[English] 日本語
Yorodumi
- PDB-4bci: Structure of CDK9 in complex with cyclin T and a 2-amino-4-hetero... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 4bci
TitleStructure of CDK9 in complex with cyclin T and a 2-amino-4-heteroaryl- pyrimidine inhibitor
Components
  • CYCLIN-DEPENDENT KINASE 9
  • CYCLIN-T1
KeywordsTRANSFERASE/CELL CYCLE / TRANSFERASE-CELL CYCLE COMPLEX / CDK-CYCLIN COMPLEX / TRANSCRIPTION-PROTEIN BINDING / STRUCTURE-BASED DRUG DESIGN
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 mRNA 3'-end processing / positive regulation of protein localization to chromatin / regulation of muscle cell differentiation / transcription elongation factor activity / regulation of cyclin-dependent protein serine/threonine 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 mRNA 3'-end processing / positive regulation of protein localization to chromatin / regulation of muscle cell differentiation / transcription elongation factor activity / regulation of cyclin-dependent protein serine/threonine kinase activity / host-mediated activation of viral transcription / cyclin-dependent protein serine/threonine kinase activator activity / RNA polymerase binding / positive regulation of DNA-templated transcription, elongation / [RNA-polymerase]-subunit kinase / negative regulation of protein localization to chromatin / 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 / cyclin-dependent protein serine/threonine kinase activity / Tat-mediated elongation of the HIV-1 transcript / Formation of HIV-1 elongation complex containing HIV-1 Tat / regulation of DNA repair / Formation of HIV elongation complex in the absence of HIV Tat / 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 / TP53 Regulates Transcription of DNA Repair Genes / transcription initiation at RNA polymerase II promoter / transcription elongation by RNA polymerase II / positive regulation of transcription elongation by RNA polymerase II / SMAD2/SMAD3:SMAD4 heterotrimer regulates transcription / molecular condensate scaffold activity / PML body / transcription coactivator binding / cytoplasmic ribonucleoprotein granule / kinase activity / DNA-binding transcription factor binding / Estrogen-dependent gene expression / transcription by RNA polymerase II / cell population proliferation / protein phosphorylation / protein kinase activity / transcription cis-regulatory region binding / regulation of cell cycle / 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-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-T2-like, 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 / : / Phosphorylase Kinase; domain 1 / Phosphorylase Kinase; domain 1 / Transferase(Phosphotransferase) domain 1 / Transferase(Phosphotransferase); 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-T3E / Cyclin-T1 / Cyclin-dependent kinase 9
Similarity search - Component
Biological speciesHOMO SAPIENS (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / OTHER / Resolution: 3.1 Å
AuthorsHole, A.J. / Baumli, S. / Wang, S. / Endicott, J.A. / Noble, M.E.M.
CitationJournal: J.Med.Chem. / Year: 2013
Title: Comparative Structural and Functional Studies of 4-(Thiazol- 5-Yl)-2-(Phenylamino)Pyrimidine-5-Carbonitrile Cdk9 Inhibitors Suggest the Basis for Isotype Selectivity.
Authors: Hole, A.J. / Baumli, S. / Shao, H. / Shi, S. / Pepper, C. / Fischer, P.M. / Wang, S. / Endicott, J.A. / Noble, M.E.M.
History
DepositionOct 2, 2012Deposition site: PDBE / Processing site: PDBE
Revision 1.0Jan 9, 2013Provider: repository / Type: Initial release
Revision 1.1Feb 27, 2013Group: Database references
Revision 1.2May 15, 2019Group: Data collection / Derived calculations ...Data collection / Derived calculations / Experimental preparation / Other
Category: exptl_crystal_grow / pdbx_database_proc ...exptl_crystal_grow / pdbx_database_proc / pdbx_database_status / struct_conn
Item: _exptl_crystal_grow.temp / _pdbx_database_status.recvd_author_approval / _struct_conn.pdbx_leaving_atom_flag
Revision 1.3Nov 13, 2024Group: Data collection / Database references ...Data collection / Database references / Derived calculations / Other / Structure summary
Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / database_2 / pdbx_database_status / pdbx_entry_details / pdbx_modification_feature / struct_conn / struct_site
Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession ..._database_2.pdbx_DOI / _database_2.pdbx_database_accession / _pdbx_database_status.status_code_sf / _struct_conn.ptnr1_auth_comp_id / _struct_conn.ptnr1_auth_seq_id / _struct_conn.ptnr1_label_atom_id / _struct_conn.ptnr1_label_comp_id / _struct_conn.ptnr1_label_seq_id / _struct_conn.ptnr2_auth_comp_id / _struct_conn.ptnr2_auth_seq_id / _struct_conn.ptnr2_label_atom_id / _struct_conn.ptnr2_label_comp_id / _struct_conn.ptnr2_label_seq_id / _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 9
B: CYCLIN-T1
hetero molecules


Theoretical massNumber of molelcules
Total (without water)68,5753
Polymers68,1742
Non-polymers4011
Water1448
1


  • Idetical with deposited unit
  • defined by software
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area1730 Å2
ΔGint-12 kcal/mol
Surface area28420 Å2
MethodPISA
Unit cell
Length a, b, c (Å)174.110, 174.110, 99.261
Angle α, β, γ (deg.)90.00, 90.00, 120.00
Int Tables number146
Space group name H-MH3

-
Components

#1: Protein CYCLIN-DEPENDENT KINASE 9 / C-2K / CELL DIVISION CYCLE 2-LIKE PROTEIN KINASE 4 / CELL DIVISION PROTEIN KINASE 9 / ...C-2K / CELL DIVISION CYCLE 2-LIKE PROTEIN KINASE 4 / CELL DIVISION PROTEIN KINASE 9 / SERINE/THREONINE-PROTEIN KINASE PITALRE / TAT-ASSOCIATED KINASE COMPLEX CATALYTIC SUBUNIT


Mass: 38054.082 Da / Num. of mol.: 1 / Fragment: RESIDUES 2-330
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) HOMO SAPIENS (human) / Plasmid: PVL1392 / Production host: SPODOPTERA FRUGIPERDA (fall armyworm) / Strain (production host): SF9
References: UniProt: P50750, cyclin-dependent kinase, [RNA-polymerase]-subunit kinase
#2: Protein CYCLIN-T1 / CYCT1 / CYCLIN-T


Mass: 30119.426 Da / Num. of mol.: 1 / Fragment: RESIDUES 2-259 / Mutation: YES
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) HOMO SAPIENS (human) / Plasmid: PVL1392 / Production host: SPODOPTERA FRUGIPERDA (fall armyworm) / Strain (production host): SF9 / References: UniProt: O60563
#3: Chemical ChemComp-T3E / 3-[[5-cyano-4-[4-methyl-2-(methylamino)-1,3-thiazol-5-yl]pyrimidin-2-yl]amino]benzenesulfonamide


Mass: 401.466 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C16H15N7O2S2
#4: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 8 / Source method: isolated from a natural source / Formula: H2O
Has protein modificationY

-
Experimental details

-
Experiment

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

-
Sample preparation

CrystalDensity Matthews: 2.3 Å3/Da / Density % sol: 47 % / Description: NONE
Crystal growTemperature: 277 K / pH: 6.2
Details: CRYSTALS WERE GROWN AT 4C USING 10-16% PEG 1000, 100MM NAK-PHOSPHATE PH 6.2, 500MM NACL, 4MM TCEP AS THE PRECIPITANT SOLUTION. THEY WERE SUBSEQUENTLY SOAKED IN THE PRESENCE OF COMPOUND.

-
Data collection

DiffractionMean temperature: 100 K
Diffraction sourceSource: SYNCHROTRON / Site: Diamond / Beamline: I02 / Wavelength: 0.979
DetectorType: ADSC CCD / Detector: CCD
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.979 Å / Relative weight: 1
ReflectionResolution: 2.97→60.04 Å / Num. obs: 20202 / % possible obs: 99.3 % / Redundancy: 3.63 % / Rmerge(I) obs: 0.06 / Net I/σ(I): 8.61
Reflection shellResolution: 3.1→3.27 Å / Redundancy: 3.68 % / Rmerge(I) obs: 0.59 / Mean I/σ(I) obs: 1.29 / % possible all: 99.5

-
Processing

Software
NameVersionClassification
REFMAC5.7.0029refinement
PHENIXphasing
RefinementMethod to determine structure: OTHER / Resolution: 3.1→37.428 Å / Cor.coef. Fo:Fc: 0.964 / Cor.coef. Fo:Fc free: 0.943 / SU B: 38.216 / SU ML: 0.295 / Cross valid method: THROUGHOUT / ESU R: 1.356 / ESU R Free: 0.343 / Stereochemistry target values: MAXIMUM LIKELIHOOD / Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS.
RfactorNum. reflection% reflection
Rfree0.2213 1024 5.19 %
Rwork0.1777 --
obs0.18 20201 99.292 %
Solvent computationIon probe radii: 0.8 Å / VDW probe radii: 1.2 Å / Solvent model: MASK BULK SOLVENT
Displacement parametersBiso mean: 110.632 Å2
Baniso -1Baniso -2Baniso -3
1--4.036 Å2-4.036 Å20 Å2
2---4.036 Å20 Å2
3---13.093 Å2
Refinement stepCycle: LAST / Resolution: 3.1→37.428 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms4562 0 27 8 4597
Refine LS restraints
Refine-IDTypeDev idealDev ideal targetNumber
X-RAY DIFFRACTIONr_bond_refined_d0.0090.0194695
X-RAY DIFFRACTIONr_bond_other_d0.0010.024542
X-RAY DIFFRACTIONr_angle_refined_deg1.1251.9696370
X-RAY DIFFRACTIONr_angle_other_deg0.625310432
X-RAY DIFFRACTIONr_dihedral_angle_1_deg4.9645557
X-RAY DIFFRACTIONr_dihedral_angle_2_deg33.55123.945218
X-RAY DIFFRACTIONr_dihedral_angle_3_deg15.48615835
X-RAY DIFFRACTIONr_dihedral_angle_4_deg16.851531
X-RAY DIFFRACTIONr_chiral_restr0.0730.2710
X-RAY DIFFRACTIONr_gen_planes_refined0.0070.0215210
X-RAY DIFFRACTIONr_gen_planes_other0.0010.021088
X-RAY DIFFRACTIONr_nbd_refined0.3550.240
X-RAY DIFFRACTIONr_nbd_other0.1930.230
X-RAY DIFFRACTIONr_nbtor_refined0.2070.270
X-RAY DIFFRACTIONr_nbtor_other
X-RAY DIFFRACTIONr_xyhbond_nbd_refined0.2220.24
X-RAY DIFFRACTIONr_xyhbond_nbd_other
X-RAY DIFFRACTIONr_metal_ion_refined
X-RAY DIFFRACTIONr_metal_ion_other
X-RAY DIFFRACTIONr_symmetry_vdw_refined
X-RAY DIFFRACTIONr_symmetry_vdw_other
X-RAY DIFFRACTIONr_symmetry_hbond_refined
X-RAY DIFFRACTIONr_symmetry_hbond_other
X-RAY DIFFRACTIONr_symmetry_metal_ion_refined
X-RAY DIFFRACTIONr_symmetry_metal_ion_other
X-RAY DIFFRACTIONr_mcbond_it6.6446.8024695
X-RAY DIFFRACTIONr_mcbond_other1.6886.9414542
X-RAY DIFFRACTIONr_mcangle_it13.67814.215206
X-RAY DIFFRACTIONr_mcangle_other
X-RAY DIFFRACTIONr_scbond_it7.94331.1259
X-RAY DIFFRACTIONr_scbond_other
X-RAY DIFFRACTIONr_scangle_it12.04565.71915037
X-RAY DIFFRACTIONr_scangle_other
X-RAY DIFFRACTIONr_long_range_B_refined
X-RAY DIFFRACTIONr_long_range_B_other
X-RAY DIFFRACTIONr_rigid_bond_restr
X-RAY DIFFRACTIONr_sphericity_free
X-RAY DIFFRACTIONr_sphericity_bonded
LS refinement shellResolution: 3.1→3.18 Å / Total num. of bins used: 20
RfactorNum. reflection% reflection
Rfree0.429 82 -
Rwork0.326 1393 -
obs--99.595 %
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)
12.1473-0.03950.29992.5227-0.44572.78090.274-0.1927-0.72540.415-0.209-0.13770.66030.1117-0.0650.5303-0.0647-0.11390.3980.07110.254348.3031-17.9323-1.7599
23.6174-1.687-0.8552.4917-0.03251.7101-0.01130.04160.36580.08440.0927-0.214-0.1638-0.0031-0.08140.3178-0.0686-0.05840.4115-0.0120.050421.68273.5791-19.9134
Refinement TLS group
IDRefine-IDRefine TLS-IDAuth asym-IDAuth seq-ID
1X-RAY DIFFRACTION1A5 - 326
2X-RAY DIFFRACTION2B8 - 259

+
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