[English] 日本語
Yorodumi
- PDB-5oq6: Structure of CHK1 12-pt. mutant complex with aminopyrimido-benzod... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 5oq6
TitleStructure of CHK1 12-pt. mutant complex with aminopyrimido-benzodiazepinone LRRK2 inhibitor
ComponentsSerine/threonine-protein kinase Chk1
KeywordsTRANSFERASE / Parkinson's disease / Leucine-rich repeat kinase 2 / LRRK2 / Checkpoint kinase 1 / CHK1 / mutant / surrogate / kinase inhibitor
Function / homology
Function and homology information


negative regulation of G0 to G1 transition / apoptotic process involved in development / negative regulation of DNA biosynthetic process / negative regulation of mitotic nuclear division / mitotic G2/M transition checkpoint / regulation of mitotic centrosome separation / 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 / negative regulation of mitotic nuclear division / mitotic G2/M transition checkpoint / regulation of mitotic centrosome separation / 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 / 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 / G2/M DNA damage checkpoint / Signaling by SCF-KIT / 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 / DNA replication / 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 / non-specific serine/threonine protein kinase / protein kinase activity / protein phosphorylation / chromatin remodeling / protein domain specific binding / intracellular membrane-bounded organelle / protein serine kinase activity / DNA repair / protein serine/threonine kinase activity / centrosome / apoptotic process / DNA damage response / chromatin / protein-containing complex / extracellular space / nucleoplasm / ATP binding / nucleus / cytosol / cytoplasm
Similarity search - Function
Checkpoint kinase 1, catalytic domain / Phosphorylase Kinase; domain 1 / Serine/threonine-protein kinase, active site / Serine/Threonine protein kinases active-site signature. / Phosphorylase Kinase; domain 1 / Transferase(Phosphotransferase) domain 1 / Transferase(Phosphotransferase); domain 1 / Protein kinase domain / Serine/Threonine protein kinases, catalytic domain / Protein kinase, ATP binding site ...Checkpoint kinase 1, catalytic domain / Phosphorylase Kinase; domain 1 / Serine/threonine-protein kinase, active site / Serine/Threonine protein kinases active-site signature. / Phosphorylase Kinase; domain 1 / Transferase(Phosphotransferase) domain 1 / Transferase(Phosphotransferase); domain 1 / 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-4K4 / Serine/threonine-protein kinase Chk1
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 1.95 Å
AuthorsDokurno, P. / Williamson, D.S. / Acheson-Dossang, P. / Chen, I. / Murray, J.B. / Shaw, T. / Surgenor, A.E.
CitationJournal: J. Med. Chem. / Year: 2017
Title: Design of Leucine-Rich Repeat Kinase 2 (LRRK2) Inhibitors Using a Crystallographic Surrogate Derived from Checkpoint Kinase 1 (CHK1).
Authors: Williamson, D.S. / Smith, G.P. / Acheson-Dossang, P. / Bedford, S.T. / Chell, V. / Chen, I.J. / Daechsel, J.C.A. / Daniels, Z. / David, L. / Dokurno, P. / Hentzer, M. / Herzig, M.C. / ...Authors: Williamson, D.S. / Smith, G.P. / Acheson-Dossang, P. / Bedford, S.T. / Chell, V. / Chen, I.J. / Daechsel, J.C.A. / Daniels, Z. / David, L. / Dokurno, P. / Hentzer, M. / Herzig, M.C. / Hubbard, R.E. / Moore, J.D. / Murray, J.B. / Newland, S. / Ray, S.C. / Shaw, T. / Surgenor, A.E. / Terry, L. / Thirstrup, K. / Wang, Y. / Christensen, K.V.
History
DepositionAug 10, 2017Deposition site: PDBE / Processing site: PDBE
Revision 1.0Oct 25, 2017Provider: repository / Type: Initial release
Revision 1.1Nov 22, 2017Group: 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

-
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)34,7003
Polymers34,0941
Non-polymers6062
Water2,972165
1


  • Idetical with deposited unit
  • defined by author&software
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area150 Å2
ΔGint-10 kcal/mol
Surface area12650 Å2
MethodPISA
Unit cell
Length a, b, c (Å)45.000, 66.160, 54.980
Angle α, β, γ (deg.)90.000, 101.840, 90.000
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
Mutation: A19S, Y20F, N59L, V68I, L84M, Y86L, C87A, E91S, E134H, S147A, F149Y, G150S
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: CHEK1, CHK1 / Plasmid: Pfastbac1 / Cell line (production host): SF9 / Production host: Spodoptera frugiperda (fall armyworm)
References: UniProt: O14757, non-specific serine/threonine protein kinase
#2: Chemical ChemComp-4K4 / 2-[(2-methoxy-4-{[4-(4-methylpiperazin-1-yl)piperidin-1-yl]carbonyl}phenyl)amino]-5,11-dimethyl-5,11-dihydro-6H-pyrimido[4,5-b][1,4]benzodiazepin-6-one


Mass: 570.685 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C31H38N8O3 / Feature type: SUBJECT OF INVESTIGATION
#3: Chemical ChemComp-CL / CHLORIDE ION


Mass: 35.453 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: Cl
#4: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 165 / 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: 2.35 Å3/Da / Density % sol: 47.65 %
Crystal growTemperature: 293 K / Method: vapor diffusion, sitting drop / pH: 6.5
Details: 7% PEG 8000, 0.1 M MES buffer pH 6.5, 20% ethylene glycol

-
Data collection

DiffractionMean temperature: 100 K
Diffraction sourceSource: SYNCHROTRON / Site: Diamond / Beamline: I03 / Wavelength: 0.9763 Å
DetectorType: DECTRIS PILATUS3 6M / Detector: PIXEL / Date: Sep 20, 2012
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.9763 Å / Relative weight: 1
ReflectionResolution: 1.91→44.04 Å / Num. obs: 24224 / % possible obs: 98.5 % / Redundancy: 2.9 % / CC1/2: 0.998 / Rmerge(I) obs: 0.051 / Rpim(I) all: 0.036 / Rrim(I) all: 0.063 / Net I/σ(I): 13.7 / Num. measured all: 70334 / Scaling rejects: 0
Reflection shell

Diffraction-ID: 1

Resolution (Å)Redundancy (%)Rmerge(I) obsNum. unique obsCC1/2Rpim(I) allRrim(I) all% possible all
1.91-1.962.60.55517770.7730.4130.69598.2
8.54-44.042.70.0182690.9990.0120.02289.6

-
Processing

Software
NameVersionClassification
Aimless0.1.16data scaling
REFMAC5.8.0158refinement
PDB_EXTRACT3.22data extraction
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 5OOT

5oot


Resolution: 1.95→30 Å / Cor.coef. Fo:Fc: 0.973 / Cor.coef. Fo:Fc free: 0.959 / SU B: 3.97 / SU ML: 0.105 / SU R Cruickshank DPI: 0.1345 / Cross valid method: THROUGHOUT / σ(F): 0 / ESU R: 0.134 / ESU R Free: 0.124
Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS U VALUES : REFINED INDIVIDUALLY
RfactorNum. reflection% reflectionSelection details
Rfree0.1918 1164 5.1 %RANDOM
Rwork0.1578 ---
obs0.1597 21610 98.48 %-
Solvent computationIon probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.2 Å
Displacement parametersBiso max: 117.91 Å2 / Biso mean: 40.027 Å2 / Biso min: 16.98 Å2
Baniso -1Baniso -2Baniso -3
1--2.47 Å20 Å2-1.05 Å2
2---0.79 Å2-0 Å2
3---3.4 Å2
Refinement stepCycle: final / Resolution: 1.95→30 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms2071 0 43 165 2279
Biso mean--47.46 44.84 -
Num. residues----257
Refine LS restraints
Refine-IDTypeDev idealDev ideal targetNumber
X-RAY DIFFRACTIONr_bond_refined_d0.0190.0192167
X-RAY DIFFRACTIONr_bond_other_d0.0020.022026
X-RAY DIFFRACTIONr_angle_refined_deg1.9491.9852941
X-RAY DIFFRACTIONr_angle_other_deg1.1233.0024652
X-RAY DIFFRACTIONr_dihedral_angle_1_deg5.6845255
X-RAY DIFFRACTIONr_dihedral_angle_2_deg35.96324.3100
X-RAY DIFFRACTIONr_dihedral_angle_3_deg18.41715375
X-RAY DIFFRACTIONr_dihedral_angle_4_deg19.2861513
X-RAY DIFFRACTIONr_chiral_restr0.130.2315
X-RAY DIFFRACTIONr_gen_planes_refined0.010.0212368
X-RAY DIFFRACTIONr_gen_planes_other0.0020.02422
LS refinement shellResolution: 1.95→2.055 Å / Rfactor Rfree error: 0 / Total num. of bins used: 10
RfactorNum. reflection% reflection
Rfree0.265 170 -
Rwork0.269 3146 -
all-3316 -
obs--99.04 %

+
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