[English] 日本語
Yorodumi
- PDB-2iw8: STRUCTURE OF HUMAN THR160-PHOSPHO CDK2-CYCLIN A F82H-L83V-H84D MU... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 2iw8
TitleSTRUCTURE OF HUMAN THR160-PHOSPHO CDK2-CYCLIN A F82H-L83V-H84D MUTANT WITH AN O6-CYCLOHEXYLMETHYLGUANINE INHIBITOR
Components
  • CELL DIVISION PROTEIN KINASE 2
  • CYCLIN-A2
KeywordsCELL CYCLE / PHOSPHORYLATION / NUCLEOTIDE-BINDING / SERINE/THREONINE-PROTEIN KINASE / CELL CYCLE COMPLEX / KINASE / MITOSIS / TRANSFERASE
Function / homology
Function and homology information


G2 Phase / Phosphorylation of proteins involved in the G2/M transition by Cyclin A:Cdc2 complexes / cyclin A2-CDK1 complex / cyclin A2-CDK2 complex / cell cycle G1/S phase transition / cellular response to luteinizing hormone stimulus / p53-Dependent G1 DNA Damage Response / mitotic cell cycle phase transition / Transcription of E2F targets under negative control by p107 (RBL1) and p130 (RBL2) in complex with HDAC1 / Regulation of APC/C activators between G1/S and early anaphase ...G2 Phase / Phosphorylation of proteins involved in the G2/M transition by Cyclin A:Cdc2 complexes / cyclin A2-CDK1 complex / cyclin A2-CDK2 complex / cell cycle G1/S phase transition / cellular response to luteinizing hormone stimulus / p53-Dependent G1 DNA Damage Response / mitotic cell cycle phase transition / Transcription of E2F targets under negative control by p107 (RBL1) and p130 (RBL2) in complex with HDAC1 / Regulation of APC/C activators between G1/S and early anaphase / cellular response to leptin stimulus / male pronucleus / Telomere Extension By Telomerase / G0 and Early G1 / female pronucleus / response to glucagon / cellular response to cocaine / cellular response to nitric oxide / cyclin-dependent protein serine/threonine kinase regulator activity / cellular response to insulin-like growth factor stimulus / positive regulation of DNA biosynthetic process / TP53 Regulates Transcription of Genes Involved in G1 Cell Cycle Arrest / cochlea development / cellular response to platelet-derived growth factor stimulus / 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 / regulation of DNA replication / animal organ regeneration / post-translational protein modification / cellular response to estradiol stimulus / DNA Damage/Telomere Stress Induced Senescence / CDK-mediated phosphorylation and removal of Cdc6 / Cdc20:Phospho-APC/C mediated degradation of Cyclin A / SCF(Skp2)-mediated degradation of p27/p21 / Orc1 removal from chromatin / G1/S transition of mitotic cell cycle / G2/M transition of mitotic cell cycle / positive regulation of fibroblast proliferation / Regulation of TP53 Degradation / Processing of DNA double-strand break ends / Senescence-Associated Secretory Phenotype (SASP) / cellular response to hypoxia / Regulation of TP53 Activity through Phosphorylation / Ras protein signal transduction / Ub-specific processing proteases / protein domain specific binding / cell division / centrosome / DNA-templated transcription / positive regulation of DNA-templated transcription / protein kinase binding / nucleoplasm / nucleus / cytoplasm / cytosol
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 / Replication initiator protein RctB, central region / RctB, helix turn helix domain / Vibrionales, replication initiator protein RctB, central region / RctB helix turn helix 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 / Protein kinase domain / 2-Layer Sandwich / Orthogonal Bundle / Mainly Alpha / Alpha Beta
Similarity search - Domain/homology
Chem-4SP / MONOTHIOGLYCEROL / Cyclin-A2 / Uncharacterized protein
Similarity search - Component
Biological speciesHOMO SAPIENS (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.3 Å
AuthorsPratt, D.J. / Bentley, J. / Jewsbury, P. / Boyle, F.T. / Endicott, J.A. / Noble, M.E.M.
CitationJournal: J.Med.Chem. / Year: 2006
Title: Dissecting the Determinants of Cyclin-Dependent Kinase 2 and Cyclin-Dependent Kinase 4 Inhibitor Selectivity.
Authors: Pratt, D.J. / Bentley, J. / Jewsbury, P. / Boyle, F.T. / Endicott, J.A. / Noble, M.E.M.
History
DepositionJun 27, 2006Deposition site: PDBE / Processing site: PDBE
Revision 1.0Sep 6, 2006Provider: repository / Type: Initial release
Revision 1.1Jul 13, 2011Group: Advisory / Version format compliance
Revision 1.2Dec 13, 2023Group: Data collection / Database references ...Data collection / Database references / Derived calculations / Other / Refinement description
Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / database_2 / pdbx_database_status / pdbx_initial_refinement_model / struct_conn
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.pdbx_leaving_atom_flag

-
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)129,4088
Polymers128,3874
Non-polymers1,0214
Water5,567309
1
A: CELL DIVISION PROTEIN KINASE 2
B: CYCLIN-A2
hetero molecules


Theoretical massNumber of molelcules
Total (without water)64,7044
Polymers64,1932
Non-polymers5112
Water362
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area4310 Å2
ΔGint-20.2 kcal/mol
Surface area22950 Å2
MethodPISA
2
C: CELL DIVISION PROTEIN KINASE 2
D: CYCLIN-A2
hetero molecules


Theoretical massNumber of molelcules
Total (without water)64,7044
Polymers64,1932
Non-polymers5112
Water362
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area4220 Å2
ΔGint-20.8 kcal/mol
Surface area22080 Å2
MethodPISA
Unit cell
Length a, b, c (Å)73.894, 135.324, 148.323
Angle α, β, γ (deg.)90.00, 90.00, 90.00
Int Tables number19
Space group name H-MP212121
Noncrystallographic symmetry (NCS)NCS domain:
IDEns-IDDetails
11A
21C
12B
22D

NCS domain segments:
Dom-IDComponent-IDEns-IDRefine codeAuth asym-IDAuth seq-ID
1114A0 - 298
2114C0 - 298
1124B175 - 432
2124D175 - 432

NCS ensembles :
ID
1
2

-
Components

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


Mass: 34308.652 Da / Num. of mol.: 2 / Mutation: YES
Source method: isolated from a genetically manipulated source
Details: PHOSPHOTHREONINE 160 / Source: (gene. exp.) HOMO SAPIENS (human) / Description: WILD TYPE GENE WAS A GIFT FROM DR D.O.MORGAN / Plasmid: PGEX 6P-1 / Production host: ESCHERICHIA COLI (E. coli) / Strain (production host): BL21(DE3) / References: UniProt: P24941, EC: 2.7.1.37
#2: Protein CYCLIN-A2 / HUMAN CYCLIN A / CYCLIN-A


Mass: 29884.605 Da / Num. of mol.: 2 / Fragment: A3, RESIDUES 174-432
Source method: isolated from a genetically manipulated source
Details: MONOTHIOGLYCEROL ADDUCT ON RESIDUE 193 / Source: (gene. exp.) HOMO SAPIENS (human)
Description: FULL LENGTH CYCLIN A WAS A GIFT FROM DR M.DOREE
Plasmid: PET21D / Production host: ESCHERICHIA COLI (E. coli) / Strain (production host): BL21(DE3) / References: UniProt: P20248
#3: Chemical ChemComp-4SP / O6-CYCLOHEXYLMETHOXY-2-(4'-SULPHAMOYLANILINO) PURINE


Mass: 402.471 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C18H22N6O3S
#4: Chemical ChemComp-SGM / MONOTHIOGLYCEROL


Mass: 108.159 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C3H8O2S
#5: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 309 / Source method: isolated from a natural source / Formula: H2O
Compound detailsENGINEERED RESIDUE IN CHAIN A, PHE 82 TO HIS ENGINEERED RESIDUE IN CHAIN A, LEU 83 TO VAL ...ENGINEERED RESIDUE IN CHAIN A, PHE 82 TO HIS ENGINEERED RESIDUE IN CHAIN A, LEU 83 TO VAL ENGINEERED RESIDUE IN CHAIN A, HIS 84 TO ASP ENGINEERED RESIDUE IN CHAIN C, PHE 82 TO HIS ENGINEERED RESIDUE IN CHAIN C, LEU 83 TO VAL ENGINEERED RESIDUE IN CHAIN C, HIS 84 TO ASP
Sequence detailsGPGS INTRODUCED AT N-TERMINUS BY CLONING. M INTRODUCED AT N-TERMINUS BY CLONING.

-
Experimental details

-
Experiment

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

-
Sample preparation

CrystalDensity Matthews: 2.93 Å3/Da / Density % sol: 57.75 %
Crystal growpH: 7
Details: DROPLET CONTAINED PROTEIN AT A CONCENTRATION OF 10 MG ML-1 IN 40 MM HEPES PH 7.0 CONTAINING 1 MM DTT, 200 MM NACL, 5% V/V DMSO AND 1MM INHIBITOR. THE RESERVOIR SOLUTION CONTAINED 0.8 M KCL ...Details: DROPLET CONTAINED PROTEIN AT A CONCENTRATION OF 10 MG ML-1 IN 40 MM HEPES PH 7.0 CONTAINING 1 MM DTT, 200 MM NACL, 5% V/V DMSO AND 1MM INHIBITOR. THE RESERVOIR SOLUTION CONTAINED 0.8 M KCL AND 1.2 M (NH4)2SO4 IN 40 MM HEPES PH 7.0 AND 5 MM DTT.

-
Data collection

DiffractionMean temperature: 100 K
Diffraction sourceSource: SYNCHROTRON / Site: ESRF / Beamline: ID14-2 / Wavelength: 0.933
DetectorType: ADSC CCD / Detector: CCD / Date: Nov 21, 2002
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.933 Å / Relative weight: 1
ReflectionResolution: 2.3→65.9 Å / Num. obs: 64531 / % possible obs: 97.1 % / Observed criterion σ(I): 0 / Redundancy: 2.6 % / Rmerge(I) obs: 0.13 / Net I/σ(I): 3.6
Reflection shellResolution: 2.3→2.41 Å / Redundancy: 2.5 % / Rmerge(I) obs: 0.32 / Mean I/σ(I) obs: 2.3 / % possible all: 94.4

-
Processing

Software
NameVersionClassification
REFMAC5.2.0019refinement
MOSFLMdata reduction
SCALAdata scaling
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: PDB ENTRY 1H1S

1h1s


Resolution: 2.3→100 Å / Cor.coef. Fo:Fc: 0.928 / Cor.coef. Fo:Fc free: 0.895 / SU B: 14.391 / SU ML: 0.164 / TLS residual ADP flag: LIKELY RESIDUAL / Cross valid method: THROUGHOUT / ESU R: 0.301 / ESU R Free: 0.231 / Stereochemistry target values: MAXIMUM LIKELIHOOD / Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS.
RfactorNum. reflection% reflectionSelection details
Rfree0.255 3271 5.1 %RANDOM
Rwork0.212 ---
obs0.214 61234 96.5 %-
Solvent computationIon probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.4 Å / Solvent model: MASK
Displacement parametersBiso mean: 14.38 Å2
Baniso -1Baniso -2Baniso -3
1--1.25 Å20 Å20 Å2
2--0.73 Å20 Å2
3---0.52 Å2
Refinement stepCycle: LAST / Resolution: 2.3→100 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms8646 0 68 309 9023
Refine LS restraints
Refine-IDTypeDev idealDev ideal targetNumber
X-RAY DIFFRACTIONr_bond_refined_d0.0120.0228929
X-RAY DIFFRACTIONr_bond_other_d
X-RAY DIFFRACTIONr_angle_refined_deg1.4091.98712118
X-RAY DIFFRACTIONr_angle_other_deg
X-RAY DIFFRACTIONr_dihedral_angle_1_deg5.9151068
X-RAY DIFFRACTIONr_dihedral_angle_2_deg41.32723.953382
X-RAY DIFFRACTIONr_dihedral_angle_3_deg16.99151574
X-RAY DIFFRACTIONr_dihedral_angle_4_deg17.6181544
X-RAY DIFFRACTIONr_chiral_restr0.0920.21376
X-RAY DIFFRACTIONr_gen_planes_refined0.0050.026590
X-RAY DIFFRACTIONr_gen_planes_other
X-RAY DIFFRACTIONr_nbd_refined0.2040.24185
X-RAY DIFFRACTIONr_nbd_other
X-RAY DIFFRACTIONr_nbtor_refined0.3020.26053
X-RAY DIFFRACTIONr_nbtor_other
X-RAY DIFFRACTIONr_xyhbond_nbd_refined0.1870.2441
X-RAY DIFFRACTIONr_xyhbond_nbd_other
X-RAY DIFFRACTIONr_metal_ion_refined
X-RAY DIFFRACTIONr_metal_ion_other
X-RAY DIFFRACTIONr_symmetry_vdw_refined0.2210.248
X-RAY DIFFRACTIONr_symmetry_vdw_other
X-RAY DIFFRACTIONr_symmetry_hbond_refined0.1750.28
X-RAY DIFFRACTIONr_symmetry_hbond_other
X-RAY DIFFRACTIONr_symmetry_metal_ion_refined
X-RAY DIFFRACTIONr_symmetry_metal_ion_other
X-RAY DIFFRACTIONr_mcbond_it0.691.55540
X-RAY DIFFRACTIONr_mcbond_other
X-RAY DIFFRACTIONr_mcangle_it1.13428734
X-RAY DIFFRACTIONr_mcangle_other
X-RAY DIFFRACTIONr_scbond_it1.73133868
X-RAY DIFFRACTIONr_scbond_other
X-RAY DIFFRACTIONr_scangle_it2.6474.53384
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
Refine LS restraints NCS

Refine-ID: X-RAY DIFFRACTION

Ens-IDDom-IDAuth asym-IDNumberTypeRms dev position (Å)Weight position
11A2126medium positional0.420.5
12C2126medium positional0.420.5
21B2045medium positional0.280.5
22D2045medium positional0.280.5
11A2126medium thermal0.952
12C2126medium thermal0.952
21B2045medium thermal0.712
22D2045medium thermal0.712
LS refinement shellResolution: 2.3→2.36 Å / Total num. of bins used: 20 /
RfactorNum. reflection
Rfree0.312 234
Rwork0.235 4306
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)
11.00740.3736-0.21210.8287-0.20030.7790.03250.03710.0045-0.1097-0.0040.0793-0.0504-0.074-0.0284-0.170.02-0.0066-0.15520.0043-0.15288.462643.047464.2985
21.1909-0.23940.37981.6097-0.12391.7914-0.0485-0.10010.09990.06930.0566-0.0555-0.2119-0.0066-0.008-0.1389-0.01360.0287-0.1661-0.0303-0.157322.109767.667377.5917
31.45470.2415-0.61331.6343-0.22651.39350.05960.01210.10720.1547-0.1449-0.1769-0.23670.39850.08540.0609-0.1034-0.06450.15630.132-0.032344.422781.619542.6702
42.7590.4250.16562.2336-0.25251.06750.08050.1825-0.44140.0331-0.12-0.56730.23050.53010.03950.05780.1716-0.00750.18980.040.061844.823248.497939.0209
Refinement TLS group
IDRefine-IDRefine TLS-IDAuth asym-IDAuth seq-ID
1X-RAY DIFFRACTION1A0 - 298
2X-RAY DIFFRACTION1A1298
3X-RAY DIFFRACTION2B175 - 432
4X-RAY DIFFRACTION3C0 - 298
5X-RAY DIFFRACTION3C1297
6X-RAY DIFFRACTION4D175 - 432

+
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://pdbjlvh1.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