[English] 日本語
Yorodumi
- PDB-8h6t: Complex structure of CDK2/Cyclin E1 and a potent, selective small... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 8h6t
TitleComplex structure of CDK2/Cyclin E1 and a potent, selective small molecule inhibitor
Components
  • Cyclin-dependent kinase 2
  • G1/S-specific cyclin-E1
KeywordsCELL CYCLE / Inhibitor / Complex / Selective / Anti-tumor
Function / homology
Function and homology information


positive regulation of mesenchymal stem cell proliferation / homologous chromosome pairing at meiosis / RHOBTB3 ATPase cycle / cyclin-dependent protein serine/threonine kinase regulator activity / cyclin A1-CDK2 complex / cyclin E2-CDK2 complex / cyclin E1-CDK2 complex / cyclin A2-CDK2 complex / positive regulation of DNA-templated DNA replication initiation / G2 Phase ...positive regulation of mesenchymal stem cell proliferation / homologous chromosome pairing at meiosis / RHOBTB3 ATPase cycle / cyclin-dependent protein serine/threonine kinase regulator activity / cyclin A1-CDK2 complex / cyclin E2-CDK2 complex / cyclin E1-CDK2 complex / cyclin A2-CDK2 complex / positive regulation of DNA-templated DNA replication initiation / G2 Phase / Y chromosome / cyclin-dependent protein kinase activity / Phosphorylation of proteins involved in G1/S transition by active Cyclin E:Cdk2 complexes / positive regulation of heterochromatin formation / p53-Dependent G1 DNA Damage Response / X chromosome / G1/S-Specific Transcription / PTK6 Regulates Cell Cycle / regulation of anaphase-promoting complex-dependent catabolic process / Association of TriC/CCT with target proteins during biosynthesis / Defective binding of RB1 mutants to E2F1,(E2F2, E2F3) / centriole replication / Regulation of APC/C activators between G1/S and early anaphase / telomere maintenance in response to DNA damage / microtubule organizing center / centrosome duplication / G0 and Early G1 / Telomere Extension By Telomerase / DNA replication initiation / Activation of the pre-replicative complex / positive regulation of G1/S transition of mitotic cell cycle / cyclin-dependent kinase / cyclin-dependent protein serine/threonine kinase activity / TP53 Regulates Transcription of Genes Involved in G1 Cell Cycle Arrest / Cajal body / Regulation of MITF-M-dependent genes involved in cell cycle and proliferation / Activation of ATR in response to replication stress / Cyclin E associated events during G1/S transition / Cyclin A/B1/B2 associated events during G2/M transition / Cyclin A:Cdk2-associated events at S phase entry / cyclin-dependent protein kinase holoenzyme complex / condensed chromosome / regulation of G2/M transition of mitotic cell cycle / mitotic G1 DNA damage checkpoint signaling / cellular response to nitric oxide / telomere maintenance / post-translational protein modification / cyclin binding / regulation of mitotic cell cycle / positive regulation of DNA replication / meiotic cell cycle / male germ cell nucleus / G1/S transition of mitotic cell cycle / peptidyl-serine phosphorylation / DNA Damage/Telomere Stress Induced Senescence / potassium ion transport / CDK-mediated phosphorylation and removal of Cdc6 / Meiotic recombination / SCF(Skp2)-mediated degradation of p27/p21 / G2/M transition of mitotic cell cycle / Wnt signaling pathway / Orc1 removal from chromatin / Transcriptional regulation of granulopoiesis / Cyclin D associated events in G1 / kinase activity / cellular senescence / Regulation of TP53 Degradation / nuclear envelope / regulation of protein localization / Factors involved in megakaryocyte development and platelet production / Processing of DNA double-strand break ends / regulation of gene expression / Senescence-Associated Secretory Phenotype (SASP) / transcription regulator complex / Regulation of TP53 Activity through Phosphorylation / Ras protein signal transduction / chromosome, telomeric region / DNA replication / protein phosphorylation / endosome / chromatin remodeling / protein domain specific binding / cell division / protein serine kinase activity / DNA repair / protein serine/threonine kinase activity / positive regulation of cell population proliferation / DNA-templated transcription / centrosome / protein kinase binding / positive regulation of DNA-templated transcription / magnesium ion binding / negative regulation of transcription by RNA polymerase II / signal transduction / nucleoplasm / ATP binding / nucleus / cytoplasm / cytosol
Similarity search - Function
Cyclin, C-terminal domain / : / Cyclins signature. / Cyclin / Cyclin, C-terminal domain / Cyclin_C / Cyclin, N-terminal / Cyclin, N-terminal domain / Cyclin-like / domain present in cyclins, TFIIB and Retinoblastoma ...Cyclin, C-terminal domain / : / Cyclins signature. / Cyclin / Cyclin, C-terminal domain / Cyclin_C / 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-WZZ / G1/S-specific cyclin-E1 / Cyclin-dependent kinase 2
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 3 Å
AuthorsRen, X.
Funding support1items
OrganizationGrant numberCountry
Not funded
CitationJournal: Acs Med.Chem.Lett. / Year: 2023
Title: Accelerated Discovery of Macrocyclic CDK2 Inhibitor QR-6401 by Generative Models and Structure-Based Drug Design.
Authors: Yu, Y. / Huang, J. / He, H. / Han, J. / Ye, G. / Xu, T. / Sun, X. / Chen, X. / Ren, X. / Li, C. / Li, H. / Huang, W. / Liu, Y. / Wang, X. / Gao, Y. / Cheng, N. / Guo, N. / Chen, X. / Feng, J. ...Authors: Yu, Y. / Huang, J. / He, H. / Han, J. / Ye, G. / Xu, T. / Sun, X. / Chen, X. / Ren, X. / Li, C. / Li, H. / Huang, W. / Liu, Y. / Wang, X. / Gao, Y. / Cheng, N. / Guo, N. / Chen, X. / Feng, J. / Hua, Y. / Liu, C. / Zhu, G. / Xie, Z. / Yao, L. / Zhong, W. / Chen, X. / Liu, W. / Li, H.
History
DepositionOct 18, 2022Deposition site: PDBJ / Processing site: RCSB
Revision 1.0Feb 22, 2023Provider: repository / Type: Initial release
Revision 1.1Mar 29, 2023Group: Database references / Category: citation
Item: _citation.journal_volume / _citation.page_first ..._citation.journal_volume / _citation.page_first / _citation.page_last / _citation.pdbx_database_id_PubMed / _citation.title
Revision 1.2Sep 20, 2023Group: Data collection / Refinement description
Category: chem_comp_atom / chem_comp_bond / pdbx_initial_refinement_model
Item: _pdbx_initial_refinement_model.type
Revision 1.3Nov 20, 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 2
B: G1/S-specific cyclin-E1
hetero molecules


Theoretical massNumber of molelcules
Total (without water)66,0833
Polymers65,7532
Non-polymers3291
Water362
1


  • Idetical with deposited unit
  • defined by author&software
  • Evidence: gel filtration
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area3470 Å2
ΔGint-14 kcal/mol
Surface area24490 Å2
MethodPISA
Unit cell
Length a, b, c (Å)101.970, 101.970, 151.617
Angle α, β, γ (deg.)90.00, 90.00, 90.00
Int Tables number92
Space group name H-MP41212

-
Components

#1: Protein Cyclin-dependent kinase 2 / Cell division protein kinase 2 / p33 protein kinase


Mass: 34040.426 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: CDK2, CDKN2 / Production host: Escherichia coli (E. coli) / References: UniProt: P24941, cyclin-dependent kinase
#2: Protein G1/S-specific cyclin-E1


Mass: 31712.877 Da / Num. of mol.: 1 / Fragment: Residues 103-373
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: CCNE1, CCNE / Production host: Escherichia coli (E. coli) / References: UniProt: P24864
#3: Chemical ChemComp-WZZ / (1R,3S)-3-{3-[(pyridin-2-yl)amino]-1H-pyrazol-5-yl}cyclopentyl propan-2-ylcarbamate


Mass: 329.397 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C17H23N5O2 / Feature type: SUBJECT OF INVESTIGATION
#4: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 2 / Source method: isolated from a natural source / Formula: H2O
Has ligand of interestY
Has protein modificationY

-
Experimental details

-
Experiment

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

-
Sample preparation

CrystalDensity Matthews: 3 Å3/Da / Density % sol: 58.99 %
Crystal growTemperature: 291.15 K / Method: vapor diffusion, hanging drop / Details: 0.2 M sodium citrate pH 6.5, 10% PEG3350

-
Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: SSRF / Beamline: BL02U1 / Wavelength: 1 Å
DetectorType: DECTRIS EIGER2 S 9M / Detector: PIXEL / Date: Dec 15, 2021
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1 Å / Relative weight: 1
ReflectionResolution: 3→45.32 Å / Num. obs: 16618 / % possible obs: 97.91 % / Redundancy: 2 % / CC1/2: 1 / CC star: 1 / Rmerge(I) obs: 0.02245 / Rpim(I) all: 0.02245 / Rrim(I) all: 0.03175 / Net I/σ(I): 15.77
Reflection shellResolution: 3→3.107 Å / Rmerge(I) obs: 0.3028 / Mean I/σ(I) obs: 2.33 / Num. unique obs: 1612 / CC1/2: 0.894 / CC star: 0.972 / Rpim(I) all: 0.3028 / Rrim(I) all: 0.4283

-
Processing

Software
NameVersionClassification
SCALEPACKdata scaling
REFMAC5.8.0258refinement
PDB_EXTRACT3.27data extraction
HKL-2000data reduction
PHENIXphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 1W98

1w98


Resolution: 3→45.32 Å / Cor.coef. Fo:Fc: 0.922 / Cor.coef. Fo:Fc free: 0.766 / SU B: 31.511 / SU ML: 0.53 / Cross valid method: THROUGHOUT / ESU R Free: 0.602 / Stereochemistry target values: MAXIMUM LIKELIHOOD / Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS
RfactorNum. reflection% reflectionSelection details
Rfree0.35788 797 4.9 %RANDOM
Rwork0.24867 ---
obs0.25409 15514 98.08 %-
Solvent computationIon probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.2 Å / Solvent model: MASK
Displacement parametersBiso mean: 86.146 Å2
Baniso -1Baniso -2Baniso -3
1-4.58 Å2-0 Å2-0 Å2
2--4.58 Å2-0 Å2
3----9.16 Å2
Refinement stepCycle: 1 / Resolution: 3→45.32 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms4627 0 24 2 4653
Refine LS restraints
Refine-IDTypeDev idealDev ideal targetNumber
X-RAY DIFFRACTIONr_bond_refined_d0.0080.0134772
X-RAY DIFFRACTIONr_bond_other_d0.0010.0174517
X-RAY DIFFRACTIONr_angle_refined_deg1.6891.6446479
X-RAY DIFFRACTIONr_angle_other_deg1.1991.57710474
X-RAY DIFFRACTIONr_dihedral_angle_1_deg8.1375568
X-RAY DIFFRACTIONr_dihedral_angle_2_deg36.42122.415236
X-RAY DIFFRACTIONr_dihedral_angle_3_deg21.21715837
X-RAY DIFFRACTIONr_dihedral_angle_4_deg15.9261525
X-RAY DIFFRACTIONr_chiral_restr0.0710.2606
X-RAY DIFFRACTIONr_gen_planes_refined0.0070.025191
X-RAY DIFFRACTIONr_gen_planes_other0.0020.02996
X-RAY DIFFRACTIONr_nbd_refined
X-RAY DIFFRACTIONr_nbd_other
X-RAY DIFFRACTIONr_nbtor_refined
X-RAY DIFFRACTIONr_nbtor_other
X-RAY DIFFRACTIONr_xyhbond_nbd_refined
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_it8.7849.0942278
X-RAY DIFFRACTIONr_mcbond_other8.7719.0932277
X-RAY DIFFRACTIONr_mcangle_it13.0813.6082844
X-RAY DIFFRACTIONr_mcangle_other13.07913.612845
X-RAY DIFFRACTIONr_scbond_it7.7429.4732494
X-RAY DIFFRACTIONr_scbond_other7.7419.4722495
X-RAY DIFFRACTIONr_scangle_it
X-RAY DIFFRACTIONr_scangle_other11.85214.0523636
X-RAY DIFFRACTIONr_long_range_B_refined16.0855515
X-RAY DIFFRACTIONr_long_range_B_other16.0835516
X-RAY DIFFRACTIONr_rigid_bond_restr
X-RAY DIFFRACTIONr_sphericity_free
X-RAY DIFFRACTIONr_sphericity_bonded
LS refinement shellResolution: 3→3.078 Å / Total num. of bins used: 20
RfactorNum. reflection% reflection
Rfree0.399 43 -
Rwork0.35 1147 -
obs--99.5 %

+
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