[English] 日本語
Yorodumi
- PDB-4ez5: CDK6 (monomeric) in complex with inhibitor -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 4ez5
TitleCDK6 (monomeric) in complex with inhibitor
ComponentsCyclin-dependent kinase 6
KeywordsTRANSFERASE/TRANSFERASE INHIBITOR / Protein Kinase / ATP Binding / TRANSFERASE-TRANSFERASE INHIBITOR complex
Function / homology
Function and homology information


cyclin D2-CDK6 complex / cyclin D3-CDK6 complex / cyclin D1-CDK6 complex / cell dedifferentiation / Drug-mediated inhibition of CDK4/CDK6 activity / Evasion of Oncogene Induced Senescence Due to Defective p16INK4A binding to CDK4 and CDK6 / Evasion of Oxidative Stress Induced Senescence Due to Defective p16INK4A binding to CDK4 and CDK6 / FBXO family protein binding / lateral ventricle development / negative regulation of myeloid cell differentiation ...cyclin D2-CDK6 complex / cyclin D3-CDK6 complex / cyclin D1-CDK6 complex / cell dedifferentiation / Drug-mediated inhibition of CDK4/CDK6 activity / Evasion of Oncogene Induced Senescence Due to Defective p16INK4A binding to CDK4 and CDK6 / Evasion of Oxidative Stress Induced Senescence Due to Defective p16INK4A binding to CDK4 and CDK6 / FBXO family protein binding / lateral ventricle development / negative regulation of myeloid cell differentiation / type B pancreatic cell development / negative regulation of monocyte differentiation / astrocyte development / dentate gyrus development / regulation of hematopoietic stem cell differentiation / regulation of cell motility / gliogenesis / Regulation of RUNX1 Expression and Activity / positive regulation of cell-matrix adhesion / generation of neurons / Defective binding of RB1 mutants to E2F1,(E2F2, E2F3) / negative regulation of cellular senescence / negative regulation of cell differentiation / negative regulation of cell cycle / hematopoietic stem cell differentiation / negative regulation of osteoblast differentiation / cyclin-dependent kinase / cyclin-dependent protein serine/threonine kinase activity / cyclin-dependent protein kinase holoenzyme complex / Notch signaling pathway / ruffle / regulation of G2/M transition of mitotic cell cycle / cyclin binding / regulation of erythrocyte differentiation / response to virus / Oncogene Induced Senescence / G1/S transition of mitotic cell cycle / negative regulation of epithelial cell proliferation / Cyclin D associated events in G1 / positive regulation of fibroblast proliferation / T cell differentiation in thymus / Senescence-Associated Secretory Phenotype (SASP) / regulation of gene expression / Oxidative Stress Induced Senescence / regulation of cell cycle / protein phosphorylation / negative regulation of cell population proliferation / cell division / protein serine kinase activity / centrosome / positive regulation of gene expression / negative regulation of transcription by RNA polymerase II / signal transduction / nucleoplasm / ATP binding / nucleus / cytosol / cytoplasm
Similarity search - Function
Cyclin-dependent kinase 6 / : / 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 ...Cyclin-dependent kinase 6 / : / 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-0RS / Cyclin-dependent kinase 6
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.7 Å
AuthorsChopra, R. / Xu, M.
CitationJournal: ACS Med Chem Lett / Year: 2012
Title: Fragment-Based Discovery of 7-Azabenzimidazoles as Potent, Highly Selective, and Orally Active CDK4/6 Inhibitors.
Authors: Cho, Y.S. / Angove, H. / Brain, C. / Chen, C.H. / Cheng, H. / Cheng, R. / Chopra, R. / Chung, K. / Congreve, M. / Dagostin, C. / Davis, D.J. / Feltell, R. / Giraldes, J. / Hiscock, S.D. / ...Authors: Cho, Y.S. / Angove, H. / Brain, C. / Chen, C.H. / Cheng, H. / Cheng, R. / Chopra, R. / Chung, K. / Congreve, M. / Dagostin, C. / Davis, D.J. / Feltell, R. / Giraldes, J. / Hiscock, S.D. / Kim, S. / Kovats, S. / Lagu, B. / Lewry, K. / Loo, A. / Lu, Y. / Luzzio, M. / Maniara, W. / McMenamin, R. / Mortenson, P.N. / Benning, R. / O'Reilly, M. / Rees, D.C. / Shen, J. / Smith, T. / Wang, Y. / Williams, G. / Woolford, A.J. / Wrona, W. / Xu, M. / Yang, F. / Howard, S.
History
DepositionMay 2, 2012Deposition site: RCSB / Processing site: RCSB
Revision 1.0Feb 6, 2013Provider: repository / Type: Initial release
Revision 1.1Sep 24, 2014Group: Database references
Revision 1.2Jan 24, 2018Group: Experimental preparation / Category: exptl_crystal_grow / Item: _exptl_crystal_grow.pdbx_details
Revision 1.3Sep 13, 2023Group: Data collection / Database references ...Data collection / Database references / Derived calculations / Refinement description
Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / database_2 / pdbx_initial_refinement_model / 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_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: Cyclin-dependent kinase 6
hetero molecules


Theoretical massNumber of molelcules
Total (without water)35,4972
Polymers35,0191
Non-polymers4781
Water00
1


  • Idetical with deposited unit
  • defined by author&software
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
MethodPISA
Unit cell
Length a, b, c (Å)102.478, 102.478, 59.987
Angle α, β, γ (deg.)90.000, 90.000, 90.000
Int Tables number79
Space group name H-MI4

-
Components

#1: Protein Cyclin-dependent kinase 6 / Cell division protein kinase 6 / Serine/threonine-protein kinase PLSTIRE


Mass: 35019.215 Da / Num. of mol.: 1 / Fragment: UNP residues 1-301
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: CDK6, CDKN6 / Production host: Escherichia coli (E. coli) / References: UniProt: Q00534, cyclin-dependent kinase
#2: Chemical ChemComp-0RS / {5-[4-(dimethylamino)piperidin-1-yl]-1H-imidazo[4,5-b]pyridin-2-yl}[2-(isoquinolin-4-yl)pyridin-4-yl]methanone


Mass: 477.560 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C28H27N7O

-
Experimental details

-
Experiment

ExperimentMethod: X-RAY DIFFRACTION / Number of used crystals: 1

-
Sample preparation

CrystalDensity Matthews: 2.25 Å3/Da / Density % sol: 45.3 %
Crystal growTemperature: 298 K / Method: vapor diffusion, hanging drop / pH: 6
Details: 0.1M MES pH 6.0, 12% PEG-3350, 0.1M NH4NO3, EVAPORATION, temperature 298K, VAPOR DIFFUSION, HANGING DROP

-
Data collection

Diffraction sourceSource: SYNCHROTRON / Site: SLS / Beamline: X10SA / Wavelength: 1 Å
DetectorType: MAR CCD 165 mm / Detector: CCD
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1 Å / Relative weight: 1
ReflectionLimit h max: 37 / Limit h min: 0 / Limit k max: 37 / Limit k min: -26 / Limit l max: 22 / Limit l min: 0 / Number: 8618 / D res high: 2.7 Å / D res low: 19.625 Å / Num. obs: 8618
ReflectionResolution: 2.7→20 Å / Num. all: 8618 / Num. obs: 8618 / % possible obs: 100 % / Observed criterion σ(F): 0 / Observed criterion σ(I): 0 / Redundancy: 7.46 % / Rmerge(I) obs: 0.086 / Net I/σ(I): 9.8
Reflection scaleGroup code: 1

-
Processing

Software
NameVersionClassificationNB
d*TREK9.9.3Ldata scaling
d*TREKdata reduction
PHENIX1.7.3_928refinement
PDB_EXTRACT3.11data extraction
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 3NUP

3nup


Resolution: 2.7→19.625 Å / Occupancy max: 1 / Occupancy min: 1 / FOM work R set: 0.7125 / SU ML: 0.56 / σ(F): 1.38 / Phase error: 34.36 / Stereochemistry target values: ML
RfactorNum. reflection% reflectionSelection details
Rfree0.287 408 4.74 %RANDOM
Rwork0.2162 ---
obs0.2196 8616 99.91 %-
Solvent computationShrinkage radii: 0.98 Å / VDW probe radii: 1.2 Å / Solvent model: FLAT BULK SOLVENT MODEL / Bsol: 62.075 Å2 / ksol: 0.319 e/Å3
Displacement parametersBiso max: 156.46 Å2 / Biso mean: 93.8221 Å2 / Biso min: 61.6 Å2
Baniso -1Baniso -2Baniso -3
1-10.1464 Å20 Å2-0 Å2
2--10.1464 Å2-0 Å2
3----20.2929 Å2
Refinement stepCycle: LAST / Resolution: 2.7→19.625 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms2062 0 36 0 2098
Refine LS restraints
Refine-IDTypeDev idealNumber
X-RAY DIFFRACTIONf_bond_d0.0062148
X-RAY DIFFRACTIONf_angle_d0.9482909
X-RAY DIFFRACTIONf_chiral_restr0.061326
X-RAY DIFFRACTIONf_plane_restr0.005367
X-RAY DIFFRACTIONf_dihedral_angle_d14.314790
LS refinement shell

Refine-ID: X-RAY DIFFRACTION / Total num. of bins used: 3 / % reflection obs: 100 %

Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkNum. reflection all
2.7005-3.090.4081330.33626982831
3.09-3.8880.33671460.218627182864
3.888-19.62590.25291290.199727922921

+
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