[English] 日本語
Yorodumi
- PDB-3pj8: Structure of CDK2 in complex with a Pyrazolo[4,3-d]pyrimidine Bio... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 3pj8
TitleStructure of CDK2 in complex with a Pyrazolo[4,3-d]pyrimidine Bioisostere of Roscovitine.
ComponentsCell division protein kinase 2
KeywordsTRANSFERASE/TRANSFERASE INHIBITOR / PHOSPHORYLATION / CELL DIVISION / MITOSIS / Cyclin / TRANSFERASE-TRANSFERASE INHIBITOR complex
Function / homology
Function and homology information


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 / 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 ...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 / 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 / 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 / centrosome duplication / G0 and Early G1 / Telomere Extension By Telomerase / Activation of the pre-replicative complex / cellular response to nitric oxide / Regulation of MITF-M-dependent genes involved in cell cycle and proliferation / cyclin-dependent kinase / cyclin-dependent protein serine/threonine kinase activity / TP53 Regulates Transcription of Genes Involved in G1 Cell Cycle Arrest / 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 / Cajal body / cyclin-dependent protein kinase holoenzyme complex / Cyclin A:Cdk2-associated events at S phase entry / condensed chromosome / mitotic G1 DNA damage checkpoint signaling / regulation of mitotic cell cycle / regulation of G2/M transition of mitotic cell cycle / : / cyclin binding / post-translational protein modification / positive regulation of DNA replication / meiotic cell cycle / male germ cell nucleus / 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 / G1/S transition of mitotic cell cycle / Cyclin D associated events in G1 / 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 / Senescence-Associated Secretory Phenotype (SASP) / regulation of gene expression / peptidyl-serine phosphorylation / DNA replication / Ras protein signal transduction / Regulation of TP53 Activity through Phosphorylation / transcription regulator complex / chromosome, telomeric region / endosome / chromatin remodeling / protein domain specific binding / cell division / protein phosphorylation / DNA repair / protein serine kinase activity / protein serine/threonine kinase activity / centrosome / DNA-templated transcription / positive regulation of cell population proliferation / positive regulation of DNA-templated transcription / negative regulation of transcription by RNA polymerase II / magnesium ion binding / signal transduction / nucleoplasm / ATP binding / nucleus / cytosol / cytoplasm
Similarity search - Function
: / 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 ...: / 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-404 / Cyclin-dependent kinase 2
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / MOLECULAR REPLACEMENT / Resolution: 1.96 Å
AuthorsMcNae, I.W. / Jorda, R. / Havlicek, L. / Strnad, M. / Voller, J. / Walkinshaw, M.D. / Krystof, V.
CitationJournal: J.Med.Chem. / Year: 2011
Title: Pyrazolo[4,3-d]pyrimidine Bioisostere of Roscovitine: Evaluation of a Novel Selective Inhibitor of Cyclin-Dependent Kinases with Antiproliferative Activity.
Authors: Jorda, R. / McNae, I.W. / Walkinshaw, M.D. / Voller, J. / Navratilova, J. / Kuzma, M. / Mistrik, M. / Bartek, J. / Strnad, M.
History
DepositionNov 9, 2010Deposition site: RCSB / Processing site: RCSB
Revision 1.0Apr 6, 2011Provider: repository / Type: Initial release
Revision 1.1Jul 13, 2011Group: Version format compliance
Revision 1.2Feb 21, 2024Group: Data collection / Database references / Derived calculations
Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / database_2 / struct_ref_seq_dif / struct_site
Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession ..._database_2.pdbx_DOI / _database_2.pdbx_database_accession / _struct_ref_seq_dif.details / _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: Cell division protein kinase 2
hetero molecules


Theoretical massNumber of molelcules
Total (without water)34,3882
Polymers34,0341
Non-polymers3541
Water2,630146
1


  • Idetical with deposited unit
  • defined by author&software
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
MethodPISA
Unit cell
Length a, b, c (Å)54.350, 71.890, 72.480
Angle α, β, γ (deg.)90.00, 90.00, 90.00
Int Tables number19
Space group name H-MP212121

-
Components

#1: Protein Cell division protein kinase 2 / p33 protein kinase


Mass: 34033.543 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: CDK2 / Production host: Escherichia coli (E. coli) / References: UniProt: P24941, cyclin-dependent kinase
#2: Chemical ChemComp-404 / (2R)-2-{[7-(benzylamino)-3-(propan-2-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]amino}butan-1-ol


Mass: 354.449 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C19H26N6O
#3: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 146 / Source method: isolated from a natural source / Formula: H2O

-
Experimental details

-
Experiment

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

-
Sample preparation

CrystalDensity Matthews: 2.08 Å3/Da / Density % sol: 40.87 %
Crystal growTemperature: 290 K / Method: vapor diffusion, hanging drop / pH: 8
Details: PEG 3350, Na-HEPES, pH 8, VAPOR DIFFUSION, HANGING DROP, temperature 290K

-
Data collection

DiffractionMean temperature: 100 K
Diffraction sourceSource: ROTATING ANODE / Type: RIGAKU MICROMAX-007 HF / Wavelength: 1.5418 Å
DetectorType: MAR scanner 345 mm plate / Detector: IMAGE PLATE / Date: May 27, 2009 / Details: mirrors
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1.5418 Å / Relative weight: 1
ReflectionResolution: 1.96→21.1 Å / Num. obs: 18832 / % possible obs: 89.6 % / Observed criterion σ(F): 2 / Observed criterion σ(I): 2 / Redundancy: 6.7 % / Rmerge(I) obs: 0.063 / Net I/σ(I): 17.7
Reflection shellResolution: 1.96→2.07 Å / Redundancy: 6.5 % / Rmerge(I) obs: 0.242 / Mean I/σ(I) obs: 7 / Num. unique all: 3005 / % possible all: 99.9

-
Processing

Software
NameVersionClassification
MAR345dtbdata collection
PHASERphasing
PHENIX(phenix.refine: 1.6.2_432)refinement
MOSFLMdata reduction
SCALAdata scaling
RefinementMethod to determine structure: MOLECULAR REPLACEMENT / Resolution: 1.96→21.1 Å / SU ML: 0.3 / σ(F): 1.34 / Stereochemistry target values: ML
RfactorNum. reflection% reflectionSelection details
Rfree0.2733 954 5.09 %RANDOM
Rwork0.2022 ---
obs0.2057 18755 89.47 %-
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT BULK SOLVENT MODEL / Bsol: 36.67 Å2 / ksol: 0.339 e/Å3
Displacement parameters
Baniso -1Baniso -2Baniso -3
1--0.9945 Å2-0 Å20 Å2
2---2.7367 Å2-0 Å2
3---3.7312 Å2
Refinement stepCycle: LAST / Resolution: 1.96→21.1 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms2303 0 26 146 2475
Refine LS restraints
Refine-IDTypeDev idealNumber
X-RAY DIFFRACTIONf_bond_d0.0062397
X-RAY DIFFRACTIONf_angle_d1.0353248
X-RAY DIFFRACTIONf_dihedral_angle_d15.84892
X-RAY DIFFRACTIONf_chiral_restr0.063363
X-RAY DIFFRACTIONf_plane_restr0.004407
LS refinement shell
Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkRefine-ID% reflection obs (%)
1.96-2.06330.33951500.23632777X-RAY DIFFRACTION100
2.0633-2.19250.33851210.20992328X-RAY DIFFRACTION84
2.1925-2.36150.33721190.25332027X-RAY DIFFRACTION72
2.3615-2.59880.27291500.21712824X-RAY DIFFRACTION100
2.5988-2.97390.28481560.20712445X-RAY DIFFRACTION87
2.9739-3.74350.25041270.20852542X-RAY DIFFRACTION88
3.7435-21.10.241310.17462858X-RAY DIFFRACTION95
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)
15.74142.2945-0.1591.74350.81431.1094-0.3815-0.30820.588-1.24030.22570.3319-0.60540.45090.08570.2614-0.1441-0.03060.24680.03280.447423.92423.6142-15.045
26.0098-1.31690.53914.18360.07840.10550.3861-1.20080.13471.1329-0.4337-0.48290.4613-0.1411-0.09090.4378-0.0963-0.06660.3950.08010.242515.726815.3809-6.0744
31.3198-0.3106-0.11413.2125-2.70652.42980.00890.13050.1662-0.3508-0.3573-0.70080.41030.16410.25920.2076-0.017-0.00790.21710.05630.250818.254717.5815-13.9079
42.5494-2.6725-0.31366.8152-1.05240.5547-0.1931-0.2122-0.01640.93360.20750.6269-0.2163-0.0847-0.03140.167-0.02140.04060.09780.00990.105821.570312.6789-11.435
52.84130.3771.71090.3978-0.3211.89050.2302-0.2442-1.5705-0.09370.5950.0450.57640.1071-0.68560.5010.1894-0.07530.30230.02470.497336.68825.6021-12.0881
63.1188-4.1709-1.3066.22410.493.03550.2378-0.3641.2008-0.17580.0276-1.22860.12450.4754-0.22640.1511-0.01370.02040.17830.00520.240924.56713.5851-23.9386
70.7017-0.0444-0.86023.17760.57731.0902-0.0784-0.27310.04990.04910.1179-0.2193-0.00710.1681-0.05920.1474-0.0439-0.01050.17170.03170.193220.322511.5935-17.5143
81.36180.1602-0.4820.5176-0.56281.13070.3057-0.17660.24330.37680.03410.2741-0.0917-0.1947-0.28250.19050.00730.08390.17780.06090.3021-2.42922.3321-8.7967
91.87230.7891-0.53290.601-0.32950.2814-0.31150.19770.0486-0.24810.25240.14690.2716-0.12410.01630.1639-0.0322-0.03320.20120.06750.13587.4602-3.9969-22.6585
100.4556-0.419-1.74011.83371.01698.93250.04160.44790.0004-0.0888-0.2311-0.58560.0571-0.49630.17050.136-0.0110.05120.1770.03170.182418.6585-5.6623-17.0706
111.6608-0.1710.39712.64340.29040.0727-0.0944-0.08740.1024-0.03580.1417-0.1634-0.064-0.0615-0.04260.137-0.040.01310.11060.05450.144713.29472.6926-15.055
120.7972-0.2522-0.46272.43080.87092.49380.1756-0.134-0.0334-0.12040.1116-0.2503-0.13840.2048-0.22910.1289-0.00780.0020.14510.01660.129215.4817-10.5455-4.8897
137.86251.9857-3.53753.3726-1.99842.24970.48820.35620.49930.72820.19550.2347-0.52080.5383-0.45350.3460.03680.03820.3207-0.06920.073624.3362-14.9443-13.1927
142.1706-1.9266-2.28731.88691.54043.56940.0275-0.41750.02440.08780.3814-0.14440.2850.2697-0.17250.045-0.01860.00960.10790.09950.05884.8354-8.6903-10.4719
151.2916-1.44331.29923.6684-0.48982.99680.1663-0.47530.31210.19050.16150.03370.1785-0.6135-0.33840.20310.0121-0.01130.1870.07020.183411.0796-14.71520.598
161.95891.5070.01511.41960.71824.24720.04820.0912-0.33980.8261-0.0697-0.34661.2568-0.36630.01940.483-0.0989-0.09760.09520.02370.238712.7934-26.2407-7.2293
173.30.6642-0.50762.00341.80072.0269-0.0550.2424-0.05510.6261-0.0379-0.1060.894-0.21720.09240.4268-0.1528-0.05450.16960.04930.177911.6881-24.6775-1.8983
181.43220.85640.67220.65390.57910.45250.3869-0.2639-0.22430.0456-0.28930.14970.204-0.1011-0.07340.1458-0.0471-0.00430.16310.03560.15282.3462-17.1938-14.5642
198.2844-0.8761-5.26352.33091.3794.15730.12960.96-0.4475-0.3464-0.18-0.17920.1181-0.35610.11320.14-0.0347-0.05410.16960.03790.13690.0532-11.8186-25.1289
200.2329-1.1828-0.22146.68711.58370.40730.2995-0.14540.3088-0.0587-0.76831.2664-0.1616-0.41150.22140.1401-0.03690.06180.28040.01860.4544-4.89056.3613-17.832
Refinement TLS group
IDRefine-IDRefine TLS-IDSelection details
1X-RAY DIFFRACTION1(chain A and resid 0:5)
2X-RAY DIFFRACTION2(chain A and resid 6:13)
3X-RAY DIFFRACTION3(chain A and resid 14:28)
4X-RAY DIFFRACTION4(chain A and resid 29:36)
5X-RAY DIFFRACTION5(chain A and resid 40:47)
6X-RAY DIFFRACTION6(chain A and resid 48:60)
7X-RAY DIFFRACTION7(chain A and resid 61:85)
8X-RAY DIFFRACTION8(chain A and resid 86:103)
9X-RAY DIFFRACTION9(chain A and resid 104:121)
10X-RAY DIFFRACTION10(chain A and resid 122:128)
11X-RAY DIFFRACTION11(chain A and resid 129:154)
12X-RAY DIFFRACTION12(chain A and resid 163:176)
13X-RAY DIFFRACTION13(chain A and resid 177:181)
14X-RAY DIFFRACTION14(chain A and resid 182:201)
15X-RAY DIFFRACTION15(chain A and resid 202:216)
16X-RAY DIFFRACTION16(chain A and resid 217:232)
17X-RAY DIFFRACTION17(chain A and resid 233:248)
18X-RAY DIFFRACTION18(chain A and resid 249:277)
19X-RAY DIFFRACTION19(chain A and resid 278:287)
20X-RAY DIFFRACTION20(chain A and resid 288:298)

+
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://pdbjlc1.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