[English] 日本語
Yorodumi
- PDB-6p8f: Crystal structure of CDK4 in complex with CyclinD1 and P27 -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 6p8f
TitleCrystal structure of CDK4 in complex with CyclinD1 and P27
Components
  • Cyclin-dependent kinase 4
  • Cyclin-dependent kinase inhibitor 1B
  • G1/S-specific cyclin-D1
Keywordscell cycle / transferase / Cyclin-dependent kinase / kinase inhibitor
Function / homology
Function and homology information


cyclin-dependent protein kinase regulator activity / cyclin D1-CDK4 complex / cyclin D2-CDK4 complex / Evasion of Oncogene Induced Senescence Due to Defective p16INK4A binding to CDK4 / Evasion of Oxidative Stress Induced Senescence Due to Defective p16INK4A binding to CDK4 / negative regulation of cardiac muscle tissue regeneration / Evasion of Oncogene Induced Senescence Due to Defective p16INK4A binding to CDK4 and CDK6 / Evasion of Oxidative Stress Induced Senescence Due to Defective p16INK4A binding to CDK4 and CDK6 / Drug-mediated inhibition of CDK4/CDK6 activity / regulation of transcription initiation by RNA polymerase II ...cyclin-dependent protein kinase regulator activity / cyclin D1-CDK4 complex / cyclin D2-CDK4 complex / Evasion of Oncogene Induced Senescence Due to Defective p16INK4A binding to CDK4 / Evasion of Oxidative Stress Induced Senescence Due to Defective p16INK4A binding to CDK4 / negative regulation of cardiac muscle tissue regeneration / Evasion of Oncogene Induced Senescence Due to Defective p16INK4A binding to CDK4 and CDK6 / Evasion of Oxidative Stress Induced Senescence Due to Defective p16INK4A binding to CDK4 and CDK6 / Drug-mediated inhibition of CDK4/CDK6 activity / regulation of transcription initiation by RNA polymerase II / autophagic cell death / Leydig cell differentiation / RUNX3 regulates WNT signaling / FOXO-mediated transcription of cell cycle genes / response to leptin / regulation of cell cycle G1/S phase transition / Transcriptional regulation by RUNX2 / cellular response to lithium ion / negative regulation of mitotic cell cycle / cyclin-dependent protein serine/threonine kinase inhibitor activity / proline-rich region binding / regulation of cyclin-dependent protein serine/threonine kinase activity / nuclear export / RHO GTPases activate CIT / cyclin-dependent protein serine/threonine kinase activator activity / AKT phosphorylates targets in the cytosol / Regulation of RUNX1 Expression and Activity / response to iron ion / ubiquitin ligase activator activity / cyclin-dependent protein serine/threonine kinase regulator activity / response to UV-A / molecular function inhibitor activity / response to vitamin E / response to corticosterone / p53-Dependent G1 DNA Damage Response / PTK6 Regulates Cell Cycle / Constitutive Signaling by AKT1 E17K in Cancer / Cul4A-RING E3 ubiquitin ligase complex / Defective binding of RB1 mutants to E2F1,(E2F2, E2F3) / protein kinase inhibitor activity / animal organ regeneration / microtubule organizing center / Transcriptional Regulation by VENTX / negative regulation of vascular associated smooth muscle cell proliferation / RUNX3 regulates p14-ARF / bicellular tight junction / response to magnesium ion / Estrogen-dependent nuclear events downstream of ESR-membrane signaling / response to X-ray / positive regulation of G2/M 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 / positive regulation of G1/S transition of mitotic cell cycle / Regulation of MITF-M-dependent genes involved in cell cycle and proliferation / Cyclin E associated events during G1/S transition / cyclin-dependent protein kinase holoenzyme complex / Cyclin A:Cdk2-associated events at S phase entry / SPOP-mediated proteasomal degradation of PD-L1(CD274) / transcription repressor complex / regulation of G1/S transition of mitotic cell cycle / mitotic G1 DNA damage checkpoint signaling / FLT3 Signaling / liver development / cyclin binding / positive regulation of DNA replication / DNA damage response, signal transduction by p53 class mediator / protein serine/threonine kinase activator activity / G1/S transition of mitotic cell cycle / Ubiquitin-dependent degradation of Cyclin D / response to calcium ion / negative regulation of cell growth / Transcriptional regulation of white adipocyte differentiation / negative regulation of epithelial cell proliferation / Oncogene Induced Senescence / response to estrogen / DNA Damage/Telomere Stress Induced Senescence / cellular senescence / positive regulation of fibroblast proliferation / G2/M transition of mitotic cell cycle / Meiotic recombination / Pre-NOTCH Transcription and Translation / histone deacetylase binding / Transcriptional regulation of granulopoiesis / SCF(Skp2)-mediated degradation of p27/p21 / RMTs methylate histone arginines / positive regulation of protein catabolic process / heart development / Cyclin D associated events in G1 / transcription corepressor activity / response to estradiol / regulation of gene expression / protein-folding chaperone binding / nuclear membrane / Interleukin-4 and Interleukin-13 signaling / Senescence-Associated Secretory Phenotype (SASP) / transcription regulator complex / protein phosphatase binding / cellular response to hypoxia / Oxidative Stress Induced Senescence
Similarity search - Function
Cyclin-dependent kinase inhibitor domain / Cyclin-dependent kinase inhibitor domain superfamily / Cyclin-dependent kinase inhibitor / Cyclin, C-terminal domain / : / Cyclins signature. / Cyclin / Cyclin-like / Cyclin, C-terminal domain / Cyclin_C ...Cyclin-dependent kinase inhibitor domain / Cyclin-dependent kinase inhibitor domain superfamily / Cyclin-dependent kinase inhibitor / Cyclin, C-terminal domain / : / Cyclins signature. / Cyclin / Cyclin-like / Cyclin, C-terminal domain / Cyclin_C / 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
Cyclin-dependent kinase 4 / G1/S-specific cyclin-D1 / Cyclin-dependent kinase inhibitor 1B
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.89 Å
AuthorsGuiley, K.Z. / Stevenson, J.W. / Lou, K. / Barkovich, K.J. / Bunch, K. / Tripathi, S.M. / Shokat, K.M. / Rubin, S.M.
Funding support United States, 2items
OrganizationGrant numberCountry
National Institutes of Health/National Cancer Institute (NIH/NCI)GM124148 United States
National Institutes of Health/National Cancer Institute (NIH/NCI)CA206244 United States
CitationJournal: Science / Year: 2019
Title: p27 allosterically activates cyclin-dependent kinase 4 and antagonizes palbociclib inhibition.
Authors: Guiley, K.Z. / Stevenson, J.W. / Lou, K. / Barkovich, K.J. / Kumarasamy, V. / Wijeratne, T.U. / Bunch, K.L. / Tripathi, S. / Knudsen, E.S. / Witkiewicz, A.K. / Shokat, K.M. / Rubin, S.M.
History
DepositionJun 7, 2019Deposition site: RCSB / Processing site: RCSB
Revision 1.0Dec 25, 2019Provider: repository / Type: Initial release
Revision 1.1Oct 30, 2024Group: Data collection / Database references / Structure summary
Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / database_2 / pdbx_entry_details / pdbx_modification_feature
Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession / _pdbx_entry_details.has_protein_modification

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: G1/S-specific cyclin-D1
B: Cyclin-dependent kinase 4
C: Cyclin-dependent kinase inhibitor 1B


Theoretical massNumber of molelcules
Total (without water)72,1903
Polymers72,1903
Non-polymers00
Water00
1


  • Idetical with deposited unit
  • defined by author&software
  • Evidence: gel filtration
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area6280 Å2
ΔGint-43 kcal/mol
Surface area27050 Å2
MethodPISA
Unit cell
Length a, b, c (Å)62.855, 66.628, 184.240
Angle α, β, γ (deg.)90.00, 90.00, 90.00
Int Tables number18
Space group name H-MP21221

-
Components

#1: Protein G1/S-specific cyclin-D1 / B-cell lymphoma 1 protein / BCL-1 / BCL-1 oncogene / PRAD1 oncogene


Mass: 28445.293 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: CCND1, BCL1, PRAD1 / Production host: Spodoptera frugiperda (fall armyworm) / References: UniProt: P24385
#2: Protein Cyclin-dependent kinase 4 / Cell division protein kinase 4 / PSK-J3


Mass: 33947.930 Da / Num. of mol.: 1 / Mutation: G48E, G49E
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: CDK4 / Production host: Spodoptera frugiperda (fall armyworm) / References: UniProt: P11802, cyclin-dependent kinase
#3: Protein Cyclin-dependent kinase inhibitor 1B / Cyclin-dependent kinase inhibitor p27 / p27Kip1


Mass: 9796.787 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: CDKN1B, KIP1 / Production host: Spodoptera frugiperda (fall armyworm) / References: UniProt: P46527
Has ligand of interestY
Has protein modificationY

-
Experimental details

-
Experiment

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

-
Sample preparation

CrystalDensity Matthews: 2.67 Å3/Da / Density % sol: 58.97 %
Crystal growTemperature: 295 K / Method: vapor diffusion, sitting drop / pH: 7
Details: 100mM Tris (7.0) 17% PEG 3350 100 mM CaCl2 10 mM MgCl2

-
Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: APS / Beamline: 23-ID-D / Wavelength: 1 Å
DetectorType: DECTRIS PILATUS 6M / Detector: PIXEL / Date: Feb 8, 2018
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1 Å / Relative weight: 1
ReflectionResolution: 2.89→46.06 Å / Num. obs: 18044 / % possible obs: 99.8 % / Redundancy: 12.9 % / Rmerge(I) obs: 0.18 / Rpim(I) all: 0.056 / Net I/σ(I): 14.3
Reflection shellResolution: 2.89→3.07 Å / Redundancy: 12.8 % / Rmerge(I) obs: 0.99 / Mean I/σ(I) obs: 2.9 / Num. unique obs: 2830 / CC1/2: 0.81 / Rpim(I) all: 0.296

-
Processing

Software
NameVersionClassification
PHENIX(1.13_2998: ???)refinement
XDSdata reduction
Aimlessdata scaling
PHASERphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT / Resolution: 2.89→46.06 Å / SU ML: 0.31 / Cross valid method: FREE R-VALUE / σ(F): 0 / Phase error: 24.02
RfactorNum. reflection% reflection
Rfree0.2422 848 4.88 %
Rwork0.1862 --
obs0.189 17381 96.38 %
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å
Refinement stepCycle: LAST / Resolution: 2.89→46.06 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms4498 0 0 0 4498
Refine LS restraints
Refine-IDTypeDev idealNumber
X-RAY DIFFRACTIONf_bond_d0.0044597
X-RAY DIFFRACTIONf_angle_d0.6556223
X-RAY DIFFRACTIONf_dihedral_angle_d6.4772832
X-RAY DIFFRACTIONf_chiral_restr0.04694
X-RAY DIFFRACTIONf_plane_restr0.005805
LS refinement shell
Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkRefine-ID% reflection obs (%)
2.89-3.0710.31191320.23012516X-RAY DIFFRACTION90
3.071-3.30810.28491130.25112679X-RAY DIFFRACTION95
3.3081-3.64080.26521400.20332716X-RAY DIFFRACTION97
3.6408-4.16740.2631550.1762790X-RAY DIFFRACTION98
4.1674-5.24930.20711490.15292845X-RAY DIFFRACTION99
5.2493-46.06580.2141590.17822987X-RAY DIFFRACTION99
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)
10.15950.791-0.27525.84912.67898.42490.8512-0.199-1.85050.58311.2939-0.59181.2617-0.4584-1.2560.8266-0.0527-0.19240.49140.1321.14859.0577-37.646-24.0655
27.51144.45764.19865.03311.48547.60921.4313-0.5065-1.25350.40930.1033-0.50263.0668-0.4165-1.11221.0669-0.0375-0.49010.72970.17861.38612.3166-38.5002-19.0601
39.24596.06683.97874.41951.32199.43130.8859-0.65750.00690.5747-1.1319-1.32420.16770.61410.14160.2827-0.0366-0.08920.48480.05090.520916.33-5.5117-39.5542
45.5724-1.67450.05714.80160.59864.54260.10650.13190.1922-0.37360.0546-0.29780.06230.3138-0.12270.2174-0.05750.01930.14950.02270.2469-3.5944-21.1318-49.3378
53.81870.12970.16372.57981.94662.9564-0.025-0.0238-0.46480.22730.08190.27810.2531-0.1351-0.02260.22070.0162-0.00380.14860.05290.3697-7.9847-24.7051-39.9566
64.27881.2517-1.18312.11970.31520.6865-0.0499-0.20160.42120.59520.2902-0.1051-0.08970.1329-0.25440.2361-0.0377-0.00590.2728-0.02470.29185.92180.9912-44.5661
74.93513.48312.29199.28436.22957.8487-0.1336-0.13320.36920.62650.03370.4869-0.0551-0.38540.24250.23340.00460.07070.28390.04620.2706-2.7536-0.849-50.1293
85.036-0.42850.37717.15381.59140.35580.00240.61440.0206-0.7149-0.0077-0.06550.2146-0.35210.00940.3668-0.0470.0320.35860.00120.15994.0615-7.3775-55.3567
91.2271-0.12510.28110.0067-0.0570.0945-0.6650.51230.8733-1.5233-0.58541.684-0.6798-0.54830.11980.75020.2245-0.56750.2510.32750.96122.850111.2977-57.5672
108.4477-5.25083.37218.8308-5.28369.96540.26830.1875-0.9842-0.57820.1229-0.4312-0.02810.9103-0.40610.2768-0.0288-0.01080.298-0.0550.386415.28660.674-53.8556
114.14432.87264.18616.03021.80338.10240.03821.9263-1.2504-0.54960.4668-0.09240.40810.5091-0.32880.4782-0.03820.01690.4035-0.03760.30880.0185-7.8554-62.816
124.1514-2.80144.89875.1925-1.77315.8722-0.0885-0.558-0.8750.9020.1638-0.5159-0.0529-0.0764-0.19580.5503-0.0447-0.07540.44950.03390.53976.6028-25.8064-24.3192
134.10411.76531.15343.79331.04442.35580.3486-0.3096-0.51810.7208-0.0524-0.15580.59840.0119-0.32870.52190.0076-0.06730.38210.03910.291618.6554-16.443-18.9294
141.13650.5722-1.67355.48473.51596.21620.43320.06010.37250.7691-0.95951.5360.4721-1.1582-0.25270.5371-0.07630.17470.89660.09780.33148.3174-6.5264-13.098
156.4875-0.8887-0.30153.24813.01385.53460.4161-1.3044-0.05581.0641-0.06830.5219-0.47860.0577-0.21480.82370.01040.19630.58940.06460.327916.4888-1.5167-5.9611
165.95740.01583.7824.4213-1.61333.91630.27650.04582.0909-0.7225-0.3330.8668-0.6895-0.6946-0.07611.11980.3030.3090.8745-0.01390.7313.794911.7439-9.823
178.3-2.8406-4.23094.87633.86637.63340.5553-0.54040.86021.00730.2495-0.1552-0.98590.4056-0.7190.8415-0.08250.18520.39730.00720.47619.76696.8943-9.5219
180.54881.46-0.62335.521.74017.86880.31880.27970.1829-0.66310.3069-0.7674-0.05590.6555-0.32980.45520.04140.10840.51420.09250.296829.7767-0.3121-23.3829
192.22672.4632-1.27613.3588-2.88814.31040.13510.0277-0.56920.40.23391.4039-0.0548-0.7077-0.10680.2653-0.0373-0.06690.5012-0.07320.8392-19.7781-25.8238-49.9524
204.185-1.12194.16340.2949-1.22644.41641.0145-0.0112-2.0481.294-0.0797-0.44991.42120.0191-0.9020.86380.1419-0.30380.4378-0.13181.0025-2.4808-39.7297-36.103
Refinement TLS group
IDRefine-IDRefine TLS-IDSelection detailsAuth asym-IDAuth seq-ID
1X-RAY DIFFRACTION1( CHAIN C AND RESID 60:64 )C60 - 64
2X-RAY DIFFRACTION2( CHAIN C AND RESID 65:79 )C65 - 79
3X-RAY DIFFRACTION3( CHAIN A AND RESID 21:36 )A21 - 36
4X-RAY DIFFRACTION4( CHAIN A AND RESID 37:89 )A37 - 89
5X-RAY DIFFRACTION5( CHAIN A AND RESID 90:156 )A90 - 156
6X-RAY DIFFRACTION6( CHAIN A AND RESID 157:171 )A157 - 171
7X-RAY DIFFRACTION7( CHAIN A AND RESID 172:191 )A172 - 191
8X-RAY DIFFRACTION8( CHAIN A AND RESID 192:216 )A192 - 216
9X-RAY DIFFRACTION9( CHAIN A AND RESID 217:225 )A217 - 225
10X-RAY DIFFRACTION10( CHAIN A AND RESID 226:240 )A226 - 240
11X-RAY DIFFRACTION11( CHAIN A AND RESID 241:264 )A241 - 264
12X-RAY DIFFRACTION12( CHAIN B AND RESID 18:62 )B18 - 62
13X-RAY DIFFRACTION13( CHAIN B AND RESID 63:151 )B63 - 151
14X-RAY DIFFRACTION14( CHAIN B AND RESID 152:190 )B152 - 190
15X-RAY DIFFRACTION15( CHAIN B AND RESID 191:227 )B191 - 227
16X-RAY DIFFRACTION16( CHAIN B AND RESID 228:242 )B228 - 242
17X-RAY DIFFRACTION17( CHAIN B AND RESID 243:282 )B243 - 282
18X-RAY DIFFRACTION18( CHAIN B AND RESID 283:296 )B283 - 296
19X-RAY DIFFRACTION19( CHAIN C AND RESID 24:37 )C24 - 37
20X-RAY DIFFRACTION20( CHAIN C AND RESID 38:59 )C38 - 59

+
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