kinase
#2: Protein/peptide PROTO-ONCOGENE FRAT1 / FRAT / FREQUENTLY REARRANGED IN ADVANCED T-CELL LYMPHOMAS 1 / FRAT-1


Mass: 3772.434 Da / Num. of mol.: 2 / Fragment: RESIDUES 197-226
Source method: isolated from a genetically manipulated source
Details: FRATTIDE SEQUENCE CO-EXPRESSED IN BACULOVIRUS (DUAL EXPRESSION).
Source: (gene. exp.) HOMO SAPIENS (human) / Cell line (production host): SF9 / Production host: SPODOPTERA FRUGIPERDA (fall armyworm) / References: UniProt: Q92837

-
Non-polymers , 4 types, 220 molecules

#3: Chemical
ChemComp-SO4 / SULFATE ION


Mass: 96.063 Da / Num. of mol.: 6 / Source method: obtained synthetically / Formula: SO4
#4: Chemical ChemComp-GOL / GLYCEROL / GLYCERIN / PROPANE-1,2,3-TRIOL


Mass: 92.094 Da / Num. of mol.: 3 / Source method: obtained synthetically / Formula: C3H8O3
#5: Chemical ChemComp-ZRK / 2-(4-PYRIDINYL)FURO[3,2-C]PYRIDIN-4(5H)-ONE


Mass: 212.204 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C12H8N2O2
#6: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 209 / Source method: isolated from a natural source / Formula: H2O

-
Details

Has protein modificationY

-
Experimental details

-
Experiment

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

-
Sample preparation

CrystalDensity Matthews: 2.21 Å3/Da / Density % sol: 44.27 % / Description: NONE
Crystal growDetails: 0.2M AMMONIUM SULFATE, 0.1M BISTRIS PH6.5, 30% PEG 3350, 10% GLYCEROL

-
Data collection

DiffractionMean temperature: 100 K
Diffraction sourceSource: SYNCHROTRON / Site: ESRF / Beamline: ID23-1 / Wavelength: 1.07225
DetectorType: ADSC CCD / Detector: CCD
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1.07225 Å / Relative weight: 1
ReflectionResolution: 2.37→40 Å / Num. obs: 36362 / % possible obs: 99.9 % / Observed criterion σ(I): 0 / Redundancy: 7 % / Rmerge(I) obs: 0.07 / Net I/σ(I): 28.2
Reflection shellResolution: 2.37→2.41 Å / Redundancy: 6.5 % / Rmerge(I) obs: 0.45 / Mean I/σ(I) obs: 4.3 / % possible all: 100

-
Processing

Software
NameVersionClassification
REFMAC5.3.0006refinement
HKLdata reduction
SCALEPACKdata scaling
RefinementMethod to determine structure: FOURIER SYNTHESIS
Starting model: PDB ENTRY 1GNG

1gng


Resolution: 2.37→20 Å / Cor.coef. Fo:Fc: 0.948 / Cor.coef. Fo:Fc free: 0.927 / SU B: 7.152 / SU ML: 0.173 / Cross valid method: THROUGHOUT / ESU R: 0.401 / ESU R Free: 0.251 / Stereochemistry target values: MAXIMUM LIKELIHOOD / Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS.
RfactorNum. reflection% reflectionSelection details
Rfree0.24274 1830 5 %RANDOM
Rwork0.19834 ---
obs0.20062 34453 99.93 %-
Solvent computationIon probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.2 Å / Solvent model: BABINET MODEL WITH MASK
Displacement parametersBiso mean: 45.527 Å2
Baniso -1Baniso -2Baniso -3
1--0.31 Å2-0.16 Å20 Å2
2---0.31 Å20 Å2
3---0.47 Å2
Refinement stepCycle: LAST / Resolution: 2.37→20 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms5905 0 80 209 6194
Refine LS restraints
Refine-IDTypeDev idealDev ideal targetNumber
X-RAY DIFFRACTIONr_bond_refined_d0.0080.0226298
X-RAY DIFFRACTIONr_bond_other_d
X-RAY DIFFRACTIONr_angle_refined_deg1.1291.998594
X-RAY DIFFRACTIONr_angle_other_deg
X-RAY DIFFRACTIONr_dihedral_angle_1_deg5.7745770
X-RAY DIFFRACTIONr_dihedral_angle_2_deg35.60522.975279
X-RAY DIFFRACTIONr_dihedral_angle_3_deg16.244151037
X-RAY DIFFRACTIONr_dihedral_angle_4_deg19.0021552
X-RAY DIFFRACTIONr_chiral_restr0.0830.2954
X-RAY DIFFRACTIONr_gen_planes_refined0.0030.024870
X-RAY DIFFRACTIONr_gen_planes_other
X-RAY DIFFRACTIONr_nbd_refined0.1980.22881
X-RAY DIFFRACTIONr_nbd_other
X-RAY DIFFRACTIONr_nbtor_refined0.3020.24311
X-RAY DIFFRACTIONr_nbtor_other
X-RAY DIFFRACTIONr_xyhbond_nbd_refined0.130.2317
X-RAY DIFFRACTIONr_xyhbond_nbd_other
X-RAY DIFFRACTIONr_metal_ion_refined
X-RAY DIFFRACTIONr_metal_ion_other
X-RAY DIFFRACTIONr_symmetry_vdw_refined0.1960.257
X-RAY DIFFRACTIONr_symmetry_vdw_other
X-RAY DIFFRACTIONr_symmetry_hbond_refined0.1670.28
X-RAY DIFFRACTIONr_symmetry_hbond_other
X-RAY DIFFRACTIONr_symmetry_metal_ion_refined
X-RAY DIFFRACTIONr_symmetry_metal_ion_other
X-RAY DIFFRACTIONr_mcbond_it0.88323940
X-RAY DIFFRACTIONr_mcbond_other
X-RAY DIFFRACTIONr_mcangle_it1.75756251
X-RAY DIFFRACTIONr_mcangle_other
X-RAY DIFFRACTIONr_scbond_it2.31362656
X-RAY DIFFRACTIONr_scbond_other
X-RAY DIFFRACTIONr_scangle_it3.41582343
X-RAY DIFFRACTIONr_scangle_other
X-RAY DIFFRACTIONr_long_range_B_refined
X-RAY DIFFRACTIONr_long_range_B_other
X-RAY DIFFRACTIONr_rigid_bond_restr
X-RAY DIFFRACTIONr_sphericity_free
X-RAY DIFFRACTIONr_sphericity_bonded
LS refinement shellResolution: 2.37→2.431 Å / Total num. of bins used: 20
RfactorNum. reflection% reflection
Rfree0.279 133 -
Rwork0.242 2488 -
obs--99.62 %

+
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