[English] 日本語
Yorodumi
- PDB-2yex: Synthesis and evaluation of triazolones as checkpoint kinase 1 in... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 2yex
TitleSynthesis and evaluation of triazolones as checkpoint kinase 1 inhibitors
ComponentsSERINE/THREONINE-PROTEIN KINASE CHK1
KeywordsTRANSFERASE / CELL CYCLE / CHK
Function / homology
Function and homology information


negative regulation of G0 to G1 transition / apoptotic process involved in development / histone H3T11 kinase activity / negative regulation of DNA biosynthetic process / mitotic G2/M transition checkpoint / negative regulation of mitotic nuclear division / regulation of mitotic centrosome separation / inner cell mass cell proliferation / regulation of double-strand break repair via homologous recombination / nucleus organization ...negative regulation of G0 to G1 transition / apoptotic process involved in development / histone H3T11 kinase activity / negative regulation of DNA biosynthetic process / mitotic G2/M transition checkpoint / negative regulation of mitotic nuclear division / regulation of mitotic centrosome separation / inner cell mass cell proliferation / regulation of double-strand break repair via homologous recombination / nucleus organization / negative regulation of gene expression, epigenetic / cellular response to caffeine / Transcriptional Regulation by E2F6 / mitotic G2 DNA damage checkpoint signaling / Presynaptic phase of homologous DNA pairing and strand exchange / replicative senescence / signal transduction in response to DNA damage / positive regulation of cell cycle / Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex / Activation of ATR in response to replication stress / DNA damage checkpoint signaling / regulation of signal transduction by p53 class mediator / condensed nuclear chromosome / replication fork / TP53 Regulates Transcription of DNA Repair Genes / peptidyl-threonine phosphorylation / Ubiquitin Mediated Degradation of Phosphorylated Cdc25A / Signaling by SCF-KIT / G2/M DNA damage checkpoint / cellular response to mechanical stimulus / G2/M transition of mitotic cell cycle / regulation of cell population proliferation / Processing of DNA double-strand break ends / Regulation of TP53 Activity through Phosphorylation / DNA replication / non-specific serine/threonine protein kinase / protein kinase activity / chromatin remodeling / protein phosphorylation / protein domain specific binding / intracellular membrane-bounded organelle / protein serine kinase activity / DNA repair / protein serine/threonine kinase activity / centrosome / DNA damage response / chromatin / apoptotic process / protein-containing complex / extracellular space / nucleoplasm / ATP binding / nucleus / cytosol / cytoplasm
Similarity search - Function
Checkpoint kinase 1, 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 ...Checkpoint kinase 1, 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
Chem-YEX / Serine/threonine-protein kinase Chk1
Similarity search - Component
Biological speciesHOMO SAPIENS (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 1.3 Å
AuthorsRead, J.A. / Breed, J. / Haye, H. / McCall, E. / Vallentine, A. / White, A.
Citation
Journal: Bioorg.Med.Chem.Lett. / Year: 2012
Title: Synthesis and Evaluation of Triazolones as Checkpoint Kinase 1 Inhibitors.
Authors: Oza, V. / Ashwell, S. / Brassil, P. / Breed, J. / Ezhuthachan, J. / Deng, C. / Grondine, M. / Horn, C. / Liu, D. / Lyne, P. / Newcombe, N. / Pass, M. / Read, J. / Su, M. / Toader, D. / Yu, D. ...Authors: Oza, V. / Ashwell, S. / Brassil, P. / Breed, J. / Ezhuthachan, J. / Deng, C. / Grondine, M. / Horn, C. / Liu, D. / Lyne, P. / Newcombe, N. / Pass, M. / Read, J. / Su, M. / Toader, D. / Yu, D. / Yu, Y. / Zabludoff, S.
#1: Journal: Bioorg.Med.Chem.Lett. / Year: 2010
Title: Discovery of a Novel Class of Triazolones as Checkpoint Kinase Inhibitors--Hit to Lead Exploration.
Authors: Oza, V. / Ashwell, S. / Brassil, P. / Breed, J. / Deng, C. / Ezhuthachan, J. / Haye, H. / Horn, C. / Janetka, J. / Lyne, P. / Newcombe, N. / Otterbien, L. / Pass, M. / Read, J. / Roswell, S. ...Authors: Oza, V. / Ashwell, S. / Brassil, P. / Breed, J. / Deng, C. / Ezhuthachan, J. / Haye, H. / Horn, C. / Janetka, J. / Lyne, P. / Newcombe, N. / Otterbien, L. / Pass, M. / Read, J. / Roswell, S. / Su, M. / Toader, D. / Yu, D. / Yu, Y. / Valentine, A. / Webborn, P. / White, A. / Zabludoff, S. / Zheng, X.
History
DepositionMar 31, 2011Deposition site: PDBE / Processing site: PDBE
Revision 1.0Mar 14, 2012Provider: repository / Type: Initial release
Revision 1.1May 8, 2024Group: Data collection / Database references ...Data collection / Database references / Derived calculations / Other
Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / database_2 / pdbx_database_status / 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_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: SERINE/THREONINE-PROTEIN KINASE CHK1
hetero molecules


Theoretical massNumber of molelcules
Total (without water)32,84610
Polymers31,8411
Non-polymers1,0059
Water8,071448
1


  • Idetical with deposited unit
  • defined by author&software
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
MethodPISA
Unit cell
Length a, b, c (Å)41.352, 70.770, 104.327
Angle α, β, γ (deg.)90.00, 90.00, 90.00
Int Tables number19
Space group name H-MP212121

-
Components

#1: Protein SERINE/THREONINE-PROTEIN KINASE CHK1 / CHK1 CHECKPOINT KINASE


Mass: 31840.738 Da / Num. of mol.: 1 / Fragment: CHK1KD, RESIDUES 1-276
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) HOMO SAPIENS (human) / Production host: SPODOPTERA FRUGIPERDA (fall armyworm) / Strain (production host): SF9
References: UniProt: O14757, non-specific serine/threonine protein kinase
#2: Chemical
ChemComp-GOL / GLYCEROL / GLYCERIN / PROPANE-1,2,3-TRIOL


Mass: 92.094 Da / Num. of mol.: 7 / Source method: obtained synthetically / Formula: C3H8O3
#3: Chemical ChemComp-YEX / 5-METHYL-8-(1H-PYRROL-2-YL)[1,2,4]TRIAZOLO[4,3-A]QUINOLIN-1(2H)-ONE


Mass: 264.282 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C15H12N4O
#4: Chemical ChemComp-SO4 / SULFATE ION


Mass: 96.063 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: SO4
#5: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 448 / 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: 2.46 Å3/Da / Density % sol: 50 % / Description: NONE
Crystal growpH: 7.5 / Details: pH 7.5

-
Data collection

DiffractionMean temperature: 100 K
Diffraction sourceSource: SYNCHROTRON / Site: ESRF / Beamline: ID29 / Wavelength: 1.265
DetectorType: ADSC QUANTUM 315r / Detector: CCD / Date: Apr 10, 2003 / Details: MIRRORS
RadiationMonochromator: SI111 / Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1.265 Å / Relative weight: 1
ReflectionResolution: 1.3→25 Å / Num. obs: 62083 / % possible obs: 83.6 % / Observed criterion σ(I): 2 / Redundancy: 2.8 % / Biso Wilson estimate: 11.2 Å2 / Rmerge(I) obs: 0.06 / Net I/σ(I): 13.3
Reflection shellResolution: 1.3→1.37 Å / Redundancy: 1.7 % / Rmerge(I) obs: 0.52 / Mean I/σ(I) obs: 1.7 / % possible all: 34.3

-
Processing

Software
NameVersionClassification
REFMAC5.5.0110refinement
MOSFLMdata reduction
SCALAdata scaling
AMoREphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT / Resolution: 1.3→24.92 Å / Cor.coef. Fo:Fc: 0.973 / Cor.coef. Fo:Fc free: 0.962 / SU B: 1.359 / SU ML: 0.026 / Cross valid method: THROUGHOUT / ESU R: 0.053 / ESU R Free: 0.05 / Stereochemistry target values: MAXIMUM LIKELIHOOD / Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS.
RfactorNum. reflection% reflectionSelection details
Rfree0.16415 3143 5.1 %RANDOM
Rwork0.13352 ---
obs0.13503 58940 81.59 %-
Solvent computationIon probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.4 Å / Solvent model: BABINET MODEL WITH MASK
Displacement parametersBiso mean: 8.814 Å2
Baniso -1Baniso -2Baniso -3
1--0.42 Å20 Å20 Å2
2--0.74 Å20 Å2
3----0.33 Å2
Refinement stepCycle: LAST / Resolution: 1.3→24.92 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms2151 0 67 448 2666
Refine LS restraints
Refine-IDTypeDev idealDev ideal targetNumber
X-RAY DIFFRACTIONr_bond_refined_d0.0110.0222306
X-RAY DIFFRACTIONr_bond_other_d0.0020.021581
X-RAY DIFFRACTIONr_angle_refined_deg1.5071.9883134
X-RAY DIFFRACTIONr_angle_other_deg0.93433861
X-RAY DIFFRACTIONr_dihedral_angle_1_deg5.3835282
X-RAY DIFFRACTIONr_dihedral_angle_2_deg35.93124.667105
X-RAY DIFFRACTIONr_dihedral_angle_3_deg9.92215387
X-RAY DIFFRACTIONr_dihedral_angle_4_deg14.6261512
X-RAY DIFFRACTIONr_chiral_restr0.0880.2334
X-RAY DIFFRACTIONr_gen_planes_refined0.0080.0212570
X-RAY DIFFRACTIONr_gen_planes_other0.0010.02455
X-RAY DIFFRACTIONr_nbd_refined
X-RAY DIFFRACTIONr_nbd_other
X-RAY DIFFRACTIONr_nbtor_refined
X-RAY DIFFRACTIONr_nbtor_other
X-RAY DIFFRACTIONr_xyhbond_nbd_refined
X-RAY DIFFRACTIONr_xyhbond_nbd_other
X-RAY DIFFRACTIONr_metal_ion_refined
X-RAY DIFFRACTIONr_metal_ion_other
X-RAY DIFFRACTIONr_symmetry_vdw_refined
X-RAY DIFFRACTIONr_symmetry_vdw_other
X-RAY DIFFRACTIONr_symmetry_hbond_refined
X-RAY DIFFRACTIONr_symmetry_hbond_other
X-RAY DIFFRACTIONr_symmetry_metal_ion_refined
X-RAY DIFFRACTIONr_symmetry_metal_ion_other
X-RAY DIFFRACTIONr_mcbond_it1.1441.51375
X-RAY DIFFRACTIONr_mcbond_other0.4391.5546
X-RAY DIFFRACTIONr_mcangle_it1.77622231
X-RAY DIFFRACTIONr_mcangle_other
X-RAY DIFFRACTIONr_scbond_it2.633931
X-RAY DIFFRACTIONr_scbond_other
X-RAY DIFFRACTIONr_scangle_it3.7954.5899
X-RAY DIFFRACTIONr_scangle_other
X-RAY DIFFRACTIONr_long_range_B_refined
X-RAY DIFFRACTIONr_long_range_B_other
X-RAY DIFFRACTIONr_rigid_bond_restr1.15933887
X-RAY DIFFRACTIONr_sphericity_free5.5783449
X-RAY DIFFRACTIONr_sphericity_bonded2.29433832
LS refinement shellResolution: 1.3→1.334 Å / Total num. of bins used: 20
RfactorNum. reflection% reflection
Rfree0.292 78 -
Rwork0.211 1458 -
obs--27.76 %
Refinement TLS params.Method: refined / Origin x: 14.0183 Å / Origin y: 34.4825 Å / Origin z: 16.5371 Å
111213212223313233
T0.0096 Å20.0011 Å20.0055 Å2-0.0004 Å20.0008 Å2--0.0082 Å2
L0.2212 °20.0183 °20.0732 °2-0.0522 °2-0.0135 °2--0.1886 °2
S-0.0033 Å °0.0018 Å °0.0069 Å °0.0044 Å °0.0021 Å °-0.0027 Å °-0.0104 Å °-0.0062 Å °0.0012 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