[English] 日本語
Yorodumi
- PDB-1vyw: Structure of CDK2/Cyclin A with PNU-292137 -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 1vyw
TitleStructure of CDK2/Cyclin A with PNU-292137
Components
  • CELL DIVISION PROTEIN KINASE 2
  • CYCLIN A2
KeywordsTRANSFERASE / TRANSFERASE-COMPLEX / PROTEIN KINASE-COMPLEX / PROTEIN KINASE / SERINE/THREONINE-PROTEIN KINASE / PHOSPHORYLATION / CELL DIVISION / CYCLIN
Function / homology
Function and homology information


Phosphorylation of proteins involved in the G2/M transition by Cyclin A:Cdc2 complexes / cyclin A2-CDK1 complex / cell cycle G1/S phase transition / cellular response to luteinizing hormone stimulus / mitotic cell cycle phase transition / Transcription of E2F targets under negative control by p107 (RBL1) and p130 (RBL2) in complex with HDAC1 / cellular response to leptin stimulus / male pronucleus / female pronucleus / response to glucagon ...Phosphorylation of proteins involved in the G2/M transition by Cyclin A:Cdc2 complexes / cyclin A2-CDK1 complex / cell cycle G1/S phase transition / cellular response to luteinizing hormone stimulus / mitotic cell cycle phase transition / Transcription of E2F targets under negative control by p107 (RBL1) and p130 (RBL2) in complex with HDAC1 / cellular response to leptin stimulus / male pronucleus / female pronucleus / response to glucagon / cellular response to cocaine / cyclin-dependent protein serine/threonine kinase regulator activity / cellular response to insulin-like growth factor stimulus / positive regulation of DNA biosynthetic process / cochlea development / cyclin A1-CDK2 complex / cyclin E2-CDK2 complex / cyclin E1-CDK2 complex / cellular response to platelet-derived growth factor stimulus / cyclin A2-CDK2 complex / positive regulation of DNA-templated DNA replication initiation / G2 Phase / cyclin-dependent protein kinase activity / Y chromosome / 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 / PTK6 Regulates Cell Cycle / regulation of anaphase-promoting complex-dependent catabolic process / regulation of DNA replication / Defective binding of RB1 mutants to E2F1,(E2F2, E2F3) / centriole replication / Regulation of APC/C activators between G1/S and early anaphase / centrosome duplication / Telomere Extension By Telomerase / G0 and Early G1 / Activation of the pre-replicative complex / cyclin-dependent protein kinase holoenzyme complex / cellular response to nitric oxide / Cajal body / animal organ regeneration / cyclin-dependent kinase / cyclin-dependent protein serine/threonine kinase activity / Activation of ATR in response to replication stress / TP53 Regulates Transcription of Genes Involved in G1 Cell Cycle Arrest / 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 / condensed chromosome / mitotic G1 DNA damage checkpoint signaling / regulation of G2/M transition of mitotic cell cycle / cyclin binding / post-translational protein modification / meiotic cell cycle / male germ cell nucleus / response to organic substance / cellular response to estradiol stimulus / Cdc20:Phospho-APC/C mediated degradation of Cyclin A / G1/S transition of mitotic cell cycle / potassium ion transport / DNA Damage/Telomere Stress Induced Senescence / CDK-mediated phosphorylation and removal of Cdc6 / SCF(Skp2)-mediated degradation of p27/p21 / Meiotic recombination / Orc1 removal from chromatin / Transcriptional regulation of granulopoiesis / Cyclin D associated events in G1 / positive regulation of fibroblast proliferation / G2/M transition of mitotic cell cycle / cellular senescence / Regulation of TP53 Degradation / nuclear envelope / Factors involved in megakaryocyte development and platelet production / Processing of DNA double-strand break ends / cellular response to hypoxia / Senescence-Associated Secretory Phenotype (SASP) / regulation of gene expression / peptidyl-serine phosphorylation / Ras protein signal transduction / Regulation of TP53 Activity through Phosphorylation / transcription regulator complex / DNA replication / chromosome, telomeric region / Ub-specific processing proteases / endosome / chromatin remodeling / cell division / protein domain specific binding / protein phosphorylation / DNA repair / protein serine kinase activity / centrosome / protein serine/threonine kinase activity / DNA-templated transcription / positive regulation of cell population proliferation / protein kinase binding / positive regulation of DNA-templated transcription / magnesium ion binding / negative regulation of transcription by RNA polymerase II
Similarity search - Function
Cyclin-A, N-terminal APC/C binding region / Cyclin-A N-terminal APC/C binding region / : / Cyclin, C-terminal domain / : / Cyclins signature. / Cyclin / Cyclin, C-terminal domain / Cyclin_C / Cyclin-like ...Cyclin-A, N-terminal APC/C binding region / Cyclin-A N-terminal APC/C binding region / : / Cyclin, C-terminal domain / : / Cyclins signature. / Cyclin / Cyclin, C-terminal domain / Cyclin_C / 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-292 / Cyclin-A2 / Cyclin-dependent kinase 2
Similarity search - Component
Biological speciesHOMO SAPIENS (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / OTHER / Resolution: 2.3 Å
AuthorsPevarello, P. / Brasca, M.G. / Amici, R. / Orsini, P. / Traquandi, G. / Corti, L. / Piutti, C. / Sansonna, P. / Villa, M. / Pierce, B.S. ...Pevarello, P. / Brasca, M.G. / Amici, R. / Orsini, P. / Traquandi, G. / Corti, L. / Piutti, C. / Sansonna, P. / Villa, M. / Pierce, B.S. / Pulici, M. / Giordano, P. / Martina, K. / Fritzen, E.L. / Nugent, R.A. / Casale, E. / Cameron, A. / Ciomei, M. / Roletto, F. / Isacchi, A. / Fogliatto, G. / Pesenti, E. / Pastori, W. / Marsiglio, A. / Leach, K.L. / Clare, P.M. / Fiorentini, F. / Varasi, M. / Vulpetti, A. / Warpehoski, M.A.
CitationJournal: J.Med.Chem. / Year: 2004
Title: 3-Aminopyrazole Inhibitors of Cdk2/Cyclin a as Antitumor Agents. Part 1. Lead Finding
Authors: Pevarello, P. / Brasca, M.G. / Amici, R. / Orsini, P. / Traquandi, G. / Corti, L. / Piutti, C. / Sansonna, P. / Villa, M. / Pierce, B.S. / Pulici, M. / Giordano, P. / Martina, K. / Fritzen, ...Authors: Pevarello, P. / Brasca, M.G. / Amici, R. / Orsini, P. / Traquandi, G. / Corti, L. / Piutti, C. / Sansonna, P. / Villa, M. / Pierce, B.S. / Pulici, M. / Giordano, P. / Martina, K. / Fritzen, E.L. / Nugent, R.A. / Casale, E. / Cameron, A. / Ciomei, M. / Roletto, F. / Isacchi, A. / Fogliatto, G. / Pesenti, E. / Pastori, W. / Marsiglio, A. / Leach, K.L. / Clare, P.M. / Fiorentini, F. / Varasi, M. / Vulpetti, A. / Warpehoski, M.A.
History
DepositionMay 7, 2004Deposition site: PDBE / Processing site: PDBE
Revision 1.0Jun 10, 2004Provider: repository / Type: Initial release
Revision 1.1May 8, 2011Group: Version format compliance
Revision 1.2Jul 13, 2011Group: Version format compliance
Revision 1.3Apr 3, 2019Group: Data collection / Other / Source and taxonomy
Category: entity_src_gen / pdbx_database_proc / pdbx_database_status
Item: _entity_src_gen.pdbx_host_org_cell_line / _entity_src_gen.pdbx_host_org_scientific_name ..._entity_src_gen.pdbx_host_org_cell_line / _entity_src_gen.pdbx_host_org_scientific_name / _entity_src_gen.pdbx_host_org_strain / _pdbx_database_status.recvd_author_approval

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: CELL DIVISION PROTEIN KINASE 2
B: CYCLIN A2
C: CELL DIVISION PROTEIN KINASE 2
D: CYCLIN A2
hetero molecules


Theoretical massNumber of molelcules
Total (without water)131,8378
Polymers131,0624
Non-polymers7754
Water7,386410
1
A: CELL DIVISION PROTEIN KINASE 2
B: CYCLIN A2
hetero molecules


Theoretical massNumber of molelcules
Total (without water)65,9184
Polymers65,5312
Non-polymers3872
Water362
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area3880 Å2
ΔGint-20 kcal/mol
Surface area23680 Å2
MethodPISA
2
C: CELL DIVISION PROTEIN KINASE 2
D: CYCLIN A2
hetero molecules


Theoretical massNumber of molelcules
Total (without water)65,9184
Polymers65,5312
Non-polymers3872
Water362
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area3890 Å2
ΔGint-21 kcal/mol
Surface area23570 Å2
MethodPISA
Unit cell
Length a, b, c (Å)184.223, 184.223, 214.720
Angle α, β, γ (deg.)90.00, 90.00, 120.00
Int Tables number180
Space group name H-MP6222
Noncrystallographic symmetry (NCS)NCS oper:
IDCodeMatrixVector
1given(-0.23592, -0.87854, 0.41533), (-0.87121, 0.00188, -0.49091), (0.4305, -0.47766, -0.76584)95.81634, 216.77879, 275.58487
2given(-0.25951, -0.85849, 0.44233), (-0.86401, 0.00177, -0.50348), (0.43145, -0.51283, -0.7422)88.10458, 218.2545, 279.97919

-
Components

#1: Protein CELL DIVISION PROTEIN KINASE 2 / / P33 PROTEIN KINASE


Mass: 35251.883 Da / Num. of mol.: 2
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) HOMO SAPIENS (human) / Cell line (production host): High Five / Production host: SPODOPTERA FRUGIPERDA (fall armyworm) / References: UniProt: P24941, EC: 2.7.1.37
#2: Protein CYCLIN A2 / / CYCLIN A


Mass: 30278.967 Da / Num. of mol.: 2 / Fragment: C-TERMINAL PORTION, RESIDUES 174-432
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) HOMO SAPIENS (human) / Plasmid: PGEX6P / Production host: ESCHERICHIA COLI BL21 (bacteria) / References: UniProt: P20248
#3: Chemical ChemComp-SO4 / SULFATE ION / Sulfate


Mass: 96.063 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: SO4
#4: Chemical ChemComp-292 / N-(3-CYCLOPROPYL-1H-PYRAZOL-5-YL)-2-(2-NAPHTHYL)ACETAMIDE / PNU-292137 INHIBITOR


Mass: 291.347 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C18H17N3O
#5: Water ChemComp-HOH / water / Water


Mass: 18.015 Da / Num. of mol.: 410 / Source method: isolated from a natural source / Formula: H2O
Compound detailsCDK KINASE IS PROBABLY INVOLVED IN THE CONTROL OF THE CELL CYCLE. INTERACTS WITH CYCLINS A, D, OR E. ...CDK KINASE IS PROBABLY INVOLVED IN THE CONTROL OF THE CELL CYCLE. INTERACTS WITH CYCLINS A, D, OR E. ACTIVITY OF CDK2 IS MAXIMAL DURING S PHASE AND G2. CYCLIN A2 IS ESSENTIAL FOR THE CONTROL OF THE CELL CYCLE AT THE G1/S (START) AND THE G2/M (MITOSIS) TRANSITIONS.
Sequence details5 AMINO ACIDS EXTRA AT THE N-TERMINUS RESIDUES 174-432, CHAINS B AND D

-
Experimental details

-
Experiment

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

-
Sample preparation

CrystalDensity Matthews: 4 Å3/Da / Density % sol: 64 %
Crystal growpH: 7 / Details: 20% AMMONIUM SULPHATE, 1M KCL, 40MM HEPES PH 7

-
Data collection

DiffractionMean temperature: 100 K
Diffraction sourceSource: SYNCHROTRON / Site: ESRF / Beamline: ID14-2 / Wavelength: 0.934
DetectorType: ADSC CCD / Detector: CCD / Date: Nov 20, 2003
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.934 Å / Relative weight: 1
ReflectionResolution: 2.3→35 Å / Num. obs: 94577 / % possible obs: 99 % / Redundancy: 4.8 % / Biso Wilson estimate: 36.5 Å2 / Rmerge(I) obs: 0.081 / Net I/σ(I): 16
Reflection shellResolution: 2.3→2.38 Å / Redundancy: 4.2 % / Rmerge(I) obs: 0.69 / Mean I/σ(I) obs: 2.3 / % possible all: 97

-
Processing

Software
NameVersionClassification
CNX2002refinement
DENZOdata reduction
SCALEPACKdata scaling
CNXphasing
RefinementMethod to determine structure: OTHER / Resolution: 2.3→29.86 Å / Rfactor Rfree error: 0.006 / Isotropic thermal model: RESTRAINED / Cross valid method: THROUGHOUT / σ(F): 0
Details: BULK SOLVENT MODEL USED. THERE IS A FEATURE IN THE ELECTRON DENSITY MAP ATTACHED TO ASP 28 OF BOTH CDK2 MOLECULES THAT COULD NOT BE ASSIGNED TO ANY MOLECULE IN THE CRYSTALLISATION MIXTURE. ...Details: BULK SOLVENT MODEL USED. THERE IS A FEATURE IN THE ELECTRON DENSITY MAP ATTACHED TO ASP 28 OF BOTH CDK2 MOLECULES THAT COULD NOT BE ASSIGNED TO ANY MOLECULE IN THE CRYSTALLISATION MIXTURE. THIS HAS BEEN MODELLED BY WATER MOLECULES.
RfactorNum. reflection% reflectionSelection details
Rfree0.258 1908 2 %RANDOM
Rwork0.229 ---
obs-94195 99 %-
Solvent computationSolvent model: FLAT MODEL / Bsol: 39.4784 Å2 / ksol: 0.342118 e/Å3
Displacement parametersBiso mean: 47.6 Å2
Baniso -1Baniso -2Baniso -3
1-5.48 Å29.08 Å20 Å2
2--5.48 Å20 Å2
3----10.96 Å2
Refine analyze
FreeObs
Luzzati coordinate error0.36 Å0.32 Å
Luzzati d res low-5 Å
Luzzati sigma a0.34 Å0.33 Å
Refinement stepCycle: LAST / Resolution: 2.3→29.86 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms8978 0 54 410 9442
Refine LS restraints
Refine-IDTypeDev ideal
X-RAY DIFFRACTIONc_bond_d0.007
X-RAY DIFFRACTIONc_bond_d_na
X-RAY DIFFRACTIONc_bond_d_prot
X-RAY DIFFRACTIONc_angle_d
X-RAY DIFFRACTIONc_angle_d_na
X-RAY DIFFRACTIONc_angle_d_prot
X-RAY DIFFRACTIONc_angle_deg1.2
X-RAY DIFFRACTIONc_angle_deg_na
X-RAY DIFFRACTIONc_angle_deg_prot
X-RAY DIFFRACTIONc_dihedral_angle_d20.8
X-RAY DIFFRACTIONc_dihedral_angle_d_na
X-RAY DIFFRACTIONc_dihedral_angle_d_prot
X-RAY DIFFRACTIONc_improper_angle_d0.82
X-RAY DIFFRACTIONc_improper_angle_d_na
X-RAY DIFFRACTIONc_improper_angle_d_prot
X-RAY DIFFRACTIONc_mcbond_it
X-RAY DIFFRACTIONc_mcangle_it
X-RAY DIFFRACTIONc_scbond_it
X-RAY DIFFRACTIONc_scangle_it
LS refinement shellResolution: 2.3→2.44 Å / Rfactor Rfree error: 0.019 / Total num. of bins used: 6
RfactorNum. reflection% reflection
Rfree0.328 308 2 %
Rwork0.303 14771 -
obs--96.5 %
Xplor file
Refine-IDSerial noParam fileTopol file
X-RAY DIFFRACTION1PROTEINPROTEIN
X-RAY DIFFRACTION2ION.PARION.TOP
X-RAY DIFFRACTION3WATER_RWATER.T
X-RAY DIFFRACTION4PNU-292137.PARPNU-292137.TOP

+
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