[English] 日本語
Yorodumi
- PDB-7nxj: Crystal structure of human Cdk13/Cyclin K in complex with the inh... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 7nxj
TitleCrystal structure of human Cdk13/Cyclin K in complex with the inhibitor THZ531
Components
  • Cyclin-K
  • Cyclin-dependent kinase 13
KeywordsTRANSCRIPTION / CDK13 / Cyclin K / CCNK / THZ531 / kinase
Function / homology
Function and homology information


cyclin K-CDK12 complex / cyclin K-CDK13 complex / nuclear cyclin-dependent protein kinase holoenzyme complex / cyclin/CDK positive transcription elongation factor complex / negative regulation by host of viral genome replication / alternative mRNA splicing, via spliceosome / negative regulation of stem cell differentiation / cyclin-dependent protein serine/threonine kinase activator activity / positive regulation of DNA-templated transcription, elongation / [RNA-polymerase]-subunit kinase ...cyclin K-CDK12 complex / cyclin K-CDK13 complex / nuclear cyclin-dependent protein kinase holoenzyme complex / cyclin/CDK positive transcription elongation factor complex / negative regulation by host of viral genome replication / alternative mRNA splicing, via spliceosome / negative regulation of stem cell differentiation / cyclin-dependent protein serine/threonine kinase activator activity / positive regulation of DNA-templated transcription, elongation / [RNA-polymerase]-subunit kinase / regulation of cyclin-dependent protein serine/threonine kinase activity / hemopoiesis / RNA polymerase II transcribes snRNA genes / HIV elongation arrest and recovery / Pausing and recovery of HIV elongation / regulation of signal transduction / cyclin-dependent kinase / Formation of HIV elongation complex in the absence of HIV Tat / cyclin-dependent protein serine/threonine kinase activity / RNA Polymerase II Transcription Elongation / Formation of RNA Pol II elongation complex / RNA Polymerase II Pre-transcription Events / cyclin binding / RNA polymerase II CTD heptapeptide repeat kinase activity / TP53 Regulates Transcription of DNA Repair Genes / positive regulation of transcription elongation by RNA polymerase II / SMAD2/SMAD3:SMAD4 heterotrimer regulates transcription / ficolin-1-rich granule lumen / transcription by RNA polymerase II / protein kinase activity / nuclear speck / cell cycle / cell division / protein phosphorylation / protein serine kinase activity / DNA damage response / Neutrophil degranulation / regulation of transcription by RNA polymerase II / protein kinase binding / Golgi apparatus / positive regulation of transcription by RNA polymerase II / extracellular space / RNA binding / extracellular region / nucleoplasm / ATP binding / nucleus / cytosol
Similarity search - Function
Cyclin-T2-like, C-terminal domain / Haspin like kinase domain / Cyclin, C-terminal domain / Cyclin_C / Cyclin/Cyclin-like subunit Ssn8 / Cyclin, N-terminal / Cyclin, N-terminal domain / Cyclin-like / domain present in cyclins, TFIIB and Retinoblastoma / Cyclin-like superfamily ...Cyclin-T2-like, C-terminal domain / Haspin like kinase domain / Cyclin, C-terminal domain / Cyclin_C / Cyclin/Cyclin-like subunit Ssn8 / Cyclin, N-terminal / Cyclin, N-terminal domain / Cyclin-like / domain present in cyclins, TFIIB and Retinoblastoma / Cyclin-like superfamily / 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-5I1 / Cyclin-K / Cyclin-dependent kinase 13
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.36 Å
AuthorsAnand, K. / Greifenberg, A.K. / Kaltheuner, I.H. / Geyer, M.
Funding support Germany, 2items
OrganizationGrant numberCountry
German Research Foundation (DFG)GE 976/9-2 Germany
German Research Foundation (DFG)EXC2151-390873048 Germany
CitationJournal: Eur.J.Med.Chem. / Year: 2021
Title: Structure-activity relationship study of THZ531 derivatives enables the discovery of BSJ-01-175 as a dual CDK12/13 covalent inhibitor with efficacy in Ewing sarcoma.
Authors: Jiang, B. / Jiang, J. / Kaltheuner, I.H. / Iniguez, A.B. / Anand, K. / Ferguson, F.M. / Ficarro, S.B. / Seong, B.K.A. / Greifenberg, A.K. / Dust, S. / Kwiatkowski, N.P. / Marto, J.A. / ...Authors: Jiang, B. / Jiang, J. / Kaltheuner, I.H. / Iniguez, A.B. / Anand, K. / Ferguson, F.M. / Ficarro, S.B. / Seong, B.K.A. / Greifenberg, A.K. / Dust, S. / Kwiatkowski, N.P. / Marto, J.A. / Stegmaier, K. / Zhang, T. / Geyer, M. / Gray, N.S.
History
DepositionMar 18, 2021Deposition site: PDBE / Processing site: PDBE
Revision 1.0May 12, 2021Provider: repository / Type: Initial release
Revision 1.1Jan 31, 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: Cyclin-dependent kinase 13
B: Cyclin-K
C: Cyclin-dependent kinase 13
D: Cyclin-K
hetero molecules


Theoretical massNumber of molelcules
Total (without water)145,0226
Polymers143,9024
Non-polymers1,1202
Water1,49583
1
A: Cyclin-dependent kinase 13
B: Cyclin-K
hetero molecules


Theoretical massNumber of molelcules
Total (without water)72,5113
Polymers71,9512
Non-polymers5601
Water362
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area2080 Å2
ΔGint-6 kcal/mol
Surface area25920 Å2
MethodPISA
2
C: Cyclin-dependent kinase 13
D: Cyclin-K
hetero molecules


Theoretical massNumber of molelcules
Total (without water)72,5113
Polymers71,9512
Non-polymers5601
Water362
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area2310 Å2
ΔGint-6 kcal/mol
Surface area25900 Å2
MethodPISA
Unit cell
Length a, b, c (Å)49.880, 149.450, 92.010
Angle α, β, γ (deg.)90.00, 94.61, 90.00
Int Tables number4
Space group name H-MP1211

-
Components

#1: Protein Cyclin-dependent kinase 13 / / CDC2-related protein kinase 5 / Cell division cycle 2-like protein kinase 5 / Cell division protein ...CDC2-related protein kinase 5 / Cell division cycle 2-like protein kinase 5 / Cell division protein kinase 13 / hCDK13 / Cholinesterase-related cell division controller


Mass: 40521.863 Da / Num. of mol.: 2 / Fragment: UNP residues 694-1039
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: CDK13, CDC2L, CDC2L5, CHED, KIAA1791 / Production host: Spodoptera frugiperda (fall armyworm)
References: UniProt: Q14004, cyclin-dependent kinase, [RNA-polymerase]-subunit kinase
#2: Protein Cyclin-K


Mass: 31429.172 Da / Num. of mol.: 2
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: CCNK, CPR4 / Production host: Spodoptera frugiperda (fall armyworm) / References: UniProt: O75909
#3: Chemical ChemComp-5I1 / N-[4-[(3R)-3-[[5-chloranyl-4-(1H-indol-3-yl)pyrimidin-2-yl]amino]piperidin-1-yl]carbonylphenyl]-4-(dimethylamino)butanamide


Mass: 560.090 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C30H34ClN7O2 / Feature type: SUBJECT OF INVESTIGATION
#4: Water ChemComp-HOH / water / Water


Mass: 18.015 Da / Num. of mol.: 83 / 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: 2.36 Å3/Da / Density % sol: 47.83 %
Crystal growTemperature: 293 K / Method: vapor diffusion, hanging drop / pH: 6.8 / Details: 0.1 M MES (pH 6.8), 24% PEG 3350, 0.2 M MgCl2

-
Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: ESRF / Beamline: ID23-1 / Wavelength: 0.972422 Å
DetectorType: DECTRIS PILATUS 6M / Detector: PIXEL / Date: Feb 24, 2016
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.972422 Å / Relative weight: 1
ReflectionResolution: 2.36→45.86 Å / Num. obs: 54103 / % possible obs: 98.2 % / Redundancy: 3.4 % / Rrim(I) all: 0.06 / Net I/σ(I): 13.4
Reflection shellResolution: 2.36→2.44 Å / Num. unique obs: 5344 / Rrim(I) all: 0.77 / % possible all: 97.3

-
Processing

Software
NameVersionClassification
PHENIX(1.18.2_3874: ???)refinement
XDSdata reduction
XDSdata scaling
PHASERphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 5EFQ

5efq


Resolution: 2.36→45.86 Å / SU ML: 0.36 / Cross valid method: FREE R-VALUE / σ(F): 1.38 / Phase error: 29.78 / Stereochemistry target values: ML
RfactorNum. reflection% reflection
Rfree0.2518 1351 2.5 %
Rwork0.2121 --
obs0.2131 54078 98.15 %
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT BULK SOLVENT MODEL
Refinement stepCycle: LAST / Resolution: 2.36→45.86 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms9284 0 0 83 9367
Refine LS restraints
Refine-IDTypeDev idealNumber
X-RAY DIFFRACTIONf_bond_d0.0029504
X-RAY DIFFRACTIONf_angle_d0.60812885
X-RAY DIFFRACTIONf_dihedral_angle_d18.4043486
X-RAY DIFFRACTIONf_chiral_restr0.0411384
X-RAY DIFFRACTIONf_plane_restr0.0041638
LS refinement shell
Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkRefine-ID% reflection obs (%)
2.36-2.440.34551340.31885210X-RAY DIFFRACTION98
2.44-2.540.37911350.29685295X-RAY DIFFRACTION98
2.54-2.660.31351350.28565259X-RAY DIFFRACTION98
2.66-2.80.33131320.27995183X-RAY DIFFRACTION97
2.8-2.970.33611360.26575335X-RAY DIFFRACTION99
2.97-3.20.33491360.25695286X-RAY DIFFRACTION99
3.2-3.520.24051350.23165283X-RAY DIFFRACTION98
3.53-4.030.26891350.215232X-RAY DIFFRACTION97
4.04-5.080.20721350.17065295X-RAY DIFFRACTION98
5.08-45.860.1971380.17545349X-RAY DIFFRACTION98
Refinement TLS params.Method: refined / Origin x: 28.789 Å / Origin y: 26.698 Å / Origin z: 29.554 Å
111213212223313233
T0.3674 Å2-0.0588 Å20.0492 Å2-0.431 Å2-0.0322 Å2--0.4299 Å2
L0.4146 °2-0.1636 °20.3958 °2-0.2076 °2-0.1501 °2--0.9953 °2
S-0.0094 Å °-0.0877 Å °0.0518 Å °0.0672 Å °0.0156 Å °-0.0414 Å °-0.1346 Å °-0.0785 Å °-0.0074 Å °
Refinement TLS group
IDRefine-IDRefine TLS-IDSelection detailsAuth asym-IDAuth seq-ID
1X-RAY DIFFRACTION1( CHAIN A AND ( RESID 695:1023 OR RESID 2000:2000 OR RESID 2101:2116 ) ) OR ( CHAIN C AND ( RESID 695:1017 OR RESID 2000:2000 OR RESID 2101:2125 ) ) OR ( CHAIN B AND ( RESID 21:264 OR RESID 301:317 ) ) OR ( CHAIN D AND ( RESID 301:325 OR RESID 21:267 ) )A695 - 1023
2X-RAY DIFFRACTION1( CHAIN A AND ( RESID 695:1023 OR RESID 2000:2000 OR RESID 2101:2116 ) ) OR ( CHAIN C AND ( RESID 695:1017 OR RESID 2000:2000 OR RESID 2101:2125 ) ) OR ( CHAIN B AND ( RESID 21:264 OR RESID 301:317 ) ) OR ( CHAIN D AND ( RESID 301:325 OR RESID 21:267 ) )A2000
3X-RAY DIFFRACTION1( CHAIN A AND ( RESID 695:1023 OR RESID 2000:2000 OR RESID 2101:2116 ) ) OR ( CHAIN C AND ( RESID 695:1017 OR RESID 2000:2000 OR RESID 2101:2125 ) ) OR ( CHAIN B AND ( RESID 21:264 OR RESID 301:317 ) ) OR ( CHAIN D AND ( RESID 301:325 OR RESID 21:267 ) )A2101 - 2116
4X-RAY DIFFRACTION1( CHAIN A AND ( RESID 695:1023 OR RESID 2000:2000 OR RESID 2101:2116 ) ) OR ( CHAIN C AND ( RESID 695:1017 OR RESID 2000:2000 OR RESID 2101:2125 ) ) OR ( CHAIN B AND ( RESID 21:264 OR RESID 301:317 ) ) OR ( CHAIN D AND ( RESID 301:325 OR RESID 21:267 ) )C695 - 1017
5X-RAY DIFFRACTION1( CHAIN A AND ( RESID 695:1023 OR RESID 2000:2000 OR RESID 2101:2116 ) ) OR ( CHAIN C AND ( RESID 695:1017 OR RESID 2000:2000 OR RESID 2101:2125 ) ) OR ( CHAIN B AND ( RESID 21:264 OR RESID 301:317 ) ) OR ( CHAIN D AND ( RESID 301:325 OR RESID 21:267 ) )C2000
6X-RAY DIFFRACTION1( CHAIN A AND ( RESID 695:1023 OR RESID 2000:2000 OR RESID 2101:2116 ) ) OR ( CHAIN C AND ( RESID 695:1017 OR RESID 2000:2000 OR RESID 2101:2125 ) ) OR ( CHAIN B AND ( RESID 21:264 OR RESID 301:317 ) ) OR ( CHAIN D AND ( RESID 301:325 OR RESID 21:267 ) )C2101 - 2125
7X-RAY DIFFRACTION1( CHAIN A AND ( RESID 695:1023 OR RESID 2000:2000 OR RESID 2101:2116 ) ) OR ( CHAIN C AND ( RESID 695:1017 OR RESID 2000:2000 OR RESID 2101:2125 ) ) OR ( CHAIN B AND ( RESID 21:264 OR RESID 301:317 ) ) OR ( CHAIN D AND ( RESID 301:325 OR RESID 21:267 ) )B21 - 264
8X-RAY DIFFRACTION1( CHAIN A AND ( RESID 695:1023 OR RESID 2000:2000 OR RESID 2101:2116 ) ) OR ( CHAIN C AND ( RESID 695:1017 OR RESID 2000:2000 OR RESID 2101:2125 ) ) OR ( CHAIN B AND ( RESID 21:264 OR RESID 301:317 ) ) OR ( CHAIN D AND ( RESID 301:325 OR RESID 21:267 ) )B301 - 317
9X-RAY DIFFRACTION1( CHAIN A AND ( RESID 695:1023 OR RESID 2000:2000 OR RESID 2101:2116 ) ) OR ( CHAIN C AND ( RESID 695:1017 OR RESID 2000:2000 OR RESID 2101:2125 ) ) OR ( CHAIN B AND ( RESID 21:264 OR RESID 301:317 ) ) OR ( CHAIN D AND ( RESID 301:325 OR RESID 21:267 ) )D301 - 325
10X-RAY DIFFRACTION1( CHAIN A AND ( RESID 695:1023 OR RESID 2000:2000 OR RESID 2101:2116 ) ) OR ( CHAIN C AND ( RESID 695:1017 OR RESID 2000:2000 OR RESID 2101:2125 ) ) OR ( CHAIN B AND ( RESID 21:264 OR RESID 301:317 ) ) OR ( CHAIN D AND ( RESID 301:325 OR RESID 21:267 ) )D21 - 267

+
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