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- PDB-5zj6: Crystal structure of HCK kinase complexed with a pyrrolo-pyrimidi... -

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Basic information

Entry
Database: PDB / ID: 5zj6
TitleCrystal structure of HCK kinase complexed with a pyrrolo-pyrimidine inhibitor 7-[trans-4-(4-methylpiperazin-1-yl)cyclohexyl]-5-(4-phenoxyphenyl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine
ComponentsTyrosine-protein kinase HCK
KeywordsTRANSFERASE / kinase/Kinase inhibitor
Function / homology
Function and homology information


leukocyte degranulation / innate immune response-activating signaling pathway / respiratory burst after phagocytosis / leukocyte migration involved in immune response / regulation of podosome assembly / FLT3 signaling through SRC family kinases / regulation of phagocytosis / Nef and signal transduction / regulation of DNA-binding transcription factor activity / positive regulation of actin filament polymerization ...leukocyte degranulation / innate immune response-activating signaling pathway / respiratory burst after phagocytosis / leukocyte migration involved in immune response / regulation of podosome assembly / FLT3 signaling through SRC family kinases / regulation of phagocytosis / Nef and signal transduction / regulation of DNA-binding transcription factor activity / positive regulation of actin filament polymerization / Fc-gamma receptor signaling pathway involved in phagocytosis / mesoderm development / FCGR activation / type II interferon-mediated signaling pathway / Signaling by CSF3 (G-CSF) / transport vesicle / phosphotyrosine residue binding / FCGR3A-mediated IL10 synthesis / lipopolysaccharide-mediated signaling pathway / cell surface receptor protein tyrosine kinase signaling pathway / integrin-mediated signaling pathway / cell projection / non-membrane spanning protein tyrosine kinase activity / regulation of actin cytoskeleton organization / FCGR3A-mediated phagocytosis / Regulation of signaling by CBL / non-specific protein-tyrosine kinase / negative regulation of inflammatory response to antigenic stimulus / cytokine-mediated signaling pathway / Inactivation of CSF3 (G-CSF) signaling / peptidyl-tyrosine phosphorylation / caveola / cytoplasmic side of plasma membrane / Signaling by CSF1 (M-CSF) in myeloid cells / regulation of cell shape / protein autophosphorylation / regulation of inflammatory response / protein tyrosine kinase activity / cell differentiation / cytoskeleton / lysosome / cell adhesion / intracellular signal transduction / protein phosphorylation / inflammatory response / signaling receptor binding / focal adhesion / intracellular membrane-bounded organelle / positive regulation of cell population proliferation / lipid binding / negative regulation of apoptotic process / Golgi apparatus / ATP binding / nucleus / plasma membrane / cytosol
Similarity search - Function
Tyrosine-protein kinase HCK, SH2 domain / : / SH3 domain / SH2 domain / Src homology 2 (SH2) domain profile. / Src homology 2 domains / SH2 domain / SH2 domain superfamily / Src homology 3 domains / SH3-like domain superfamily ...Tyrosine-protein kinase HCK, SH2 domain / : / SH3 domain / SH2 domain / Src homology 2 (SH2) domain profile. / Src homology 2 domains / SH2 domain / SH2 domain superfamily / Src homology 3 domains / SH3-like domain superfamily / Src homology 3 (SH3) domain profile. / SH3 domain / Tyrosine-protein kinase, catalytic domain / Tyrosine kinase, catalytic domain / Tyrosine protein kinases specific active-site signature. / Tyrosine-protein kinase, active site / Serine-threonine/tyrosine-protein kinase, catalytic domain / Protein tyrosine and serine/threonine kinase / Phosphorylase Kinase; domain 1 / Phosphorylase Kinase; domain 1 / Transferase(Phosphotransferase) domain 1 / Transferase(Phosphotransferase); domain 1 / 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-VSE / Tyrosine-protein kinase HCK
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / molecular replacement / Resolution: 1.696 Å
AuthorsTomabechi, Y. / Kukimoto-Niino, M. / Shirouzu, M.
CitationJournal: Protein Expr. Purif. / Year: 2018
Title: Phosphorylated and non-phosphorylated HCK kinase domains produced by cell-free protein expression.
Authors: Katsura, K. / Tomabechi, Y. / Matsuda, T. / Yonemochi, M. / Mikuni, J. / Ohsawa, N. / Terada, T. / Yokoyama, S. / Kukimoto-Niino, M. / Takemoto, C. / Shirouzu, M.
History
DepositionMar 19, 2018Deposition site: PDBJ / Processing site: PDBJ
Revision 1.0Jun 6, 2018Provider: repository / Type: Initial release
Revision 1.1Jun 13, 2018Group: Data collection / Database references / Category: citation
Item: _citation.journal_volume / _citation.page_first / _citation.page_last
Revision 1.2Nov 22, 2023Group: Data collection / Database references / Refinement description
Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / database_2 / pdbx_initial_refinement_model
Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession

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Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

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Assembly

Deposited unit
A: Tyrosine-protein kinase HCK
B: Tyrosine-protein kinase HCK
hetero molecules


Theoretical massNumber of molelcules
Total (without water)66,1704
Polymers65,2052
Non-polymers9652
Water12,178676
1


  • Idetical with deposited unit
  • defined by author
  • Evidence: gel filtration
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area1540 Å2
ΔGint-4 kcal/mol
Surface area24180 Å2
Unit cell
Length a, b, c (Å)42.810, 48.020, 78.010
Angle α, β, γ (deg.)87.590, 83.090, 63.590
Int Tables number1
Space group name H-MP1

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Components

#1: Protein Tyrosine-protein kinase HCK / Hematopoietic cell kinase / Hemopoietic cell kinase / p59-HCK/p60-HCK / p59Hck / p61Hck


Mass: 32602.527 Da / Num. of mol.: 2
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: HCK / Production host: Spodoptera frugiperda (fall armyworm)
References: UniProt: P08631, non-specific protein-tyrosine kinase
#2: Chemical ChemComp-VSE / 7-[trans-4-(4-methylpiperazin-1-yl)cyclohexyl]-5-(4-phenoxyphenyl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine


Mass: 482.620 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C29H34N6O
#3: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 676 / Source method: isolated from a natural source / Formula: H2O

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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: 2.19 Å3/Da / Density % sol: 43.75 %
Crystal growTemperature: 288 K / Method: vapor diffusion, sitting drop / Details: 0.1 M Tris-HCl (pH 8.5) 25 % (v/v) PEG 10,000

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Data collection

DiffractionMean temperature: 100 K
Diffraction sourceSource: SYNCHROTRON / Site: SPring-8 / Beamline: BL26B2 / Wavelength: 1 Å
DetectorType: MARMOSAIC 225 mm CCD / Detector: CCD / Date: Oct 6, 2014
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1 Å / Relative weight: 1
ReflectionResolution: 1.696→38.094 Å / Num. obs: 56349 / % possible obs: 92.1 % / Redundancy: 1.989 % / CC1/2: 0.995 / Rmerge(I) obs: 0.06 / Rrim(I) all: 0.085 / Χ2: 1.024 / Net I/σ(I): 8.4 / Num. measured all: 112062
Reflection shell

Diffraction-ID: 1

Resolution (Å)Redundancy (%)Rmerge(I) obsMean I/σ(I) obsNum. measured obsNum. possibleNum. unique obsCC1/2Rrim(I) all% possible all
1.7-1.81.9540.4521.6717377988288950.7250.63890
1.8-1.921.9960.272.917074931285540.8790.38291.9
1.92-2.081.9940.1574.915562862878040.9520.22290.4
2.08-2.271.9950.0997.4514442800572380.9770.1490.4
2.27-2.541.9970.06910.1713348717566830.9860.09793.1
2.54-2.931.9950.05412.5611834631659320.990.07793.9
2.93-3.591.9950.03916.1710268540651460.9940.05595.2
3.59-5.061.9960.03718.937760414638870.9930.05293.8
5.06-38.0941.990.03219.144397231522100.9960.04595.5

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Phasing

PhasingMethod: molecular replacement
Phasing MR
Highest resolutionLowest resolution
Rotation6.37 Å43 Å
Translation6.37 Å43 Å

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Processing

Software
NameVersionClassificationNB
XDSdata reduction
XSCALEdata scaling
PHASER2.8.0phasing
PHENIX1.12_2829refinement
PDB_EXTRACT3.24data extraction
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 2HK5

2hk5


Resolution: 1.696→38.094 Å / SU ML: 0.24 / Cross valid method: THROUGHOUT / σ(F): 1.98 / Phase error: 25.87 / Stereochemistry target values: ML
RfactorNum. reflection% reflection
Rfree0.2401 2005 3.56 %
Rwork0.2066 54322 -
obs0.2078 56327 92.04 %
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT BULK SOLVENT MODEL
Displacement parametersBiso max: 103.51 Å2 / Biso mean: 21.5299 Å2 / Biso min: 5.64 Å2
Refinement stepCycle: final / Resolution: 1.696→38.094 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms4353 0 72 676 5101
Biso mean--14.79 29.36 -
Num. residues----541
Refine LS restraints
Refine-IDTypeDev idealNumber
X-RAY DIFFRACTIONf_bond_d0.0044543
X-RAY DIFFRACTIONf_angle_d0.6566148
X-RAY DIFFRACTIONf_chiral_restr0.047659
X-RAY DIFFRACTIONf_plane_restr0.004774
X-RAY DIFFRACTIONf_dihedral_angle_d11.7962743
LS refinement shell

Refine-ID: X-RAY DIFFRACTION / Rfactor Rfree error: 0 / Total num. of bins used: 14

Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkNum. reflection all% reflection obs (%)
1.696-1.73840.35941290.29173552368185
1.7384-1.78540.32281530.28163985413893
1.7854-1.8380.32611350.27263910404593
1.838-1.89730.27151410.24893849399092
1.8973-1.96510.25651400.22623785392590
1.9651-2.04380.2571410.21223889403091
2.0438-2.13680.24921450.21413783392890
2.1368-2.24940.25161420.20733798394091
2.2494-2.39030.26261480.20073896404492
2.3903-2.57490.23961410.20693933407494
2.5749-2.83390.23751490.21263977412694
2.8339-3.24380.24031440.20054009415395
3.2438-4.08610.20951460.17493955410194
4.0861-38.10370.19851510.19254001415295

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