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- PDB-13gk: CDK2 in complex with INCB125496 -

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Basic information

Entry
Database: PDB / ID: 13gk
TitleCDK2 in complex with INCB125496
ComponentsCyclin-dependent kinase 2
KeywordsTRANSFERASE / CDK2 / serine/threonine kinase / cell cycle regulation / aminopyrimidine / inhibitor / 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 / G2 Phase / Y chromosome / cyclin-dependent protein kinase activity / regulation of heterochromatin organization / 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 / G2 Phase / Y chromosome / cyclin-dependent protein kinase activity / regulation of heterochromatin organization / 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 / telomere maintenance in response to DNA damage / Regulation of APC/C activators between G1/S and early anaphase / G0 and Early G1 / Activation of the pre-replicative complex / Telomere Extension By Telomerase / cyclin-dependent kinase / cyclin-dependent protein serine/threonine kinase activity / TP53 Regulates Transcription of Genes Involved in G1 Cell Cycle Arrest / Regulation of MITF-M-dependent genes involved in cell cycle and proliferation / Cajal body / Activation of ATR in response to replication stress / Cyclin E associated events during G1/S transition / centrosome duplication / Cyclin A:Cdk2-associated events at S phase entry / Cyclin A/B1/B2 associated events during G2/M transition / cyclin-dependent protein kinase holoenzyme complex / condensed chromosome / mitotic G1 DNA damage checkpoint signaling / cellular response to nitric oxide / post-translational protein modification / positive regulation of DNA replication / cyclin binding / negative regulation of protein localization to chromatin / regulation of mitotic cell cycle / meiotic cell cycle / G1/S transition of mitotic cell cycle / G2/M transition of mitotic cell cycle / peptidyl-serine phosphorylation / cellular senescence / DNA Damage/Telomere Stress Induced Senescence / Meiotic recombination / CDK-mediated phosphorylation and removal of Cdc6 / Transcriptional regulation of granulopoiesis / SCF(Skp2)-mediated degradation of p27/p21 / Orc1 removal from chromatin / Cyclin D associated events in G1 / Regulation of TP53 Degradation / nuclear envelope / Factors involved in megakaryocyte development and platelet production / transcription regulator complex / ciliary basal body / Processing of DNA double-strand break ends / Senescence-Associated Secretory Phenotype (SASP) / Regulation of TP53 Activity through Phosphorylation / DNA replication / cell division / Ras protein signal transduction / protein phosphorylation / chromosome, telomeric region / endosome / chromatin remodeling / protein domain specific binding / DNA repair / protein serine kinase activity / protein serine/threonine kinase activity / centrosome / positive regulation of cell population proliferation / magnesium ion binding / signal transduction / nucleoplasm / ATP binding / nucleus / cytosol / cytoplasm
Similarity search - Function
: / 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
: / DI(HYDROXYETHYL)ETHER / Cyclin-dependent kinase 2
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 1.44 Å
AuthorsEpling, L.B. / Fenalti, F.
Funding support United States, 1items
OrganizationGrant numberCountry
Other private United States
CitationJournal: J.Med.Chem. / Year: 2026
Title: Discovery of INCB127443: A Potent and Orally Available Inhibitor of Cyclin-Dependent Kinase 2
Authors: Mukai, K. / Smith, B.R. / Ye, Q. / Epling, L.B. / Lai, C. / Huo, L. / Bowen, S. / Drake, K. / Kennedy, K. / Boer, J. / Zimmer, D. / Zhang, W. / Hansbury, M.J. / Chand, S. / Li, J. / Zhang, G. ...Authors: Mukai, K. / Smith, B.R. / Ye, Q. / Epling, L.B. / Lai, C. / Huo, L. / Bowen, S. / Drake, K. / Kennedy, K. / Boer, J. / Zimmer, D. / Zhang, W. / Hansbury, M.J. / Chand, S. / Li, J. / Zhang, G. / Stump, K. / Lo, Y. / Favata, M. / Yang, G. / Covington, M. / Deller, M.C. / Macarron, R. / Jackson, J. / Mayes, P. / Kim, S. / Wang, X. / Hummel, J.R. / Yao, W.
History
DepositionMay 5, 2026Deposition site: RCSB / Processing site: RCSB
Revision 1.0Sep 30, 2026Provider: repository / Type: Initial release

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Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

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Assembly

Deposited unit
A: Cyclin-dependent kinase 2
hetero molecules


Theoretical massNumber of molelcules
Total (without water)34,8515
Polymers33,9761
Non-polymers8744
Water2,522140
1


  • Idetical with deposited unit
  • defined by author
  • Evidence: fluorescence resonance energy transfer
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Unit cell
Length a, b, c (Å)53.659, 71.935, 72.282
Angle α, β, γ (deg.)90.000, 90.000, 90.000
Int Tables number19
Space group name H-MP212121
Space group name HallP2ac2ab
Symmetry operation#1: x,y,z
#2: x+1/2,-y+1/2,-z
#3: -x,y+1/2,-z+1/2
#4: -x+1/2,-y,z+1/2

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Components

#1: Protein Cyclin-dependent kinase 2 / Cell division protein kinase 2 / p33 protein kinase


Mass: 33976.488 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Details: chain breaks due to lack of electron density / Source: (gene. exp.) Homo sapiens (human) / Gene: CDK2, CDKN2 / Production host: Escherichia coli BL21(DE3) (bacteria) / Variant (production host): R3 / References: UniProt: P24941, cyclin-dependent kinase
#2: Chemical ChemComp-GOL / GLYCEROL / GLYCERIN / PROPANE-1,2,3-TRIOL


Mass: 92.094 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C3H8O3
#3: Chemical ChemComp-A1DFY / 4-[(1M)-1-{4-[(azetidin-1-yl)methyl]-2-chlorophenyl}-1H-imidazol-4-yl]-N-[1-(methanesulfonyl)piperidin-4-yl]-5-(trifluoromethyl)pyrimidin-2-amine


Mass: 570.030 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C24H27ClF3N7O2S / Feature type: SUBJECT OF INVESTIGATION
#4: Chemical ChemComp-PEG / DI(HYDROXYETHYL)ETHER


Mass: 106.120 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C4H10O3
#5: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 140 / Source method: isolated from a natural source / Formula: H2O
Has ligand of interestY
Has protein modificationN

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Experimental details

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Experiment

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

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Sample preparation

CrystalDensity Matthews: 2.06 Å3/Da / Density meas: 40.2 Mg/m3 / Density % sol: 40.09 %
Crystal growTemperature: 293 K / Method: vapor diffusion, sitting drop
Details: 0.1 M Tris pH 8.5, 0.2 M trimethylamine N-oxide, 20% PEG 2000 MME

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Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: MAX IV / Beamline: BioMAX / Wavelength: 0.9763 Å
DetectorType: DECTRIS EIGER X 16M / Detector: PIXEL / Date: Jul 8, 2021
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.9763 Å / Relative weight: 1
ReflectionResolution: 1.44→43.08 Å / Num. obs: 50713 / % possible obs: 98.48 % / Redundancy: 13.1 % / Biso Wilson estimate: 21.92 Å2 / CC1/2: 1 / CC star: 1 / Rmerge(I) obs: 0.067 / Rpim(I) all: 0.019 / Rrim(I) all: 0.07 / Net I/σ(I): 15.29
Reflection shellResolution: 1.44→1.48 Å / Mean I/σ(I) obs: 0.93 / Num. unique obs: 3378 / CC1/2: 0.514 / CC star: 0.824 / Rrim(I) all: 2.2 / % possible all: 90.02

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Processing

Software
NameVersionClassification
PHENIX1.21.2_5419refinement
XDSdata reduction
STARANISOdata scaling
DIMPLEphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT / Resolution: 1.44→43.08 Å / SU ML: 0.2219 / Cross valid method: FREE R-VALUE / σ(F): 1.33 / Phase error: 27.1718
Stereochemistry target values: GeoStd + Monomer Library + CDL v1.2
RfactorNum. reflection% reflectionSelection details
Rfree0.2095 1990 3.94 %RANDOM
Rwork0.1867 48564 --
obs0.1876 50553 98.48 %-
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.1 Å / Solvent model: FLAT BULK SOLVENT MODEL
Displacement parametersBiso mean: 34.13 Å2
Refinement stepCycle: LAST / Resolution: 1.44→43.08 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms2283 0 58 140 2481
Refine LS restraints
Refine-IDTypeDev idealNumber
X-RAY DIFFRACTIONf_bond_d0.01212502
X-RAY DIFFRACTIONf_angle_d1.25133410
X-RAY DIFFRACTIONf_chiral_restr0.0987369
X-RAY DIFFRACTIONf_plane_restr0.0149466
X-RAY DIFFRACTIONf_dihedral_angle_d8.1101403
LS refinement shell
Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkRefine-ID% reflection obs (%)
1.44-1.480.43061240.41413135X-RAY DIFFRACTION90.05
1.48-1.520.37651400.34273371X-RAY DIFFRACTION98.18
1.52-1.560.32421440.28423446X-RAY DIFFRACTION98.3
1.56-1.610.31851400.25953400X-RAY DIFFRACTION98.52
1.61-1.670.23711420.22453454X-RAY DIFFRACTION98.44
1.67-1.740.24631390.21413428X-RAY DIFFRACTION98.43
1.74-1.810.23521430.21163458X-RAY DIFFRACTION99.26
1.81-1.910.26071400.19553484X-RAY DIFFRACTION99.21
1.91-2.030.26541380.18293474X-RAY DIFFRACTION99.26
2.03-2.190.21541470.17593511X-RAY DIFFRACTION99.48
2.19-2.410.19671420.18273526X-RAY DIFFRACTION99.76
2.41-2.750.20591480.18853543X-RAY DIFFRACTION99.78
2.75-3.470.21480.18373589X-RAY DIFFRACTION100
3.47-43.080.17011550.15863745X-RAY DIFFRACTION99.9
Refinement TLS params.Method: refined / Origin x: 11.0999087508 Å / Origin y: -3.40368317935 Å / Origin z: -12.8144037637 Å
111213212223313233
T0.180901596254 Å2-0.00137923487795 Å20.0113927035456 Å2-0.179478651338 Å20.00726724647718 Å2--0.190553701975 Å2
L0.624267043707 °20.0400266031588 °20.168407449377 °2-2.23882068529 °2-0.088692121813 °2--0.505515350512 °2
S0.0281725112531 Å °0.0225970226735 Å °0.0492940324435 Å °0.0707581217982 Å °-0.0426109925166 Å °-0.116715675799 Å °-0.0233269317323 Å °0.095259640944 Å °0.0130654284435 Å °
Refinement TLS groupSelection details: all

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