[English] 日本語
Yorodumi
- PDB-6qtg: Crystal structure of human CDK8/CYCC in complex with BI-1347 -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 6qtg
TitleCrystal structure of human CDK8/CYCC in complex with BI-1347
Components
  • Cyclin-C
  • Cyclin-dependent kinase 8
KeywordsCELL CYCLE / Inhibitor / Complex
Function / homology
Function and homology information


CKM complex / G0 to G1 transition / negative regulation of triglyceride metabolic process / mediator complex / Generic Transcription Pathway / [RNA-polymerase]-subunit kinase / cyclin-dependent protein serine/threonine kinase regulator activity / negative regulation of Notch signaling pathway / RSV-host interactions / cyclin-dependent kinase ...CKM complex / G0 to G1 transition / negative regulation of triglyceride metabolic process / mediator complex / Generic Transcription Pathway / [RNA-polymerase]-subunit kinase / cyclin-dependent protein serine/threonine kinase regulator activity / negative regulation of Notch signaling pathway / RSV-host interactions / cyclin-dependent kinase / cyclin-dependent protein serine/threonine kinase activity / cyclin-dependent protein kinase holoenzyme complex / ubiquitin ligase complex / RNA polymerase II CTD heptapeptide repeat kinase activity / SMAD2/SMAD3:SMAD4 heterotrimer regulates transcription / PPARA activates gene expression / NOTCH1 Intracellular Domain Regulates Transcription / Transcriptional regulation of white adipocyte differentiation / Constitutive Signaling by NOTCH1 PEST Domain Mutants / Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants / ubiquitin protein ligase activity / protein kinase activity / protein ubiquitination / protein serine kinase activity / protein serine/threonine kinase activity / nucleolus / positive regulation of transcription by RNA polymerase II / protein-containing complex / nucleoplasm / ATP binding / identical protein binding / nucleus
Similarity search - Function
Cyclin, C-terminal domain 2 / Cyclin C-terminal domain / Cyclin/Cyclin-like subunit Ssn8 / Cyclin-like / Cyclin A; domain 1 / Cyclin, N-terminal / Cyclin, N-terminal domain / Cyclin-like / domain present in cyclins, TFIIB and Retinoblastoma / Cyclin-like superfamily ...Cyclin, C-terminal domain 2 / Cyclin C-terminal domain / Cyclin/Cyclin-like subunit Ssn8 / Cyclin-like / Cyclin A; domain 1 / Cyclin, N-terminal / Cyclin, N-terminal domain / Cyclin-like / domain present in cyclins, TFIIB and Retinoblastoma / Cyclin-like superfamily / : / 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-JH8 / Cyclin-C / Cyclin-dependent kinase 8
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.7 Å
AuthorsBoettcher, J.
CitationJournal: Mol.Cancer Ther. / Year: 2020
Title: Selective and Potent CDK8/19 Inhibitors Enhance NK-Cell Activity and Promote Tumor Surveillance.
Authors: Hofmann, M.H. / Mani, R. / Engelhardt, H. / Impagnatiello, M.A. / Carotta, S. / Kerenyi, M. / Lorenzo-Herrero, S. / Bottcher, J. / Scharn, D. / Arnhof, H. / Zoephel, A. / Schnitzer, R. / ...Authors: Hofmann, M.H. / Mani, R. / Engelhardt, H. / Impagnatiello, M.A. / Carotta, S. / Kerenyi, M. / Lorenzo-Herrero, S. / Bottcher, J. / Scharn, D. / Arnhof, H. / Zoephel, A. / Schnitzer, R. / Gerstberger, T. / Sanderson, M.P. / Rajgolikar, G. / Goswami, S. / Vasu, S. / Ettmayer, P. / Gonzalez, S. / Pearson, M. / McConnell, D.B. / Kraut, N. / Muthusamy, N. / Moll, J.
History
DepositionFeb 25, 2019Deposition site: PDBE / Processing site: PDBE
Revision 1.0Mar 18, 2020Provider: repository / Type: Initial release
Revision 1.1Apr 22, 2020Group: Database references / Category: citation / citation_author
Item: _citation.country / _citation.journal_abbrev ..._citation.country / _citation.journal_abbrev / _citation.journal_id_CSD / _citation.journal_id_ISSN / _citation.journal_volume / _citation.page_first / _citation.page_last / _citation.pdbx_database_id_DOI / _citation.pdbx_database_id_PubMed / _citation.title / _citation.year
Revision 1.2Jan 24, 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 / refine
Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession / _refine.pdbx_diffrn_id

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Cyclin-dependent kinase 8
B: Cyclin-C
hetero molecules


Theoretical massNumber of molelcules
Total (without water)80,6713
Polymers80,3142
Non-polymers3561
Water3,621201
1


  • Idetical with deposited unit
  • defined by author&software
  • Evidence: gel filtration
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area3090 Å2
ΔGint-23 kcal/mol
Surface area27900 Å2
MethodPISA
Unit cell
Length a, b, c (Å)69.539, 73.922, 168.310
Angle α, β, γ (deg.)90.00, 90.00, 90.00
Int Tables number19
Space group name H-MP212121

-
Components

#1: Protein Cyclin-dependent kinase 8 / Cell division protein kinase 8 / Mediator complex subunit CDK8 / Mediator of RNA polymerase II ...Cell division protein kinase 8 / Mediator complex subunit CDK8 / Mediator of RNA polymerase II transcription subunit CDK8 / Protein kinase K35


Mass: 46890.664 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: CDK8 / Production host: Trichoplusia (butterflies/moths)
References: UniProt: P49336, cyclin-dependent kinase, [RNA-polymerase]-subunit kinase
#2: Protein Cyclin-C / SRB11 homolog / hSRB11


Mass: 33423.824 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: CCNC / Production host: Trichoplusia lectula (butterflies/moths) / References: UniProt: P24863
#3: Chemical ChemComp-JH8 / 2-[4-(4-isoquinolin-4-ylphenyl)pyrazol-1-yl]-~{N},~{N}-dimethyl-ethanamide


Mass: 356.420 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C22H20N4O
#4: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 201 / 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: 2.69 Å3/Da / Density % sol: 54.33 %
Crystal growTemperature: 278 K / Method: vapor diffusion, sitting drop
Details: 32-38% Morpheus Precipitant Mix 4 10 mmol/L Morpheus Buffer System 1 100 mM Morpheus Amino Acids Mix 2% DMSO
PH range: 6-7

-
Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: SLS / Beamline: X06SA / Wavelength: 1 Å
DetectorType: DECTRIS EIGER X 16M / Detector: PIXEL / Date: Aug 4, 2016
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1 Å / Relative weight: 1
ReflectionResolution: 2.702→84.2 Å / Num. obs: 24333 / % possible obs: 99.3 % / Redundancy: 10 % / Biso Wilson estimate: 69.6 Å2 / Net I/σ(I): 12.5
Reflection shellResolution: 2.702→2.749 Å

-
Processing

Software
NameVersionClassification
BUSTER2.11.7refinement
XDSdata reduction
STARANISOdata scaling
MOLREPphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 3RGF

3rgf


Resolution: 2.7→37.6 Å / Cor.coef. Fo:Fc: 0.922 / Cor.coef. Fo:Fc free: 0.899 / SU R Cruickshank DPI: 0.64 / Cross valid method: THROUGHOUT / σ(F): 0 / SU R Blow DPI: 0.73 / SU Rfree Blow DPI: 0.288 / SU Rfree Cruickshank DPI: 0.287
RfactorNum. reflection% reflectionSelection details
Rfree0.231 1111 4.58 %RANDOM
Rwork0.201 ---
obs0.202 24270 99 %-
Displacement parametersBiso mean: 56.98 Å2
Baniso -1Baniso -2Baniso -3
1-12.0763 Å20 Å20 Å2
2---22.3502 Å20 Å2
3---10.2739 Å2
Refine analyzeLuzzati coordinate error obs: 0.36 Å
Refinement stepCycle: LAST / Resolution: 2.7→37.6 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms4916 0 27 201 5144
Refine LS restraints
Refine-IDTypeDev idealNumberRestraint functionWeight
X-RAY DIFFRACTIONt_bond_d0.0085075HARMONIC2
X-RAY DIFFRACTIONt_angle_deg0.946854HARMONIC2
X-RAY DIFFRACTIONt_dihedral_angle_d1790SINUSOIDAL2
X-RAY DIFFRACTIONt_incorr_chiral_ct
X-RAY DIFFRACTIONt_pseud_angle
X-RAY DIFFRACTIONt_trig_c_planes
X-RAY DIFFRACTIONt_gen_planes829HARMONIC5
X-RAY DIFFRACTIONt_it5075HARMONIC20
X-RAY DIFFRACTIONt_nbd
X-RAY DIFFRACTIONt_omega_torsion2.35
X-RAY DIFFRACTIONt_other_torsion17.15
X-RAY DIFFRACTIONt_improper_torsion
X-RAY DIFFRACTIONt_chiral_improper_torsion629SEMIHARMONIC5
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_contact5915SEMIHARMONIC4
LS refinement shellResolution: 2.7→2.72 Å / Total num. of bins used: 50
RfactorNum. reflection% reflection
Rfree0.248 -5.76 %
Rwork0.2568 458 -
all0.2563 486 -
obs--98.02 %
Refinement TLS params.

Method: refined / Refine-ID: X-RAY DIFFRACTION

IDL11 (°2)L12 (°2)L13 (°2)L22 (°2)L23 (°2)L33 (°2)S11 (Å °)S12 (Å °)S13 (Å °)S21 (Å °)S22 (Å °)S23 (Å °)S31 (Å °)S32 (Å °)S33 (Å °)T11 (Å2)T12 (Å2)T13 (Å2)T22 (Å2)T23 (Å2)T33 (Å2)Origin x (Å)Origin y (Å)Origin z (Å)
11.9020.2856-0.13160.8526-0.07110.9512-0.09860.1476-0.0202-0.08760.1042-0.0227-0.04360.026-0.0056-0.12230.02240.0091-0.00590.0168-0.11472.8417-10.355815.0399
21.76530.59260.25951.6221-0.11593.03420.08060.03010.08390.07780.03530.0246-0.08160.0077-0.1158-0.20940.0780.0309-0.09410.0859-0.0526-16.2969-22.942644.5129
Refinement TLS group
IDRefine-IDRefine TLS-IDSelection details
1X-RAY DIFFRACTION1{ A|* }
2X-RAY DIFFRACTION2{ B|* }

+
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