[English] 日本語
Yorodumi
- PDB-4xg7: Crystal structure of an inhibitor-bound Syk -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 4xg7
TitleCrystal structure of an inhibitor-bound Syk
ComponentsTyrosine-protein kinase SYK
KeywordsTRANSFERASE/TRANSFERASE INHIBITOR / Syk kinase / Inhibitor / Spleen tyrosine kinase / TRANSFERASE-TRANSFERASE INHIBITOR complex
Function / homology
Function and homology information


serotonin secretion by platelet / interleukin-15 receptor binding / positive regulation of interleukin-3 production / regulation of superoxide anion generation / regulation of neutrophil degranulation / regulation of arachidonic acid secretion / cellular response to lectin / gamma-delta T cell differentiation / positive regulation of gamma-delta T cell differentiation / B cell receptor complex ...serotonin secretion by platelet / interleukin-15 receptor binding / positive regulation of interleukin-3 production / regulation of superoxide anion generation / regulation of neutrophil degranulation / regulation of arachidonic acid secretion / cellular response to lectin / gamma-delta T cell differentiation / positive regulation of gamma-delta T cell differentiation / B cell receptor complex / neutrophil activation involved in immune response / Toll-like receptor binding / regulation of platelet aggregation / positive regulation of alpha-beta T cell proliferation / leukocyte activation involved in immune response / positive regulation of mast cell cytokine production / regulation of platelet activation / lymph vessel development / collagen-activated tyrosine kinase receptor signaling pathway / cell activation / positive regulation of mast cell degranulation / macrophage activation involved in immune response / beta selection / regulation of phagocytosis / positive regulation of killing of cells of another organism / cellular response to molecule of fungal origin / regulation of tumor necrosis factor-mediated signaling pathway / leukotriene biosynthetic process / FLT3 signaling through SRC family kinases / early phagosome / positive regulation of monocyte chemotactic protein-1 production / interleukin-3-mediated signaling pathway / cellular response to lipid / positive regulation of granulocyte macrophage colony-stimulating factor production / positive regulation of cell adhesion mediated by integrin / regulation of DNA-binding transcription factor activity / Fc epsilon receptor (FCERI) signaling / Interleukin-2 signaling / positive regulation of alpha-beta T cell differentiation / blood vessel morphogenesis / T cell receptor complex / positive regulation of B cell differentiation / leukocyte cell-cell adhesion / mast cell degranulation / Fc-gamma receptor signaling pathway involved in phagocytosis / Dectin-2 family / Fc-epsilon receptor signaling pathway / stimulatory C-type lectin receptor signaling pathway / phospholipase binding / positive regulation of cysteine-type endopeptidase activity involved in apoptotic process / positive regulation of interleukin-10 production / positive regulation of receptor internalization / cellular response to low-density lipoprotein particle stimulus / FCGR activation / positive regulation of type I interferon production / positive regulation of interleukin-4 production / positive regulation of bone resorption / phosphatase binding / Role of phospholipids in phagocytosis / Role of LAT2/NTAL/LAB on calcium mobilization / positive regulation of calcium-mediated signaling / Signaling by CSF3 (G-CSF) / negative regulation of inflammatory response to antigenic stimulus / GPVI-mediated activation cascade / positive regulation of TORC1 signaling / extrinsic component of cytoplasmic side of plasma membrane / positive regulation of interleukin-12 production / SH2 domain binding / phosphotyrosine residue binding / Integrin signaling / FCERI mediated Ca+2 mobilization / FCGR3A-mediated IL10 synthesis / regulation of ERK1 and ERK2 cascade / B cell differentiation / neutrophil chemotaxis / positive regulation of superoxide anion generation / Antigen activates B Cell Receptor (BCR) leading to generation of second messengers / integrin-mediated signaling pathway / positive regulation of interleukin-8 production / calcium-mediated signaling / Regulation of signaling by CBL / positive regulation of protein-containing complex assembly / FCGR3A-mediated phagocytosis / FCERI mediated MAPK activation / animal organ morphogenesis / B cell receptor signaling pathway / non-specific protein-tyrosine kinase / non-membrane spanning protein tyrosine kinase activity / Inactivation of CSF3 (G-CSF) signaling / receptor internalization / Regulation of actin dynamics for phagocytic cup formation / CLEC7A (Dectin-1) signaling / platelet activation / positive regulation of interleukin-6 production / protein import into nucleus / peptidyl-tyrosine phosphorylation / cell surface receptor protein tyrosine kinase signaling pathway / positive regulation of peptidyl-tyrosine phosphorylation / integrin binding / positive regulation of tumor necrosis factor production
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 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 / Protein tyrosine and serine/threonine kinase / Serine-threonine/tyrosine-protein kinase, catalytic domain / Transferase(Phosphotransferase) domain 1 / Transferase(Phosphotransferase); domain 1 / Phosphorylase Kinase; domain 1 / Phosphorylase Kinase; 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-X7G / Tyrosine-protein kinase SYK
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 1.76 Å
AuthorsLee, S.J. / Choi, J. / Han, B.G. / Song, H. / Koh, J.S. / Lee, B.I.
CitationJournal: Febs J. / Year: 2016
Title: Crystal structures of spleen tyrosine kinase in complex with novel inhibitors: structural insights for design of anticancer drugs
Authors: Lee, S.J. / Choi, J.S. / Han, B.G. / Kim, H.S. / Song, H.J. / Lee, J. / Nam, S. / Goh, S.H. / Kim, J.H. / Koh, J.S. / Lee, B.I.
History
DepositionDec 30, 2014Deposition site: RCSB / Processing site: PDBJ
Revision 1.0Dec 30, 2015Provider: repository / Type: Initial release
Revision 1.1Aug 31, 2016Group: Database references
Revision 1.2Oct 19, 2016Group: Database references
Revision 1.3Feb 5, 2020Group: Data collection / Derived calculations / Category: diffrn_source / pdbx_struct_oper_list
Item: _diffrn_source.pdbx_synchrotron_site / _pdbx_struct_oper_list.symmetry_operation
Revision 1.4Nov 8, 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

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Tyrosine-protein kinase SYK
hetero molecules


Theoretical massNumber of molelcules
Total (without water)34,2912
Polymers33,9011
Non-polymers3901
Water3,513195
1


  • Idetical with deposited unit
  • defined by author
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area0 Å2
ΔGint0 kcal/mol
Surface area13540 Å2
Unit cell
Length a, b, c (Å)39.901, 88.187, 40.982
Angle α, β, γ (deg.)90.00, 91.12, 90.00
Int Tables number4
Space group name H-MP1211

-
Components

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


Mass: 33900.965 Da / Num. of mol.: 1 / Fragment: protein kinase domain, residues 356-635
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: SYK / Plasmid: pVL1393 / Production host: Spodoptera frugiperda (fall armyworm)
References: UniProt: P43405, non-specific protein-tyrosine kinase
#2: Chemical ChemComp-X7G / 1-[(3-methyl-1-{2-[(1-methyl-1H-indazol-5-yl)amino]pyrimidin-4-yl}-1H-pyrazol-4-yl)methyl]azetidin-3-ol


Mass: 390.442 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C20H22N8O
#3: Water ChemComp-HOH / water / Water


Mass: 18.015 Da / Num. of mol.: 195 / Source method: isolated from a natural source / Formula: H2O

-
Experimental details

-
Experiment

ExperimentMethod: X-RAY DIFFRACTION

-
Sample preparation

CrystalDensity Matthews: 2.13 Å3/Da / Density % sol: 42.16 %
Crystal growTemperature: 278 K / Method: vapor diffusion, hanging drop / pH: 8.5 / Details: 10~20%(v/v) PEG3350, 100 mM Tris-HCl

-
Data collection

DiffractionMean temperature: 100 K
Diffraction sourceSource: SYNCHROTRON / Site: SPring-8 / Beamline: BL44XU / Wavelength: 0.9 Å
DetectorType: RAYONIX MX300HE / Detector: CCD / Date: Jun 29, 2011
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.9 Å / Relative weight: 1
ReflectionResolution: 1.76→50 Å / Num. obs: 27304 / % possible obs: 97.4 % / Redundancy: 6.2 % / Net I/σ(I): 58.15
Reflection shellResolution: 1.76→1.79 Å

-
Processing

Software
NameVersionClassification
REFMAC5.8.0103refinement
HKL-2000data reduction
HKL-2000data scaling
MOLREPphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 4XG2

4xg2


Resolution: 1.76→44.09 Å / Cor.coef. Fo:Fc: 0.949 / Cor.coef. Fo:Fc free: 0.914 / SU B: 5.791 / SU ML: 0.084 / Cross valid method: THROUGHOUT / ESU R: 0.265 / ESU R Free: 0.127 / Stereochemistry target values: MAXIMUM LIKELIHOOD / Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS
RfactorNum. reflection% reflectionSelection details
Rfree0.24246 1443 5.3 %RANDOM
Rwork0.22287 ---
obs0.22607 25832 97.18 %-
Solvent computationIon probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.2 Å / Solvent model: MASK
Displacement parametersBiso mean: 33.304 Å2
Baniso -1Baniso -2Baniso -3
1--0.27 Å2-0 Å2-0.87 Å2
2---1.21 Å20 Å2
3---1.5 Å2
Refinement stepCycle: LAST / Resolution: 1.76→44.09 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms2171 0 29 195 2395
Refine LS restraints
Refine-IDTypeDev idealDev ideal targetNumber
X-RAY DIFFRACTIONr_bond_refined_d0.0070.0192272
X-RAY DIFFRACTIONr_bond_other_d0.0020.022183
X-RAY DIFFRACTIONr_angle_refined_deg1.2621.9773066
X-RAY DIFFRACTIONr_angle_other_deg0.8953.0014999
X-RAY DIFFRACTIONr_dihedral_angle_1_deg5.7565266
X-RAY DIFFRACTIONr_dihedral_angle_2_deg34.38624.095105
X-RAY DIFFRACTIONr_dihedral_angle_3_deg12.5715419
X-RAY DIFFRACTIONr_dihedral_angle_4_deg14.5831513
X-RAY DIFFRACTIONr_chiral_restr0.0710.2322
X-RAY DIFFRACTIONr_gen_planes_refined0.0040.022512
X-RAY DIFFRACTIONr_gen_planes_other0.0010.02518
X-RAY DIFFRACTIONr_nbd_refined
X-RAY DIFFRACTIONr_nbd_other
X-RAY DIFFRACTIONr_nbtor_refined
X-RAY DIFFRACTIONr_nbtor_other
X-RAY DIFFRACTIONr_xyhbond_nbd_refined
X-RAY DIFFRACTIONr_xyhbond_nbd_other
X-RAY DIFFRACTIONr_metal_ion_refined
X-RAY DIFFRACTIONr_metal_ion_other
X-RAY DIFFRACTIONr_symmetry_vdw_refined
X-RAY DIFFRACTIONr_symmetry_vdw_other
X-RAY DIFFRACTIONr_symmetry_hbond_refined
X-RAY DIFFRACTIONr_symmetry_hbond_other
X-RAY DIFFRACTIONr_symmetry_metal_ion_refined
X-RAY DIFFRACTIONr_symmetry_metal_ion_other
X-RAY DIFFRACTIONr_mcbond_it1.8363.1161067
X-RAY DIFFRACTIONr_mcbond_other1.8163.1131066
X-RAY DIFFRACTIONr_mcangle_it2.2434.6541329
X-RAY DIFFRACTIONr_mcangle_other2.2424.6581330
X-RAY DIFFRACTIONr_scbond_it1.573.4031205
X-RAY DIFFRACTIONr_scbond_other1.573.4031206
X-RAY DIFFRACTIONr_scangle_it
X-RAY DIFFRACTIONr_scangle_other1.8225.011735
X-RAY DIFFRACTIONr_long_range_B_refined3.01625.5812756
X-RAY DIFFRACTIONr_long_range_B_other2.65425.1352672
X-RAY DIFFRACTIONr_rigid_bond_restr
X-RAY DIFFRACTIONr_sphericity_free
X-RAY DIFFRACTIONr_sphericity_bonded
LS refinement shellResolution: 1.761→1.807 Å / Total num. of bins used: 20
RfactorNum. reflection% reflection
Rfree0.253 96 -
Rwork0.196 1933 -
obs--97.64 %

+
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