[English] 日本語
Yorodumi
- PDB-9csk: Crystal structure of CDK4 cyclin D1 in complex with atirmociclib -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 9csk
TitleCrystal structure of CDK4 cyclin D1 in complex with atirmociclib
Components
  • Cyclin-dependent kinase 4
  • G1/S-specific cyclin-D1
KeywordsTransferase/Inhibitor/Cell Cycle / Kinase / Inhibitor / Cancer / Transferase-Inhibitor-Cell Cycle complex
Function / homology
Function and homology information


cyclin D3-CDK4 complex / 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 / re-entry into mitotic cell cycle / cyclin D1-CDK6 complex / cellular response to ionomycin / regulation of transcription initiation by RNA polymerase II / Evasion of Oncogene Induced Senescence Due to Defective p16INK4A binding to CDK4 and CDK6 ...cyclin D3-CDK4 complex / 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 / re-entry into mitotic cell cycle / cyclin D1-CDK6 complex / cellular response to ionomycin / regulation of transcription initiation by RNA polymerase II / 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 type B pancreatic cell proliferation / RUNX3 regulates WNT signaling / response to leptin / positive regulation of mammary gland epithelial cell proliferation / Transcriptional regulation by RUNX2 / cellular response to phorbol 13-acetate 12-myristate / positive regulation of cyclin-dependent protein serine/threonine kinase activity / cyclin-dependent protein serine/threonine kinase activator activity / proline-rich region binding / Regulation of RUNX1 Expression and Activity / cyclin-dependent protein serine/threonine kinase regulator activity / mammary gland epithelial cell proliferation / response to UV-A / negative regulation of epithelial cell differentiation / PTK6 Regulates Cell Cycle / fat cell differentiation / Defective binding of RB1 mutants to E2F1,(E2F2, E2F3) / microtubule organizing center / Transcriptional Regulation by VENTX / RUNX3 regulates p14-ARF / mammary gland alveolus development / Estrogen-dependent nuclear events downstream of ESR-membrane signaling / bicellular tight junction / positive regulation of G1/S transition of mitotic cell cycle / cyclin-dependent kinase / cyclin-dependent protein serine/threonine kinase activity / Regulation of MITF-M-dependent genes involved in cell cycle and proliferation / endoplasmic reticulum unfolded protein response / cyclin-dependent protein kinase holoenzyme complex / regulation of G2/M transition of mitotic cell cycle / mitotic G1 DNA damage checkpoint signaling / positive regulation of G2/M transition of mitotic cell cycle / lactation / transcription repressor complex / cellular response to interleukin-4 / cyclin binding / liver regeneration / Ubiquitin-dependent degradation of Cyclin D / Oncogene Induced Senescence / Meiotic recombination / Transcriptional regulation of white adipocyte differentiation / Pre-NOTCH Transcription and Translation / SCF(Skp2)-mediated degradation of p27/p21 / Wnt signaling pathway / RMTs methylate histone arginines / G1/S transition of mitotic cell cycle / histone deacetylase binding / Transcriptional regulation of granulopoiesis / positive regulation of fibroblast proliferation / neuron differentiation / transcription corepressor activity / Cyclin D associated events in G1 / positive regulation of protein phosphorylation / regulation of gene expression / cellular response to lipopolysaccharide / Senescence-Associated Secretory Phenotype (SASP) / Interleukin-4 and Interleukin-13 signaling / Oxidative Stress Induced Senescence / nuclear membrane / transcription regulator complex / Estrogen-dependent gene expression / negative regulation of neuron apoptotic process / protein kinase activity / regulation of cell cycle / protein phosphorylation / response to xenobiotic stimulus / cell division / protein serine kinase activity / positive regulation of cell population proliferation / DNA damage response / protein kinase binding / chromatin / nucleolus / enzyme binding / negative regulation of transcription by RNA polymerase II / signal transduction / nucleoplasm / ATP binding / nucleus / cytosol / cytoplasm
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 / : / 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
Similarity search - Domain/homology
: / Cyclin-dependent kinase 4 / G1/S-specific cyclin-D1
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.253 Å
AuthorsJohnson, E.
Funding support United States, 1items
OrganizationGrant numberCountry
Not funded United States
CitationJournal: Cancer Cell / Year: 2025
Title: CDK4 selective inhibition improves preclinical anti-tumor efficacy and safety.
Authors: Palmer, C.L. / Boras, B. / Pascual, B. / Li, N. / Li, D. / Garza, S. / Huser, N. / Yuan, J.T. / Cianfrogna, J.A. / Sung, T. / McMillan, E. / Wei, N. / Carmody, J. / Kang, A.N. / Darensburg, ...Authors: Palmer, C.L. / Boras, B. / Pascual, B. / Li, N. / Li, D. / Garza, S. / Huser, N. / Yuan, J.T. / Cianfrogna, J.A. / Sung, T. / McMillan, E. / Wei, N. / Carmody, J. / Kang, A.N. / Darensburg, S. / Dodd, T. / Oakley, J.V. / Solowiej, J. / Nguyen, L. / Orr, S.T.M. / Chen, P. / Johnson, E. / Yu, X. / Diehl, W.C. / Gallego, G.M. / Jalaie, M. / Ferre, R.A. / Cho-Schultz, S. / Shen, H. / Deal, J.G. / Zhang, Q. / Baffi, T.R. / Xu, M. / Roh, W. / Lapira-Miller, J. / Goudeau, J. / Yu, Y. / Gupta, R. / Kim, K. / Dann, S.G. / Kan, Z. / Kath, J.C. / Nair, S.K. / Miller, N. / Murray, B.W. / Nager, A.R. / Quinlan, C. / Petroski, M.D. / Zhang, C. / Sacaan, A. / VanArsdale, T. / Anders, L.
History
DepositionJul 24, 2024Deposition site: RCSB / Processing site: RCSB
Revision 1.0Mar 26, 2025Provider: repository / Type: Initial release

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: G1/S-specific cyclin-D1
B: Cyclin-dependent kinase 4
C: G1/S-specific cyclin-D1
D: Cyclin-dependent kinase 4
hetero molecules


Theoretical massNumber of molelcules
Total (without water)130,5606
Polymers129,6324
Non-polymers9282
Water5,909328
1
A: G1/S-specific cyclin-D1
B: Cyclin-dependent kinase 4
hetero molecules


Theoretical massNumber of molelcules
Total (without water)65,2803
Polymers64,8162
Non-polymers4641
Water362
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area2000 Å2
ΔGint-12 kcal/mol
Surface area24190 Å2
MethodPISA
2
C: G1/S-specific cyclin-D1
D: Cyclin-dependent kinase 4
hetero molecules


Theoretical massNumber of molelcules
Total (without water)65,2803
Polymers64,8162
Non-polymers4641
Water362
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area2500 Å2
ΔGint-14 kcal/mol
Surface area24690 Å2
MethodPISA
Unit cell
Length a, b, c (Å)56.511, 64.289, 186.208
Angle α, β, γ (deg.)90.00, 91.67, 90.00
Int Tables number4
Space group name H-MP1211

-
Components

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


Mass: 29276.309 Da / Num. of mol.: 2
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: 35539.707 Da / Num. of mol.: 2 / Mutation: DELTA(43-47)EE
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: Chemical ChemComp-A1AZ4 / Atirmociclib


Mass: 463.933 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C22H27ClFN5O3 / Feature type: SUBJECT OF INVESTIGATION
#4: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 328 / Source method: isolated from a natural source / Formula: H2O
Has ligand of interestY
Has protein modificationN

-
Experimental details

-
Experiment

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

-
Sample preparation

CrystalDensity Matthews: 2.87 Å3/Da / Density % sol: 57.18 %
Crystal growTemperature: 294.15 K / Method: vapor diffusion, sitting drop
Details: Salt: 0.1 M DL-Malic acid Polymer: 12.4642857143 %w/v PEG 3350 Buffer: 0.1 M HEPES (pH 6.91) Additive: 10mM DTT [protein] 6mg/ml

-
Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: APS / Beamline: 17-ID / Wavelength: 1 Å
DetectorType: DECTRIS EIGER2 XE 16M / Detector: PIXEL / Date: Mar 16, 2021
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1 Å / Relative weight: 1
ReflectionResolution: 2.201→186.129 Å / Num. obs: 49529 / % possible obs: 91 % / Redundancy: 3.4 % / CC1/2: 0.997 / Net I/σ(I): 7.7
Reflection shellResolution: 2.201→2.414 Å / Num. unique obs: 2477 / CC1/2: 0.587 / % possible all: 54.6

-
Processing

Software
NameVersionClassification
BUSTER2.11.8 (24-FEB-2021)refinement
XDSdata reduction
STARANISOdata scaling
PHASERphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT / Resolution: 2.253→38.93 Å / Cor.coef. Fo:Fc: 0.928 / Cor.coef. Fo:Fc free: 0.894 / SU R Cruickshank DPI: 0.417 / Cross valid method: THROUGHOUT / σ(F): 0 / SU R Blow DPI: 0.415 / SU Rfree Blow DPI: 0.272 / SU Rfree Cruickshank DPI: 0.276
RfactorNum. reflection% reflectionSelection details
Rfree0.2701 2479 5.01 %RANDOM
Rwork0.2239 ---
obs0.2262 49482 77.9 %-
Displacement parametersBiso mean: 59.01 Å2
Baniso -1Baniso -2Baniso -3
1--4.2145 Å20 Å2-0.4899 Å2
2---0.5915 Å20 Å2
3---4.8061 Å2
Refine analyzeLuzzati coordinate error obs: 0.34 Å
Refinement stepCycle: LAST / Resolution: 2.253→38.93 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms8232 0 70 350 8652
Refine LS restraints
Refine-IDTypeDev idealNumberRestraint functionWeight
X-RAY DIFFRACTIONt_bond_d0.0088492HARMONIC2
X-RAY DIFFRACTIONt_angle_deg0.9811521HARMONIC2
X-RAY DIFFRACTIONt_dihedral_angle_d2961SINUSOIDAL2
X-RAY DIFFRACTIONt_incorr_chiral_ct
X-RAY DIFFRACTIONt_pseud_angle
X-RAY DIFFRACTIONt_trig_c_planes
X-RAY DIFFRACTIONt_gen_planes1417HARMONIC5
X-RAY DIFFRACTIONt_it8492HARMONIC10
X-RAY DIFFRACTIONt_nbd
X-RAY DIFFRACTIONt_omega_torsion2.8
X-RAY DIFFRACTIONt_other_torsion20.35
X-RAY DIFFRACTIONt_improper_torsion
X-RAY DIFFRACTIONt_chiral_improper_torsion1086SEMIHARMONIC5
X-RAY DIFFRACTIONt_sum_occupancies
X-RAY DIFFRACTIONt_utility_distance
X-RAY DIFFRACTIONt_utility_angle
X-RAY DIFFRACTIONt_utility_torsion
X-RAY DIFFRACTIONt_ideal_dist_contact7116SEMIHARMONIC4
LS refinement shellResolution: 2.253→2.35 Å
RfactorNum. reflection% reflection
Rfree0.3317 -5.86 %
Rwork0.2822 932 -
obs--13.22 %
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)
11.6043-0.61790.8021.1313-0.21641.00280.03340.02040.0297-0.0817-0.00910.0106-0.08050.0069-0.02430.0182-0.00030.04070.02920.00550.164313.470110.1561.6595
22.52720.1757-1.50720.3277-0.3892.8509-0.0419-0.1224-0.1761-0.01710.13290.03080.1722-0.3387-0.0910.01390.0079-0.0390.37780.13260.1103-1.9949-4.00632.6151
31.50810.7956-0.79051.6166-0.53630.98220.0741-0.01730.00690.0823-0.04640.05330.0399-0.0111-0.02780.0218-0.0048-0.0278-0.00390.00020.145939.2712-24.15191.5876
42.9953-0.6571.23070.4218-0.60851.45530.03790.3048-0.0517-0.0716-0.00260.0083-0.0313-0.1191-0.03530.05830.01170.00230.25840.04020.070523.0941-11.87960.3432
Refinement TLS group
IDRefine-IDRefine TLS-IDSelection details
1X-RAY DIFFRACTION1{ A|25 - A|257 }
2X-RAY DIFFRACTION2{ B|4 - B|295 }
3X-RAY DIFFRACTION3{ C|25 - C|258 }
4X-RAY DIFFRACTION4{ D|4 - D|295 }

+
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