[English] 日本語
Yorodumi
- PDB-8siv: Structure of Compound 2 bound to the CHK1 10-point mutant -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 8siv
TitleStructure of Compound 2 bound to the CHK1 10-point mutant
ComponentsSerine/threonine-protein kinase Chk1
KeywordsTRANSFERASE / LRRK2 / Parkinson's / kinase
Function / homology
Function and homology information


negative regulation of G0 to G1 transition / apoptotic process involved in development / negative regulation of DNA biosynthetic process / regulation of mitotic centrosome separation / negative regulation of mitotic nuclear division / mitotic G2/M transition checkpoint / inner cell mass cell proliferation / regulation of double-strand break repair via homologous recombination / negative regulation of gene expression, epigenetic / nucleus organization ...negative regulation of G0 to G1 transition / apoptotic process involved in development / negative regulation of DNA biosynthetic process / regulation of mitotic centrosome separation / negative regulation of mitotic nuclear division / mitotic G2/M transition checkpoint / inner cell mass cell proliferation / regulation of double-strand break repair via homologous recombination / negative regulation of gene expression, epigenetic / nucleus organization / cellular response to caffeine / mitotic G2 DNA damage checkpoint signaling / Transcriptional Regulation by E2F6 / Presynaptic phase of homologous DNA pairing and strand exchange / replicative senescence / signal transduction in response to DNA damage / Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex / Activation of ATR in response to replication stress / positive regulation of cell cycle / peptidyl-threonine phosphorylation / DNA damage checkpoint signaling / condensed nuclear chromosome / regulation of signal transduction by p53 class mediator / replication fork / TP53 Regulates Transcription of DNA Repair Genes / 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 / eukaryotic translation initiation factor 2alpha kinase activity / 3-phosphoinositide-dependent protein kinase activity / DNA-dependent protein kinase activity / ribosomal protein S6 kinase activity / histone H3S10 kinase activity / histone H2AXS139 kinase activity / histone H3S28 kinase activity / histone H4S1 kinase activity / histone H2BS14 kinase activity / histone H3T3 kinase activity / histone H2AS121 kinase activity / Rho-dependent protein serine/threonine kinase activity / histone H2BS36 kinase activity / histone H3S57 kinase activity / histone H2AT120 kinase activity / AMP-activated protein kinase activity / histone H2AS1 kinase activity / histone H3T6 kinase activity / histone H3T11 kinase activity / histone H3T45 kinase activity / DNA replication / non-specific serine/threonine protein kinase / protein kinase activity / protein phosphorylation / chromatin remodeling / protein domain specific binding / protein serine kinase activity / DNA repair / protein serine/threonine kinase activity / intracellular membrane-bounded organelle / apoptotic process / centrosome / DNA damage response / chromatin / protein-containing complex / extracellular space / nucleoplasm / ATP binding / nucleus / cytosol / cytoplasm
Similarity search - Function
Checkpoint kinase 1, 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-ZXH / Serine/threonine-protein kinase Chk1
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 1.759 Å
AuthorsPalte, R.L.
Funding support1items
OrganizationGrant numberCountry
Not funded
CitationJournal: J.Med.Chem. / Year: 2023
Title: Discovery of MK-1468: A Potent, Kinome-Selective, Brain-Penetrant Amidoisoquinoline LRRK2 Inhibitor for the Potential Treatment of Parkinson's Disease.
Authors: Kattar, S.D. / Gulati, A. / Margrey, K.A. / Keylor, M.H. / Ardolino, M. / Yan, X. / Johnson, R. / Palte, R.L. / McMinn, S.E. / Nogle, L. / Su, J. / Xiao, D. / Piesvaux, J. / Lee, S. / Hegde, ...Authors: Kattar, S.D. / Gulati, A. / Margrey, K.A. / Keylor, M.H. / Ardolino, M. / Yan, X. / Johnson, R. / Palte, R.L. / McMinn, S.E. / Nogle, L. / Su, J. / Xiao, D. / Piesvaux, J. / Lee, S. / Hegde, L.G. / Woodhouse, J.D. / Faltus, R. / Moy, L.Y. / Xiong, T. / Ciaccio, P.J. / Pearson, K. / Patel, M. / Otte, K.M. / Leyns, C.E.G. / Kennedy, M.E. / Bennett, D.J. / DiMauro, E.F. / Fell, M.J. / Fuller, P.H.
History
DepositionApr 17, 2023Deposition site: RCSB / Processing site: RCSB
Revision 1.0Nov 1, 2023Provider: repository / Type: Initial release
Revision 1.1Nov 15, 2023Group: Database references / Category: citation
Item: _citation.journal_volume / _citation.page_first / _citation.page_last

-
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)34,5242
Polymers34,0941
Non-polymers4301
Water2,684149
1


  • Idetical with deposited unit
  • defined by author&software
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
MethodPISA
Unit cell
Length a, b, c (Å)44.827, 65.330, 54.139
Angle α, β, γ (deg.)90.00, 101.86, 90.00
Int Tables number4
Space group name H-MP1211

-
Components

#1: Protein Serine/threonine-protein kinase Chk1 / CHK1 checkpoint homolog / Cell cycle checkpoint kinase / Checkpoint kinase-1


Mass: 34094.207 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: CHEK1, CHK1 / Production host: Spodoptera frugiperda (fall armyworm)
References: UniProt: O14757, non-specific serine/threonine protein kinase
#2: Chemical ChemComp-ZXH / N-(7-chloro-6-{1-[(3R,4R)-4-hydroxy-3-methyloxolan-3-yl]piperidin-4-yl}isoquinolin-3-yl)cyclopropanecarboxamide


Mass: 429.940 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C23H28ClN3O3 / Feature type: SUBJECT OF INVESTIGATION
#3: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 149 / 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: 2.28 Å3/Da / Density % sol: 45.95 %
Crystal growTemperature: 293 K / Method: vapor diffusion, sitting drop / pH: 6.5
Details: 11% PEG 8000, 15-20% ethylene glycol, 0.1 M MES (pH 6.5), 5% 6-aminohexanoic acid

-
Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: APS / Beamline: 17-ID / Wavelength: 1 Å
DetectorType: DECTRIS PILATUS 6M / Detector: PIXEL / Date: Dec 17, 2021
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1 Å / Relative weight: 1
ReflectionResolution: 1.759→41.151 Å / Num. obs: 18990 / % possible obs: 90.6 % / Redundancy: 3.4 % / CC1/2: 0.996 / Net I/σ(I): 7.4
Reflection shellResolution: 1.759→2.002 Å / Num. unique obs: 949 / CC1/2: 0.642

-
Processing

Software
NameVersionClassification
autoBUSTER2.11.8 (20-OCT-2021)refinement
Aimlessdata scaling
PDB_EXTRACTdata extraction
BUSTERphasing
autoPROCdata processing
XDSdata reduction
RefinementMethod to determine structure: MOLECULAR REPLACEMENT / Resolution: 1.759→41.15 Å / Cor.coef. Fo:Fc: 0.935 / Cor.coef. Fo:Fc free: 0.912 / SU R Cruickshank DPI: 0.207 / Cross valid method: THROUGHOUT / σ(F): 0 / SU R Blow DPI: 0.209 / SU Rfree Blow DPI: 0.178 / SU Rfree Cruickshank DPI: 0.179
RfactorNum. reflection% reflectionSelection details
Rfree0.2512 929 4.89 %RANDOM
Rwork0.2097 ---
obs0.2117 18990 62.3 %-
Displacement parametersBiso mean: 30.16 Å2
Baniso -1Baniso -2Baniso -3
1-2.2571 Å20 Å2-0.3787 Å2
2---0.2036 Å20 Å2
3----2.0535 Å2
Refine analyzeLuzzati coordinate error obs: 0.29 Å
Refinement stepCycle: LAST / Resolution: 1.759→41.15 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms2098 0 30 149 2277
Refine LS restraints
Refine-IDTypeDev idealNumberRestraint functionWeight
X-RAY DIFFRACTIONt_bond_d0.0082183HARMONIC2
X-RAY DIFFRACTIONt_angle_deg0.932960HARMONIC2
X-RAY DIFFRACTIONt_dihedral_angle_d768SINUSOIDAL2
X-RAY DIFFRACTIONt_incorr_chiral_ct
X-RAY DIFFRACTIONt_pseud_angle
X-RAY DIFFRACTIONt_trig_c_planes
X-RAY DIFFRACTIONt_gen_planes378HARMONIC5
X-RAY DIFFRACTIONt_it2183HARMONIC10
X-RAY DIFFRACTIONt_nbd
X-RAY DIFFRACTIONt_omega_torsion2.96
X-RAY DIFFRACTIONt_other_torsion16.49
X-RAY DIFFRACTIONt_improper_torsion
X-RAY DIFFRACTIONt_chiral_improper_torsion269SEMIHARMONIC5
X-RAY DIFFRACTIONt_sum_occupancies
X-RAY DIFFRACTIONt_utility_distance
X-RAY DIFFRACTIONt_utility_angle
X-RAY DIFFRACTIONt_utility_torsion
X-RAY DIFFRACTIONt_ideal_dist_contact1828SEMIHARMONIC4
LS refinement shellResolution: 1.76→1.93 Å / Total num. of bins used: 47
RfactorNum. reflection% reflection
Rfree0.245 -5.57 %
Rwork0.2742 390 -
all0.2728 413 -
obs--5.57 %

+
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