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- PDB-4yjv: THE KINASE DOMAIN OF HUMAN SPLEEN TYROSINE (SYK) IN COMPLEX WITH ... -

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Basic information

Entry
Database: PDB / ID: 4yjv
TitleTHE KINASE DOMAIN OF HUMAN SPLEEN TYROSINE (SYK) IN COMPLEX WITH GTC000250
ComponentsTyrosine-protein kinase SYK
KeywordsTRANSFERASE / SYK / NON-RECEPTOR TYROSINE KINASE / SPLEEN TYROSINE KINASE / PHOSPHORYLATION / TRANSFERASE-TRANSFERASE INHIBITOR COMPLEX
Function / homology
Function and homology information


interleukin-15 receptor binding / regulation of superoxide anion generation / regulation of neutrophil degranulation / regulation of arachidonate secretion / positive regulation of interleukin-3 production / cellular response to lectin / B cell receptor complex / Toll-like receptor binding / regulation of platelet aggregation / positive regulation of alpha-beta T cell proliferation ...interleukin-15 receptor binding / regulation of superoxide anion generation / regulation of neutrophil degranulation / regulation of arachidonate secretion / positive regulation of interleukin-3 production / cellular response to lectin / B cell receptor complex / Toll-like receptor binding / regulation of platelet aggregation / positive regulation of alpha-beta T cell proliferation / serotonin secretion by platelet / leukocyte activation involved in immune response / neutrophil activation involved in immune response / lymph vessel development / positive regulation of mast cell degranulation / gamma-delta T cell differentiation / positive regulation of mast cell cytokine production / collagen-activated tyrosine kinase receptor signaling pathway / positive regulation of gamma-delta T cell differentiation / cell surface pattern recognition receptor signaling pathway / regulation of platelet activation / cell activation / beta selection / cellular response to molecule of fungal origin / FLT3 signaling through SRC family kinases / early phagosome / leukotriene biosynthetic process / regulation of phagocytosis / regulation of DNA-binding transcription factor activity / regulation of tumor necrosis factor-mediated signaling pathway / macrophage activation involved in immune response / interleukin-3-mediated signaling pathway / positive regulation of bone resorption / positive regulation of monocyte chemotactic protein-1 production / cellular response to lipid / Fc epsilon receptor (FCERI) signaling / Interleukin-2 signaling / positive regulation of granulocyte macrophage colony-stimulating factor production / positive regulation of alpha-beta T cell differentiation / blood vessel morphogenesis / positive regulation of cell adhesion mediated by integrin / positive regulation of B cell differentiation / leukocyte cell-cell adhesion / T cell receptor complex / mast cell degranulation / Dectin-2 family / positive regulation of interleukin-4 production / Fc-epsilon receptor signaling pathway / stimulatory C-type lectin receptor signaling pathway / Fc-gamma receptor signaling pathway involved in phagocytosis / amyloid-beta clearance / positive regulation of interleukin-10 production / positive regulation of receptor internalization / FCGR activation / cellular response to low-density lipoprotein particle stimulus / Role of LAT2/NTAL/LAB on calcium mobilization / positive regulation of type I interferon production / Role of phospholipids in phagocytosis / phosphatase binding / regulation of ERK1 and ERK2 cascade / phospholipase binding / GPVI-mediated activation cascade / Signaling by CSF3 (G-CSF) / positive regulation of superoxide anion generation / phosphotyrosine residue binding / neutrophil chemotaxis / positive regulation of interleukin-12 production / Integrin signaling / positive regulation of TORC1 signaling / FCERI mediated Ca+2 mobilization / SH2 domain binding / positive regulation of calcium-mediated signaling / FCGR3A-mediated IL10 synthesis / Antigen activates B Cell Receptor (BCR) leading to generation of second messengers / peptidyl-tyrosine phosphorylation / B cell differentiation / animal organ morphogenesis / integrin-mediated signaling pathway / positive regulation of interleukin-8 production / B cell receptor signaling pathway / non-membrane spanning protein tyrosine kinase activity / FCGR3A-mediated phagocytosis / FCERI mediated MAPK activation / Regulation of signaling by CBL / non-specific protein-tyrosine kinase / apoptotic signaling pathway / negative regulation of inflammatory response to antigenic stimulus / positive regulation of protein-containing complex assembly / calcium-mediated signaling / Inactivation of CSF3 (G-CSF) signaling / Regulation of actin dynamics for phagocytic cup formation / platelet activation / receptor internalization / positive regulation of interleukin-6 production / CLEC7A (Dectin-1) signaling / integrin binding / cellular response to amyloid-beta / protein import into nucleus / positive regulation of tumor necrosis factor production / kinase activity
Similarity search - Function
Tyrosine-protein kinase, non-receptor SYK/ZAP-70 / Tyrosine-protein kinase SYK/ZAP-70, inter-SH2 domain superfamily / SYK/ZAP-70, N-terminal SH2 domain / : / SH2 domain / Src homology 2 (SH2) domain profile. / Src homology 2 domains / SH2 domain / SH2 domain superfamily / Tyrosine-protein kinase, catalytic domain ...Tyrosine-protein kinase, non-receptor SYK/ZAP-70 / Tyrosine-protein kinase SYK/ZAP-70, inter-SH2 domain superfamily / SYK/ZAP-70, N-terminal SH2 domain / : / SH2 domain / Src homology 2 (SH2) domain profile. / Src homology 2 domains / SH2 domain / SH2 domain superfamily / 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-4DT / Tyrosine-protein kinase SYK
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / FOURIER SYNTHESIS / Resolution: 1.652 Å
AuthorsSomers, D.O. / Neu, M. / Stuckey, J.
Citation
Journal: to be published
Title: THE KINASE DOMAIN OF HUMAN SPLEEN TYROSINE (SYK) IN COMPLEX WITH GTC000250
Authors: Somers, D.O. / Neu, M. / Stuckey, J.
#1: Journal: Bioorg. Med. Chem. Lett. / Year: 2011
Title: Discovery of GSK143, a highly potent, selective and orally efficacious spleen tyrosine kinase inhibitor.
Authors: Liddle, J. / Atkinson, F.L. / Barker, M.D. / Carter, P.S. / Curtis, N.R. / Davis, R.P. / Douault, C. / Dickson, M.C. / Elwes, D. / Garton, N.S. / Gray, M. / Hayhow, T.G. / Hobbs, C.I. / ...Authors: Liddle, J. / Atkinson, F.L. / Barker, M.D. / Carter, P.S. / Curtis, N.R. / Davis, R.P. / Douault, C. / Dickson, M.C. / Elwes, D. / Garton, N.S. / Gray, M. / Hayhow, T.G. / Hobbs, C.I. / Jones, E. / Leach, S. / Leavens, K. / Lewis, H.D. / McCleary, S. / Neu, M. / Patel, V.K. / Preston, A.G. / Ramirez-Molina, C. / Shipley, T.J. / Skone, P.A. / Smithers, N. / Somers, D.O. / Walker, A.L. / Watson, R.J. / Weingarten, G.G.
History
DepositionMar 3, 2015Deposition site: RCSB / Processing site: PDBE
Revision 1.0Oct 14, 2015Provider: repository / Type: Initial release
Revision 1.1May 1, 2024Group: 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
Revision 1.2Nov 20, 2024Group: Structure summary / Category: pdbx_entry_details / pdbx_modification_feature

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Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

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Assembly

Deposited unit
A: Tyrosine-protein kinase SYK
hetero molecules


Theoretical massNumber of molelcules
Total (without water)33,2592
Polymers32,8111
Non-polymers4481
Water6,179343
1


  • Idetical with deposited unit
  • defined by author&software
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area0 Å2
ΔGint0 kcal/mol
Surface area13950 Å2
MethodPISA
Unit cell
Length a, b, c (Å)39.460, 86.940, 40.430
Angle α, β, γ (deg.)90.000, 92.590, 90.000
Int Tables number4
Space group name H-MP1211

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Components

#1: Protein Tyrosine-protein kinase SYK / Spleen tyrosine kinase / p72-Syk


Mass: 32810.605 Da / Num. of mol.: 1 / Fragment: UNP residues 355-635
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: SYK / Cell line (production host): Sf9 / Production host: Spodoptera frugiperda (fall armyworm)
References: UniProt: P43405, non-specific protein-tyrosine kinase
#2: Chemical ChemComp-4DT / 3-[6-({4-[ethyl(1H-indazol-4-yl)amino]-5-fluoropyrimidin-2-yl}amino)-2,4-dihydro-1H-indazol-1-yl]propan-1-ol


Mass: 448.496 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C23H25FN8O
#3: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 343 / Source method: isolated from a natural source / Formula: H2O
Has protein modificationY

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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: 2.12 Å3/Da / Density % sol: 42.03 %
Crystal growTemperature: 293 K / Method: vapor diffusion, hanging drop / pH: 6
Details: 30% Jeffamine ED-2001, 10% Glycerol, 0.1M MES pH6.0, 5mM TCEP

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Data collection

DiffractionMean temperature: 100 K
Diffraction sourceSource: ROTATING ANODE / Type: OTHER / Wavelength: 1.5418 Å
DetectorType: MAR CCD 130 mm / Detector: CCD / Date: Aug 15, 2005
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1.5418 Å / Relative weight: 1
ReflectionResolution: 1.652→27.597 Å / Num. obs: 30428 / % possible obs: 93.1 % / Redundancy: 2.3 % / Biso Wilson estimate: 20.75 Å2 / Rmerge(I) obs: 0.035 / Rsym value: 0.035 / Net I/av σ(I): 6.208 / Net I/σ(I): 22.8 / Num. measured all: 68929
Reflection shell

Diffraction-ID: 1 / Rejects: _

Resolution (Å)Redundancy (%)Rmerge(I) obsMean I/σ(I) obsNum. measured allNum. unique allRsym valueNet I/σ(I) obs% possible all
1.652-1.742.10.1224.9835839440.1227.883.3
1.74-1.842.30.0748.5929941190.0741291.3
1.84-1.972.30.04912.3884339120.04917.492.7
1.97-2.132.30.03715.7851637480.03722.594.3
2.13-2.332.30.0379.4794434430.03726.295.2
2.33-2.612.30.0339.3731131360.0332996
2.61-3.012.30.0329.9657028340.03231.397.2
3.01-3.692.30.0338.7557824290.03334.798.3
3.69-5.222.30.0310.5425618560.033797.8
5.22-27.5972.20.0358.2225410070.03536.494

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Processing

Software
NameVersionClassification
MOSFLM6.2.4data reduction
SCALA3.2.5data scaling
BUSTER2.11.2refinement
PDB_EXTRACT3.15data extraction
RefinementMethod to determine structure: FOURIER SYNTHESIS
Starting model: In-house SYK model

Resolution: 1.652→27.59 Å / Cor.coef. Fo:Fc: 0.9534 / Cor.coef. Fo:Fc free: 0.9136 / SU R Cruickshank DPI: 0.106 / Cross valid method: THROUGHOUT / σ(F): 0 / SU R Blow DPI: 0.112 / SU Rfree Blow DPI: 0.113 / SU Rfree Cruickshank DPI: 0.109
RfactorNum. reflection% reflectionSelection details
Rfree0.2223 1537 5.06 %RANDOM
Rwork0.1748 ---
obs0.1773 30403 92.84 %-
Displacement parametersBiso max: 105.56 Å2 / Biso mean: 23.68 Å2 / Biso min: 6.86 Å2
Baniso -1Baniso -2Baniso -3
1--1.3644 Å20 Å20.1907 Å2
2--1.7569 Å20 Å2
3----0.3925 Å2
Refine analyzeLuzzati coordinate error obs: 0.181 Å
Refinement stepCycle: final / Resolution: 1.652→27.59 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms2172 0 33 343 2548
Biso mean--20.51 34.5 -
Num. residues----265
Refine LS restraints
Refine-IDTypeNumberRestraint functionWeightDev ideal
X-RAY DIFFRACTIONt_dihedral_angle_d1065SINUSOIDAL2
X-RAY DIFFRACTIONt_trig_c_planes59HARMONIC2
X-RAY DIFFRACTIONt_gen_planes328HARMONIC5
X-RAY DIFFRACTIONt_it2321HARMONIC20
X-RAY DIFFRACTIONt_nbd
X-RAY DIFFRACTIONt_improper_torsion
X-RAY DIFFRACTIONt_pseud_angle
X-RAY DIFFRACTIONt_chiral_improper_torsion267SEMIHARMONIC5
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_contact3008SEMIHARMONIC4
X-RAY DIFFRACTIONt_bond_d2321HARMONIC20.01
X-RAY DIFFRACTIONt_angle_deg3158HARMONIC20.98
X-RAY DIFFRACTIONt_omega_torsion3.76
X-RAY DIFFRACTIONt_other_torsion2.82
LS refinement shellResolution: 1.65→1.71 Å / Total num. of bins used: 15
RfactorNum. reflection% reflection
Rfree0.2609 112 4.4 %
Rwork0.2254 2435 -
all0.227 2547 -
obs--92.84 %
Refinement TLS params.Method: refined / Origin x: 33.2682 Å / Origin y: 27.4431 Å / Origin z: 36.5395 Å
111213212223313233
T-0.0316 Å2-0.0025 Å20.0152 Å2--0.0233 Å2-0.0213 Å2---0.0511 Å2
L0.4784 °2-0.3559 °20.1758 °2-0.9678 °2-0.0784 °2--0.6248 °2
S-0.0091 Å °0.0158 Å °-0.0165 Å °0.035 Å °-0.0165 Å °-0.0416 Å °-0.0433 Å °-0.0068 Å °0.0256 Å °
Refinement TLS groupSelection details: {A|*}

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