[English] 日本語
Yorodumi
- PDB-3f88: glycogen synthase Kinase 3beta inhibitor complex -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 3f88
Titleglycogen synthase Kinase 3beta inhibitor complex
ComponentsGlycogen synthase kinase-3 beta
KeywordsTRANSFERASE / enzyme / protein kinase / inhibitor / Alternative splicing / ATP-binding / Kinase / Nucleotide-binding / Phosphoprotein / Serine/threonine-protein kinase / Wnt signaling pathway
Function / homology
Function and homology information


negative regulation of glycogen (starch) synthase activity / neuron projection organization / regulation of microtubule anchoring at centrosome / beta-catenin destruction complex disassembly / negative regulation of mesenchymal stem cell differentiation / 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 ...negative regulation of glycogen (starch) synthase activity / neuron projection organization / regulation of microtubule anchoring at centrosome / beta-catenin destruction complex disassembly / negative regulation of mesenchymal stem cell differentiation / 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 / regulation of microtubule-based process / heart valve development / 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 / 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 / regulation of neuron projection development / Constitutive Signaling by AKT1 E17K in Cancer / protein kinase A catalytic subunit binding / dynactin binding / NF-kappaB binding / canonical Wnt signaling pathway / Regulation of HSF1-mediated heat shock response / epithelial to mesenchymal transition / 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 / negative regulation of extrinsic apoptotic signaling pathway via death domain receptors / extrinsic apoptotic signaling pathway / extrinsic apoptotic signaling pathway in absence of ligand / excitatory postsynaptic potential / presynaptic modulation of chemical synaptic transmission / 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 / positive regulation of protein-containing complex assembly / 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 / Degradation of beta-catenin by the destruction complex / tau protein binding / negative regulation of canonical Wnt signaling pathway / regulation of circadian rhythm / B-WICH complex positively regulates rRNA expression / beta-catenin binding / positive regulation of GTPase activity / circadian rhythm / cellular response to amyloid-beta / positive regulation of protein catabolic process / Regulation of RUNX2 expression and activity / neuron projection development / positive regulation of proteasomal ubiquitin-dependent protein catabolic process / p53 binding / presynapse / positive regulation of protein binding / insulin receptor signaling pathway / kinase activity / postsynapse / proteasome-mediated ubiquitin-dependent protein catabolic process / peptidyl-serine phosphorylation
Similarity search - Function
Glycogen synthase kinase 3, catalytic domain / Transferase(Phosphotransferase) domain 1 / Transferase(Phosphotransferase); domain 1 / Phosphorylase Kinase; domain 1 / Phosphorylase Kinase; 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 ...Glycogen synthase kinase 3, catalytic domain / Transferase(Phosphotransferase) domain 1 / Transferase(Phosphotransferase); domain 1 / Phosphorylase Kinase; domain 1 / Phosphorylase Kinase; 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
3-methylbenzonitrile / Chem-3HT / Glycogen synthase kinase-3 beta
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / Resolution: 2.6 Å
AuthorsMol, C.D. / Dougan, D.R.
CitationJournal: Bioorg.Med.Chem. / Year: 2009
Title: Design, synthesis and structure-activity relationships of 1,3,4-oxadiazole derivatives as novel inhibitors of glycogen synthase kinase-3beta.
Authors: Saitoh, M. / Kunitomo, J. / Kimura, E. / Hayase, Y. / Kobayashi, H. / Uchiyama, N. / Kawamoto, T. / Tanaka, T. / Mol, C.D. / Dougan, D.R. / Textor, G.S. / Snell, G.P. / Itoh, F.
History
DepositionNov 11, 2008Deposition site: RCSB / Processing site: RCSB
Revision 1.0Mar 10, 2009Provider: repository / Type: Initial release
Revision 1.1Jul 13, 2011Group: Version format compliance
Revision 1.2Oct 25, 2017Group: Refinement description / Category: software
Revision 1.3Dec 27, 2023Group: Data collection / Database references / Derived calculations
Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / database_2 / struct_conn / struct_ref_seq_dif / struct_site
Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession ..._database_2.pdbx_DOI / _database_2.pdbx_database_accession / _struct_conn.pdbx_leaving_atom_flag / _struct_ref_seq_dif.details / _struct_site.pdbx_auth_asym_id / _struct_site.pdbx_auth_comp_id / _struct_site.pdbx_auth_seq_id

-
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)80,3626
Polymers79,4792
Non-polymers8834
Water2,612145
1
A: Glycogen synthase kinase-3 beta
hetero molecules


Theoretical massNumber of molelcules
Total (without water)40,1813
Polymers39,7401
Non-polymers4422
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
MethodPISA
2
B: Glycogen synthase kinase-3 beta
hetero molecules


Theoretical massNumber of molelcules
Total (without water)40,1813
Polymers39,7401
Non-polymers4422
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
MethodPISA
Unit cell
Length a, b, c (Å)66.947, 111.785, 66.955
Angle α, β, γ (deg.)90.000, 100.840, 90.000
Int Tables number4
Space group name H-MP1211

-
Components

#1: Protein Glycogen synthase kinase-3 beta / / GSK-3 beta


Mass: 39739.633 Da / Num. of mol.: 2 / Fragment: UNP residues 35-383, Protein kinase domain
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: GSK3B / Production host: Spodoptera frugiperda (fall armyworm) / Strain (production host): Hi5 / References: UniProt: P49841, tau-protein kinase
#2: Chemical ChemComp-3HT / 5-[1-(4-methoxyphenyl)-1H-benzimidazol-6-yl]-1,3,4-oxadiazole-2(3H)-thione


Mass: 324.357 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C16H12N4O2S
#3: Chemical ChemComp-2HT / 3-methylbenzonitrile


Mass: 117.148 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C8H7N
#4: Water ChemComp-HOH / water / Water


Mass: 18.015 Da / Num. of mol.: 145 / 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: 3.1 Å3/Da / Density % sol: 60.27 %
Crystal growTemperature: 277 K / Method: vapor diffusion, sitting drop / pH: 7.5
Details: 10% PEG 3350, 0.2M proline, 0.1M HEPES, pH 7.5, VAPOR DIFFUSION, SITTING DROP, temperature 277K

-
Data collection

DiffractionMean temperature: 100 K
Diffraction sourceSource: SYNCHROTRON / Site: ALS / Beamline: 5.0.3 / Wavelength: 1 Å
DetectorType: ADSC QUANTUM 315 / Detector: CCD / Date: Jul 21, 2006 / Details: mirrors
RadiationMonochromator: SAGITALLY FOCUSED Si(111) / Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1 Å / Relative weight: 1
ReflectionResolution: 2.6→20 Å / Num. obs: 29408 / % possible obs: 98.5 % / Redundancy: 3.7 % / Rmerge(I) obs: 0.044 / Χ2: 1.193 / Net I/σ(I): 32.857
Reflection shellResolution: 2.6→2.69 Å / Redundancy: 3.4 % / Rmerge(I) obs: 0.447 / Num. unique all: 2804 / Χ2: 0.769 / % possible all: 94.2

-
Processing

Software
NameVersionClassificationNB
DENZOdata reduction
SCALEPACKdata scaling
REFMAC5.2.0005refinement
PDB_EXTRACT3.006data extraction
HKL-2000data collection
AMoREphasing
RefinementResolution: 2.6→20 Å / Cor.coef. Fo:Fc: 0.96 / Cor.coef. Fo:Fc free: 0.92 / Occupancy max: 1 / Occupancy min: 0.35 / SU B: 32.423 / SU ML: 0.33 / Cross valid method: THROUGHOUT / σ(F): 0 / ESU R: 0.561 / ESU R Free: 0.338 / Stereochemistry target values: MAXIMUM LIKELIHOOD
RfactorNum. reflection% reflectionSelection details
Rfree0.281 1499 5.1 %RANDOM
Rwork0.199 ---
obs0.204 29304 98.48 %-
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 max: 158.25 Å2 / Biso mean: 75.643 Å2 / Biso min: 8 Å2
Baniso -1Baniso -2Baniso -3
1--5.19 Å20 Å2-1.01 Å2
2--10.15 Å20 Å2
3----5.34 Å2
Refine analyzeLuzzati coordinate error obs: 0 Å
Refinement stepCycle: LAST / Resolution: 2.6→20 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms5471 0 64 145 5680
Refine LS restraints
Refine-IDTypeDev idealDev ideal targetNumber
X-RAY DIFFRACTIONr_bond_refined_d0.0120.0225677
X-RAY DIFFRACTIONr_angle_refined_deg1.5831.9947725
X-RAY DIFFRACTIONr_dihedral_angle_1_deg5.8415676
X-RAY DIFFRACTIONr_dihedral_angle_2_deg37.26122.932249
X-RAY DIFFRACTIONr_dihedral_angle_3_deg19.3215940
X-RAY DIFFRACTIONr_dihedral_angle_4_deg18.5621546
X-RAY DIFFRACTIONr_chiral_restr0.0910.2859
X-RAY DIFFRACTIONr_gen_planes_refined0.0050.024312
X-RAY DIFFRACTIONr_nbd_refined0.230.22914
X-RAY DIFFRACTIONr_nbtor_refined0.3220.23847
X-RAY DIFFRACTIONr_xyhbond_nbd_refined0.1690.2257
X-RAY DIFFRACTIONr_symmetry_vdw_refined0.2470.277
X-RAY DIFFRACTIONr_symmetry_hbond_refined0.1260.24
X-RAY DIFFRACTIONr_mcbond_it3.32123492
X-RAY DIFFRACTIONr_mcangle_it4.98435599
X-RAY DIFFRACTIONr_scbond_it3.44122449
X-RAY DIFFRACTIONr_scangle_it4.56332126
LS refinement shellResolution: 2.6→2.666 Å / Total num. of bins used: 20
RfactorNum. reflection% reflection
Rfree0.403 116 -
Rwork0.345 1902 -
all-2018 -
obs--93.43 %

+
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