[English] 日本語
Yorodumi
- PDB-6hk3: Crystal structure of GSK-3B in complex with pyrazine inhibitor C44 -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 6hk3
TitleCrystal structure of GSK-3B in complex with pyrazine inhibitor C44
Components
  • GLY-SER-HIS-GLY-HIS-HIS-HIS-HIS
  • Glycogen synthase kinase-3 beta
KeywordsTRANSFERASE / GSK 3B / Complex / pyrazine / inhibitor
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 mitochondrial outer membrane permeabilization involved in apoptotic signaling pathway / positive regulation of cilium assembly / beta-catenin destruction complex / APC truncation mutants have impaired AXIN binding / AXIN missense mutants destabilize the destruction complex / Truncations of AMER1 destabilize the destruction complex / CRMPs in Sema3A signaling / heart valve development / tau-protein kinase / 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 / regulation of long-term synaptic potentiation / Wnt signalosome / 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 / G protein-coupled dopamine receptor signaling pathway / negative regulation of epithelial to mesenchymal transition / tau-protein kinase activity / positive regulation of cell-matrix adhesion / regulation of axonogenesis / regulation of dendrite morphogenesis / ER overload response / glycogen metabolic process / regulation of neuron projection development / establishment of cell polarity / protein kinase A catalytic subunit binding / Constitutive Signaling by AKT1 E17K in Cancer / dynactin binding / Regulation of HSF1-mediated heat shock response / negative regulation of osteoblast differentiation / epithelial to mesenchymal transition / canonical Wnt signaling pathway / NF-kappaB 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 in absence of ligand / cellular response to retinoic acid / extrinsic apoptotic signaling pathway / positive regulation of autophagy / presynaptic modulation of chemical synaptic transmission / Transcriptional and post-translational regulation of MITF-M expression and activity / regulation of microtubule cytoskeleton organization / response to endoplasmic reticulum stress / negative regulation of cell migration / hippocampus development / positive regulation of protein export from nucleus / positive regulation of protein ubiquitination / excitatory postsynaptic potential / mitochondrion organization / Ubiquitin-dependent degradation of Cyclin D / 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 / regulation of circadian rhythm / beta-catenin binding / Degradation of beta-catenin by the destruction complex / B-WICH complex positively regulates rRNA expression / tau protein binding / Wnt signaling pathway / circadian rhythm / cellular response to amyloid-beta / positive regulation of protein catabolic process / neuron projection development / Regulation of RUNX2 expression and activity / kinase activity / positive regulation of protein binding / p53 binding / positive regulation of neuron apoptotic process / insulin receptor signaling pathway / positive regulation of proteasomal ubiquitin-dependent protein catabolic process / presynapse
Similarity search - Function
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 ...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
Chem-G8B / MALONATE ION / Glycogen synthase kinase-3 beta
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.35 Å
AuthorsPiretti, V. / Giabbai, B. / Demitri, N. / Di Martino, R. / Tripathi, S.K. / Gobbo, D. / Decherchi, S. / Storici, P. / Girotto, S. / Cavalli, A.
CitationJournal: J Chem Theory Comput / Year: 2019
Title: Investigating Drug-Target Residence Time in Kinases through Enhanced Sampling Simulations.
Authors: Gobbo, D. / Piretti, V. / Di Martino, R.M.C. / Tripathi, S.K. / Giabbai, B. / Storici, P. / Demitri, N. / Girotto, S. / Decherchi, S. / Cavalli, A.
History
DepositionSep 5, 2018Deposition site: PDBE / Processing site: PDBE
Revision 1.0Jul 17, 2019Provider: repository / Type: Initial release
Revision 1.1Aug 21, 2019Group: Data collection / Database references / Category: citation
Item: _citation.journal_volume / _citation.page_first / _citation.page_last
Revision 1.2Jan 17, 2024Group: 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
Revision 1.3Oct 23, 2024Group: Structure summary / Category: pdbx_entry_details / pdbx_modification_feature

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Glycogen synthase kinase-3 beta
B: Glycogen synthase kinase-3 beta
N: GLY-SER-HIS-GLY-HIS-HIS-HIS-HIS
hetero molecules


Theoretical massNumber of molelcules
Total (without water)82,44015
Polymers80,6753
Non-polymers1,76512
Water3,387188
1
A: Glycogen synthase kinase-3 beta
hetero molecules


Theoretical massNumber of molelcules
Total (without water)40,8578
Polymers39,8831
Non-polymers9747
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area960 Å2
ΔGint-6 kcal/mol
Surface area16630 Å2
MethodPISA
2
B: Glycogen synthase kinase-3 beta
hetero molecules

N: GLY-SER-HIS-GLY-HIS-HIS-HIS-HIS


Theoretical massNumber of molelcules
Total (without water)41,5837
Polymers40,7932
Non-polymers7905
Water362
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
crystal symmetry operation1_655x+1,y,z1
Buried area1680 Å2
ΔGint-9 kcal/mol
Surface area17170 Å2
MethodPISA
Unit cell
Length a, b, c (Å)64.318, 67.117, 67.238
Angle α, β, γ (deg.)79.840, 76.210, 89.630
Int Tables number1
Space group name H-MP1

-
Components

-
Protein / Protein/peptide , 2 types, 3 molecules ABN

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


Mass: 39882.773 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: Protein/peptide GLY-SER-HIS-GLY-HIS-HIS-HIS-HIS


Mass: 909.931 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Production host: Trichoplusia ni (cabbage looper)

-
Non-polymers , 6 types, 200 molecules

#3: Chemical ChemComp-G8B / 3-azanyl-~{N}-(2-methoxyphenyl)-6-[4-(4-methylpiperazin-1-yl)sulfonylphenyl]pyrazine-2-carboxamide


Mass: 482.555 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C23H26N6O4S / Feature type: SUBJECT OF INVESTIGATION
#4: Chemical ChemComp-MLI / MALONATE ION


Mass: 102.046 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C3H2O4
#5: Chemical
ChemComp-GOL / GLYCEROL / GLYCERIN / PROPANE-1,2,3-TRIOL


Mass: 92.094 Da / Num. of mol.: 4 / Source method: obtained synthetically / Formula: C3H8O3
#6: Chemical ChemComp-CL / CHLORIDE ION


Mass: 35.453 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: Cl
#7: Chemical ChemComp-DMS / DIMETHYL SULFOXIDE


Mass: 78.133 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C2H6OS / Comment: DMSO, precipitant*YM
#8: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 188 / 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: 3.44 Å3/Da / Density % sol: 64.21 %
Crystal growTemperature: 293 K / Method: vapor diffusion, sitting drop / pH: 7.4 / Details: 0.2M potassium fluoride 22% PEG 3350

-
Data collection

DiffractionMean temperature: 100 K
Diffraction sourceSource: SYNCHROTRON / Site: ELETTRA / Beamline: 5.2R / Wavelength: 1 Å
DetectorType: DECTRIS PILATUS 2M / Detector: PIXEL / Date: Mar 20, 2018
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1 Å / Relative weight: 1
ReflectionResolution: 2.3→46.22 Å / Num. obs: 46585 / % possible obs: 97.1 % / Redundancy: 2.4 % / CC1/2: 0.994 / Rmerge(I) obs: 0.098 / Rpim(I) all: 0.077 / Rrim(I) all: 0.125 / Net I/σ(I): 5.2 / Num. measured all: 113743 / Scaling rejects: 2
Reflection shell

Diffraction-ID: 1

Resolution (Å)Redundancy (%)Rmerge(I) obsNum. measured allNum. unique obsCC1/2Rpim(I) allRrim(I) allNet I/σ(I) obs% possible all
2.3-2.382.51.4541052342280.3411.1171.8440.589.5
8.89-46.222.60.03820778140.9950.0290.04818.798.2

-
Processing

Software
NameVersionClassification
REFMACrefinement
Aimless0.6.2data scaling
PDB_EXTRACT3.24data extraction
XDSdata reduction
PHASERphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 4ACD

4acd


Resolution: 2.35→42.977 Å / SU ML: 0.35 / Cross valid method: THROUGHOUT / σ(F): 1.96 / Phase error: 26.45 / Stereochemistry target values: ML
RfactorNum. reflection% reflection
Rfree0.2335 2182 4.99 %
Rwork0.2041 --
obs0.2056 43734 97.69 %
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT BULK SOLVENT MODEL
Displacement parametersBiso max: 136.69 Å2 / Biso mean: 56.4885 Å2 / Biso min: 18.99 Å2
Refinement stepCycle: final / Resolution: 2.35→42.977 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms5572 0 116 192 5880
Biso mean--49.89 55.1 -
Num. residues----708

+
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