[English] 日本語
Yorodumi
- PDB-4wnm: SYK catalytic domain in complex with a potent triazolopyridine in... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 4wnm
TitleSYK catalytic domain in complex with a potent triazolopyridine inhibitor
ComponentsTyrosine-protein kinase SYK
KeywordsTRANSFERASE/TRANSFERASE INHIBITOR / SYK catalytic domain in complex with a potent triazolopyridine based inhibitor / 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 / leukotriene biosynthetic process / early phagosome / regulation of phagocytosis / : / macrophage activation involved in immune response / interleukin-3-mediated signaling pathway / regulation of tumor necrosis factor-mediated signaling pathway / positive regulation of bone resorption / positive regulation of monocyte chemotactic protein-1 production / Fc epsilon receptor (FCERI) signaling / Interleukin-2 signaling / cellular response to lipid / 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 / mast cell degranulation / T cell receptor complex / 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 / FCGR activation / positive regulation of interleukin-10 production / positive regulation of receptor internalization / 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 / positive regulation of superoxide anion generation / Signaling by CSF3 (G-CSF) / phosphotyrosine residue binding / Integrin signaling / neutrophil chemotaxis / positive regulation of interleukin-12 production / positive regulation of TORC1 signaling / FCERI mediated Ca+2 mobilization / positive regulation of calcium-mediated signaling / FCGR3A-mediated IL10 synthesis / SH2 domain binding / 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 / B cell receptor signaling pathway / positive regulation of interleukin-8 production / non-membrane spanning protein tyrosine kinase activity / FCGR3A-mediated phagocytosis / FCERI mediated MAPK activation / non-specific protein-tyrosine kinase / Regulation of signaling by CBL / 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 / platelet activation / Regulation of actin dynamics for phagocytic cup formation / 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-3RT / Tyrosine-protein kinase SYK
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / Resolution: 2.5 Å
AuthorsJackson, P.J.
CitationJournal: Plos One / Year: 2016
Title: A Novel Triazolopyridine-Based Spleen Tyrosine Kinase Inhibitor That Arrests Joint Inflammation.
Authors: Ferguson, G.D. / Delgado, M. / Plantevin-Krenitsky, V. / Jensen-Pergakes, K. / Bates, R.J. / Torres, S. / Celeridad, M. / Brown, H. / Burnett, K. / Nadolny, L. / Tehrani, L. / Packard, G. / ...Authors: Ferguson, G.D. / Delgado, M. / Plantevin-Krenitsky, V. / Jensen-Pergakes, K. / Bates, R.J. / Torres, S. / Celeridad, M. / Brown, H. / Burnett, K. / Nadolny, L. / Tehrani, L. / Packard, G. / Pagarigan, B. / Haelewyn, J. / Nguyen, T. / Xu, L. / Tang, Y. / Hickman, M. / Baculi, F. / Pierce, S. / Miyazawa, K. / Jackson, P. / Chamberlain, P. / LeBrun, L. / Xie, W. / Bennett, B. / Blease, K.
History
DepositionOct 13, 2014Deposition site: RCSB / Processing site: RCSB
Revision 1.0Jan 20, 2016Provider: repository / Type: Initial release
Revision 1.1Dec 27, 2023Group: Data collection / Database references / Derived calculations
Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / database_2 / pdbx_struct_oper_list
Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession / _pdbx_struct_oper_list.symmetry_operation

-
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)35,4253
Polymers34,8811
Non-polymers5442
Water28816
1


  • Idetical with deposited unit
  • defined by author&software
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area220 Å2
ΔGint-15 kcal/mol
Surface area12920 Å2
MethodPISA
Unit cell
Length a, b, c (Å)39.871, 84.820, 90.627
Angle α, β, γ (deg.)90.000, 90.000, 90.000
Int Tables number19
Space group name H-MP212121

-
Components

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


Mass: 34880.969 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: SYK / Production host: Spodoptera frugiperda (fall armyworm)
References: UniProt: P43405, non-specific protein-tyrosine kinase
#2: Chemical ChemComp-3RT / N~3~-(tetrahydro-2H-pyran-4-yl)-N~6~-[5-(tetrahydro-2H-pyran-4-ylmethyl)[1,2,4]triazolo[1,5-a]pyridin-2-yl]-1H-indazole-3,6-diamine


Mass: 447.533 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C24H29N7O2
#3: Chemical ChemComp-SO4 / SULFATE ION


Mass: 96.063 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: SO4
#4: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 16 / Source method: isolated from a natural source / Formula: H2O

-
Experimental details

-
Experiment

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

-
Sample preparation

CrystalDensity Matthews: 2.2 Å3/Da / Density % sol: 44.01 %
Crystal growTemperature: 278 K / Method: vapor diffusion, sitting drop
Details: 100 mM MES pH 5.3, 150 mM Ammonium sulfate, and 22% PEG 3350

-
Data collection

DiffractionMean temperature: 100 K
Diffraction sourceSource: SYNCHROTRON / Site: ALS / Beamline: 5.0.2 / Wavelength: 1 Å
DetectorType: ADSC QUANTUM 315r / Detector: CCD / Date: Sep 22, 2010
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1 Å / Relative weight: 1
ReflectionResolution: 2.5→50 Å / Num. obs: 9994 / % possible obs: 88.9 % / Redundancy: 2.4 % / Rmerge(I) obs: 0.082 / Χ2: 2.159 / Net I/av σ(I): 16.014 / Net I/σ(I): 11.2 / Num. measured all: 24433
Reflection shell

Diffraction-ID: 1 / Rejects: _

Resolution (Å)Redundancy (%)Rmerge(I) obsNum. unique allΧ2% possible all
2.5-2.542.40.764881.23888.6
2.54-2.592.40.5324881.22889.9
2.59-2.642.40.4514991.15591.2
2.64-2.692.40.4144961.27490.7
2.69-2.752.40.3074861.42389.7
2.75-2.822.40.2975101.46991.7
2.82-2.892.50.2524991.46191.6
2.89-2.962.40.2184991.54890.2
2.96-3.052.40.1795131.8691.4
3.05-3.152.50.145002.05990.7
3.15-3.262.40.1275142.12691.5
3.26-3.392.40.1094902.38490.4
3.39-3.552.50.15202.66891.1
3.55-3.732.40.0774933.11689
3.73-3.972.40.0695103.03189
3.97-4.272.40.0574882.64887.5
4.27-4.72.40.0534963.24986.6
4.7-5.382.50.0534882.99585
5.38-6.782.60.0545072.81184.9
6.78-502.50.0425103.12778.8

-
Processing

Software
NameVersionClassification
HKL-2000data reduction
REFMAC5.8.0049refinement
PDB_EXTRACT3.15data extraction
RefinementResolution: 2.5→50 Å / Cor.coef. Fo:Fc: 0.945 / Cor.coef. Fo:Fc free: 0.918 / SU B: 13.091 / SU ML: 0.272 / Cross valid method: THROUGHOUT / σ(F): 0 / ESU R: 1.041 / ESU R Free: 0.332 / Stereochemistry target values: MAXIMUM LIKELIHOOD
Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS U VALUES : REFINED INDIVIDUALLY
RfactorNum. reflection% reflectionSelection details
Rfree0.26 475 4.8 %RANDOM
Rwork0.2039 9503 --
obs0.2067 9503 88.88 %-
Solvent computationIon probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.2 Å / Solvent model: MASK
Displacement parametersBiso max: 116.85 Å2 / Biso mean: 48.453 Å2 / Biso min: 24.17 Å2
Baniso -1Baniso -2Baniso -3
1--0.02 Å20 Å2-0 Å2
2---0.01 Å20 Å2
3---0.03 Å2
Refinement stepCycle: final / Resolution: 2.5→50 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms2172 0 38 16 2226
Biso mean--47.59 38.74 -
Num. residues----273
Refine LS restraints
Refine-IDTypeDev idealDev ideal targetNumber
X-RAY DIFFRACTIONr_bond_refined_d0.0130.022265
X-RAY DIFFRACTIONr_bond_other_d0.0010.022105
X-RAY DIFFRACTIONr_angle_refined_deg1.5171.943066
X-RAY DIFFRACTIONr_angle_other_deg0.81934787
X-RAY DIFFRACTIONr_dihedral_angle_1_deg6.8925270
X-RAY DIFFRACTIONr_dihedral_angle_2_deg40.54223.981103
X-RAY DIFFRACTIONr_dihedral_angle_3_deg16.49415378
X-RAY DIFFRACTIONr_dihedral_angle_4_deg22.0631512
X-RAY DIFFRACTIONr_chiral_restr0.0850.2324
X-RAY DIFFRACTIONr_gen_planes_refined0.0060.022543
X-RAY DIFFRACTIONr_gen_planes_other0.0010.02530
X-RAY DIFFRACTIONr_mcbond_it3.2854.721088
X-RAY DIFFRACTIONr_mcbond_other3.2814.721088
X-RAY DIFFRACTIONr_mcangle_it5.0217.0641355
LS refinement shellResolution: 2.496→2.56 Å / Total num. of bins used: 20
RfactorNum. reflection% reflection
Rfree0.401 37 -
Rwork0.326 653 -
all-690 -
obs--87.01 %

+
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