[English] 日本語
Yorodumi
- PDB-8k5r: CDK9/cyclin T1 in complex with KB-0742 -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 8k5r
TitleCDK9/cyclin T1 in complex with KB-0742
Components
  • Cyclin-T1
  • Cyclin-dependent kinase 9
KeywordsTRANSCRIPTION / KB-0742 / CDK9/cyclin T1 / CDK9 / cyclin T1
Function / homology
Function and homology information


P-TEFb complex / Interactions of Tat with host cellular proteins / nucleus localization / 7SK snRNA binding / cyclin/CDK positive transcription elongation factor complex / regulation of muscle cell differentiation / regulation of mRNA 3'-end processing / positive regulation of protein localization to chromatin / RNA polymerase II CTD heptapeptide repeat Y1 kinase activity / RNA polymerase II CTD heptapeptide repeat S2 kinase activity ...P-TEFb complex / Interactions of Tat with host cellular proteins / nucleus localization / 7SK snRNA binding / cyclin/CDK positive transcription elongation factor complex / regulation of muscle cell differentiation / regulation of mRNA 3'-end processing / positive regulation of protein localization to chromatin / RNA polymerase II CTD heptapeptide repeat Y1 kinase activity / RNA polymerase II CTD heptapeptide repeat S2 kinase activity / RNA polymerase II CTD heptapeptide repeat T4 kinase activity / RNA polymerase II CTD heptapeptide repeat S5 kinase activity / RNA polymerase II CTD heptapeptide repeat S7 kinase activity / transcription elongation factor activity / cyclin-dependent protein serine/threonine kinase activator activity / positive regulation by host of viral transcription / positive regulation of DNA-templated transcription, elongation / RNA polymerase binding / [RNA-polymerase]-subunit kinase / negative regulation of protein localization to chromatin / regulation of cyclin-dependent protein serine/threonine kinase activity / transcription elongation-coupled chromatin remodeling / cellular response to cytokine stimulus / replication fork processing / Pausing and recovery of Tat-mediated HIV elongation / Tat-mediated HIV elongation arrest and recovery / RNA polymerase II transcribes snRNA genes / HIV elongation arrest and recovery / Pausing and recovery of HIV elongation / cyclin-dependent kinase / Tat-mediated elongation of the HIV-1 transcript / cyclin-dependent protein serine/threonine kinase activity / Formation of HIV-1 elongation complex containing HIV-1 Tat / Formation of HIV elongation complex in the absence of HIV Tat / regulation of DNA repair / RNA Polymerase II Transcription Elongation / Formation of RNA Pol II elongation complex / RNA Polymerase II Pre-transcription Events / RNA polymerase II CTD heptapeptide repeat kinase activity / transcription elongation factor complex / positive regulation of transcription elongation by RNA polymerase II / TP53 Regulates Transcription of DNA Repair Genes / transcription initiation at RNA polymerase II promoter / transcription elongation by RNA polymerase II / SMAD2/SMAD3:SMAD4 heterotrimer regulates transcription / molecular condensate scaffold activity / transcription coactivator binding / PML body / cytoplasmic ribonucleoprotein granule / kinase activity / DNA-binding transcription factor binding / Estrogen-dependent gene expression / transcription by RNA polymerase II / cell population proliferation / protein kinase activity / transcription cis-regulatory region binding / regulation of cell cycle / protein phosphorylation / RNA polymerase II cis-regulatory region sequence-specific DNA binding / response to xenobiotic stimulus / cell division / protein serine kinase activity / DNA repair / protein serine/threonine kinase activity / chromatin binding / protein kinase binding / positive regulation of transcription by RNA polymerase II / DNA binding / nucleoplasm / ATP binding / nucleus / membrane / cytosol
Similarity search - Function
: / Cyclin-T2-like, C-terminal domain / 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 ...: / Cyclin-T2-like, C-terminal domain / 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-VQE / Cyclin-T1 / Cyclin-dependent kinase 9
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 3.751 Å
AuthorsZhou, M. / Li, H. / Gao, H. / Trotter, B.W. / Freeman, D.
Funding support1items
OrganizationGrant numberCountry
Not funded
CitationJournal: J.Med.Chem. / Year: 2023
Title: Discovery of KB-0742, a Potent, Selective, Orally Bioavailable Small Molecule Inhibitor of CDK9 for MYC-Dependent Cancers.
Authors: Freeman, D.B. / Hopkins, T.D. / Mikochik, P.J. / Vacca, J.P. / Gao, H. / Naylor-Olsen, A. / Rudra, S. / Li, H. / Pop, M.S. / Villagomez, R.A. / Lee, C. / Li, H. / Zhou, M. / Saffran, D.C. / ...Authors: Freeman, D.B. / Hopkins, T.D. / Mikochik, P.J. / Vacca, J.P. / Gao, H. / Naylor-Olsen, A. / Rudra, S. / Li, H. / Pop, M.S. / Villagomez, R.A. / Lee, C. / Li, H. / Zhou, M. / Saffran, D.C. / Rioux, N. / Hood, T.R. / Day, M.A.L. / McKeown, M.R. / Lin, C.Y. / Bischofberger, N. / Trotter, B.W.
History
DepositionJul 24, 2023Deposition site: PDBJ / Processing site: PDBJ
Revision 1.0Dec 6, 2023Provider: repository / Type: Initial release
Revision 1.1Dec 27, 2023Group: Database references / Category: citation / citation_author
Item: _citation.journal_volume / _citation.page_first ..._citation.journal_volume / _citation.page_first / _citation.page_last / _citation_author.identifier_ORCID
Revision 1.2Nov 13, 2024Group: Structure summary / Category: pdbx_entry_details / pdbx_modification_feature / Item: _pdbx_entry_details.has_protein_modification

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Cyclin-dependent kinase 9
B: Cyclin-T1
hetero molecules


Theoretical massNumber of molelcules
Total (without water)68,3833
Polymers68,0952
Non-polymers2871
Water00
1


  • Idetical with deposited unit
  • defined by author&software
  • Evidence: gel filtration
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area1850 Å2
ΔGint-12 kcal/mol
Surface area27900 Å2
MethodPISA
Unit cell
Length a, b, c (Å)171.502, 171.502, 96.122
Angle α, β, γ (deg.)90.000, 90.000, 120.000
Int Tables number146
Space group name H-MH3

-
Components

#1: Protein Cyclin-dependent kinase 9


Mass: 38057.047 Da / Num. of mol.: 1 / Mutation: S7D,V8N,K44R,Y138F,K280A,D307E,N311E
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: CDK9 / Production host: Spodoptera frugiperda (fall armyworm) / References: UniProt: P50750
#2: Protein Cyclin-T1


Mass: 30038.352 Da / Num. of mol.: 1 / Mutation: R26A,Q77R,E96G,K106R,F241L
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: CCNT1 / Production host: Spodoptera frugiperda (fall armyworm) / References: UniProt: O60563
#3: Chemical ChemComp-VQE / (1S,3S)-N3-(5-pentan-3-ylpyrazolo[1,5-a]pyrimidin-7-yl)cyclopentane-1,3-diamine


Mass: 287.403 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C16H25N5 / Feature type: SUBJECT OF INVESTIGATION
Has ligand of interestY
Has protein modificationY

-
Experimental details

-
Experiment

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

-
Sample preparation

CrystalDensity Matthews: 4 Å3/Da / Density % sol: 69.21 %
Crystal growTemperature: 277 K / Method: vapor diffusion, sitting drop / Details: 0.2M K3 citrate, 20% PEG3350

-
Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: SPring-8 / Beamline: BL41XU / Wavelength: 0.99999 Å
DetectorType: DECTRIS EIGER X 16M / Detector: PIXEL / Date: Jul 16, 2021
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.99999 Å / Relative weight: 1
ReflectionResolution: 3.75→85.751 Å / Num. obs: 10792 / % possible obs: 99.7 % / Redundancy: 4.7 % / Rmerge(I) obs: 0.062 / Net I/σ(I): 11.6
Reflection shellResolution: 3.75→4.19 Å / Rmerge(I) obs: 0.683 / Num. unique obs: 3092

-
Processing

Software
NameVersionClassification
REFMAC5.8.0352refinement
XDSdata reduction
Aimlessdata scaling
PHASERphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT / Resolution: 3.751→85.751 Å / Cor.coef. Fo:Fc: 0.937 / Cor.coef. Fo:Fc free: 0.948 / WRfactor Rfree: 0.246 / WRfactor Rwork: 0.2 / SU B: 42.14 / SU ML: 0.551 / Average fsc free: 0.9538 / Average fsc work: 0.9625 / Cross valid method: FREE R-VALUE / ESU R Free: 0.625
Details: Hydrogens have been added in their riding positions
RfactorNum. reflection% reflection
Rfree0.2455 537 4.977 %
Rwork0.2002 10252 -
all0.203 --
obs-10789 99.732 %
Solvent computationIon probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.2 Å / Solvent model: MASK BULK SOLVENT
Displacement parametersBiso mean: 200.665 Å2
Baniso -1Baniso -2Baniso -3
1--2.508 Å2-1.254 Å20 Å2
2---2.508 Å2-0 Å2
3---8.135 Å2
Refinement stepCycle: LAST / Resolution: 3.751→85.751 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms4537 0 21 0 4558
Refine LS restraints
Refine-IDTypeDev idealDev ideal targetNumber
X-RAY DIFFRACTIONr_bond_refined_d0.0030.0124661
X-RAY DIFFRACTIONr_bond_other_d0.0040.0164330
X-RAY DIFFRACTIONr_angle_refined_deg0.8561.6516321
X-RAY DIFFRACTIONr_angle_other_deg0.31.56510092
X-RAY DIFFRACTIONr_dihedral_angle_1_deg6.6125552
X-RAY DIFFRACTIONr_dihedral_angle_2_deg2.549532
X-RAY DIFFRACTIONr_dihedral_angle_3_deg13.4910831
X-RAY DIFFRACTIONr_dihedral_angle_6_deg11.49210218
X-RAY DIFFRACTIONr_chiral_restr0.0390.2711
X-RAY DIFFRACTIONr_gen_planes_refined0.0030.025181
X-RAY DIFFRACTIONr_gen_planes_other0.0010.02905
X-RAY DIFFRACTIONr_nbd_refined0.2340.2970
X-RAY DIFFRACTIONr_symmetry_nbd_other0.190.24150
X-RAY DIFFRACTIONr_nbtor_refined0.1760.22288
X-RAY DIFFRACTIONr_symmetry_nbtor_other0.0740.22432
X-RAY DIFFRACTIONr_xyhbond_nbd_refined0.1310.2120
X-RAY DIFFRACTIONr_symmetry_xyhbond_nbd_other0.0960.22
X-RAY DIFFRACTIONr_symmetry_nbd_refined0.2220.213
X-RAY DIFFRACTIONr_nbd_other0.2310.226
X-RAY DIFFRACTIONr_symmetry_xyhbond_nbd_refined0.0960.23
X-RAY DIFFRACTIONr_mcbond_it9.71920.5172226
X-RAY DIFFRACTIONr_mcbond_other9.71920.5172226
X-RAY DIFFRACTIONr_mcangle_it15.46530.7592772
X-RAY DIFFRACTIONr_mcangle_other15.46230.7592773
X-RAY DIFFRACTIONr_scbond_it8.46520.892435
X-RAY DIFFRACTIONr_scbond_other8.46320.8892436
X-RAY DIFFRACTIONr_scangle_it13.96331.1613549
X-RAY DIFFRACTIONr_scangle_other13.96231.163550
X-RAY DIFFRACTIONr_lrange_it19.833254.795253
X-RAY DIFFRACTIONr_lrange_other19.832254.7635254
LS refinement shell

Refine-ID: X-RAY DIFFRACTION / Total num. of bins used: 20

Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkRfactor allNum. reflection allFsc freeFsc work% reflection obs (%)WRfactor Rwork
3.751-3.8480.375340.3767940.3768280.9060.91000.376
3.848-3.9530.349580.3396970.347550.9290.9211000.339
3.953-4.0680.308290.2817330.2827620.9340.9481000.281
4.068-4.1930.298420.2377000.2417420.9490.9661000.237
4.193-4.330.256470.2396560.2417030.9640.9651000.239
4.33-4.4810.329260.2226670.2266930.9380.9681000.222
4.481-4.650.224290.1936430.1956720.9670.9761000.193
4.65-4.8390.231250.2015900.2026150.9680.9751000.201
4.839-5.0540.259320.2015950.2046270.9620.9741000.201
5.054-5.2990.257320.1915550.1955870.9610.981000.191
5.299-5.5850.299170.2115510.2135690.9470.97599.82430.211
5.585-5.9220.352210.2114940.2175160.9540.97699.80620.211
5.922-6.3290.266340.2154540.2184900.9710.97499.59180.215
6.329-6.8330.223200.2264460.2264670.9720.97399.78590.226
6.833-7.480.313110.1874210.1914350.9680.97899.31030.187
7.48-8.3550.204240.1543430.1573690.9760.98599.4580.154
8.355-9.6320.174170.1343290.1363500.9850.98998.85710.134
9.632-11.760.198130.1462730.1482910.9660.98898.28180.146
11.76-16.4770.217180.1521980.1582190.9760.98598.63010.152
16.477-85.7510.27180.3691120.3621270.9510.87894.48820.369

+
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