[English] 日本語
Yorodumi
- PDB-4px6: SYK catalytic domain in complex with a potent pyridopyrimidinone ... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 4px6
TitleSYK catalytic domain in complex with a potent pyridopyrimidinone inhibitor
ComponentsTyrosine-protein kinase SYK
Keywordstransferase/transferase inhibitor / kinase domain / phosphotransferase / 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 / cellular response to lectin / positive regulation of interleukin-3 production / 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 / regulation of superoxide anion generation / regulation of neutrophil degranulation / regulation of arachidonate secretion / cellular response to lectin / positive regulation of interleukin-3 production / gamma-delta T cell differentiation / positive regulation of gamma-delta T cell differentiation / B cell receptor complex / serotonin secretion by platelet / Toll-like receptor binding / regulation of platelet aggregation / positive regulation of alpha-beta T cell proliferation / leukocyte activation involved in immune response / neutrophil activation involved in immune response / positive regulation of mast cell cytokine production / positive regulation of mast cell degranulation / lymph vessel development / collagen-activated tyrosine kinase receptor signaling pathway / regulation of platelet activation / cell activation / positive regulation of killing of cells of another organism / beta selection / regulation of phagocytosis / cellular response to molecule of fungal origin / macrophage activation involved in immune response / early phagosome / FLT3 signaling through SRC family kinases / leukotriene biosynthetic process / regulation of tumor necrosis factor-mediated signaling pathway / positive regulation of monocyte chemotactic protein-1 production / interleukin-3-mediated signaling pathway / cellular response to lipid / regulation of DNA-binding transcription factor activity / positive regulation of cell adhesion mediated by integrin / Fc epsilon receptor (FCERI) signaling / positive regulation of granulocyte macrophage colony-stimulating factor production / Interleukin-2 signaling / positive regulation of alpha-beta T cell differentiation / blood vessel morphogenesis / positive regulation of B cell differentiation / T cell receptor complex / leukocyte cell-cell adhesion / Fc-gamma receptor signaling pathway involved in phagocytosis / mast cell degranulation / Dectin-2 family / positive regulation of interleukin-4 production / : / stimulatory C-type lectin receptor signaling pathway / Fc-epsilon receptor signaling pathway / phospholipase binding / amyloid-beta clearance / positive regulation of receptor internalization / positive regulation of interleukin-10 production / cellular response to low-density lipoprotein particle stimulus / FCGR activation / positive regulation of type I interferon production / positive regulation of bone resorption / Role of phospholipids in phagocytosis / Role of LAT2/NTAL/LAB on calcium mobilization / phosphatase binding / Signaling by CSF3 (G-CSF) / cell surface receptor protein tyrosine kinase signaling pathway / GPVI-mediated activation cascade / positive regulation of interleukin-12 production / neutrophil chemotaxis / positive regulation of TORC1 signaling / phosphotyrosine residue binding / positive regulation of calcium-mediated signaling / Integrin signaling / FCERI mediated Ca+2 mobilization / SH2 domain binding / regulation of ERK1 and ERK2 cascade / B cell differentiation / FCGR3A-mediated IL10 synthesis / positive regulation of superoxide anion generation / Antigen activates B Cell Receptor (BCR) leading to generation of second messengers / positive regulation of interleukin-8 production / integrin-mediated signaling pathway / Regulation of signaling by CBL / animal organ morphogenesis / FCERI mediated MAPK activation / negative regulation of inflammatory response to antigenic stimulus / FCGR3A-mediated phagocytosis / B cell receptor signaling pathway / non-specific protein-tyrosine kinase / calcium-mediated signaling / non-membrane spanning protein tyrosine kinase activity / positive regulation of protein-containing complex assembly / Inactivation of CSF3 (G-CSF) signaling / receptor internalization / platelet activation / Regulation of actin dynamics for phagocytic cup formation / CLEC7A (Dectin-1) signaling / peptidyl-tyrosine phosphorylation / positive regulation of interleukin-6 production / protein import into nucleus / cellular response to amyloid-beta / positive regulation of peptidyl-tyrosine phosphorylation / 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-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 / 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-2X6 / Tyrosine-protein kinase SYK
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 1.6 Å
AuthorsLee, C.C.
CitationJournal: Bioorg.Med.Chem.Lett. / Year: 2014
Title: Syk inhibitors with high potency in presence of blood.
Authors: Thoma, G. / Blanz, J. / Buhlmayer, P. / Druckes, P. / Kittelmann, M. / Smith, A.B. / van Eis, M. / Vangrevelinghe, E. / Zerwes, H.G. / Che, J.J. / He, X. / Jin, Y. / Lee, C.C. / Michellys, P. ...Authors: Thoma, G. / Blanz, J. / Buhlmayer, P. / Druckes, P. / Kittelmann, M. / Smith, A.B. / van Eis, M. / Vangrevelinghe, E. / Zerwes, H.G. / Che, J.J. / He, X. / Jin, Y. / Lee, C.C. / Michellys, P.Y. / Uno, T. / Liu, H.
History
DepositionMar 21, 2014Deposition site: RCSB / Processing site: RCSB
Revision 1.0Apr 23, 2014Provider: repository / Type: Initial release
Revision 1.1May 21, 2014Group: Database references
Revision 1.2Sep 20, 2023Group: Data collection / Database references ...Data collection / Database references / Derived calculations / Refinement description
Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / database_2 / pdbx_initial_refinement_model / struct_ref_seq_dif / struct_site
Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession ..._database_2.pdbx_DOI / _database_2.pdbx_database_accession / _struct_ref_seq_dif.details / _struct_site.pdbx_auth_asym_id / _struct_site.pdbx_auth_comp_id / _struct_site.pdbx_auth_seq_id

-
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)34,2452
Polymers33,8561
Non-polymers3891
Water4,504250
1


  • Idetical with deposited unit
  • defined by author&software
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
MethodPISA
Unit cell
Length a, b, c (Å)39.889, 85.161, 88.961
Angle α, β, γ (deg.)90.00, 90.00, 90.00
Int Tables number19
Space group name H-MP212121

-
Components

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


Mass: 33855.930 Da / Num. of mol.: 1 / Fragment: Catalytic Domain / Mutation: K467T
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Production host: Spodoptera frugiperda (fall armyworm)
References: UniProt: P43405, non-specific protein-tyrosine kinase
#2: Chemical ChemComp-2X6 / 7-{[(1R,2S)-2-aminocyclohexyl]amino}-5-(1H-indol-7-ylamino)pyrido[4,3-d]pyrimidin-4(3H)-one


Mass: 389.454 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C21H23N7O
#3: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 250 / 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: 2.23 Å3/Da / Density % sol: 44.88 %
Crystal growTemperature: 293 K / Method: vapor diffusion, sitting drop / pH: 6.2
Details: 20% PEG3350, 0.2M ammonium fluoride, pH 6.2, VAPOR DIFFUSION, SITTING DROP, temperature 293K

-
Data collection

DiffractionMean temperature: 200 K
Diffraction sourceSource: SYNCHROTRON / Site: APS / Beamline: 8-BM / Wavelength: 1
DetectorType: ADSC QUANTUM 315 / Detector: CCD
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1 Å / Relative weight: 1
ReflectionResolution: 1.6→85.16 Å / Num. all: 39941 / Num. obs: 240351 / % possible obs: 93.1 % / Biso Wilson estimate: 24.36 Å2 / Rmerge(I) obs: 0.035 / Rsym value: 0.042 / Net I/σ(I): 24.4
Reflection shellResolution: 1.6→1.69 Å / Redundancy: 2.8 % / Rmerge(I) obs: 0.397 / Mean I/σ(I) obs: 2.2 / Rsym value: 0.539 / % possible all: 85.3

-
Processing

Software
NameVersionClassification
REFMACrefinement
BUSTER2.11.2refinement
REFMACphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: pdb entry 1XBA

1xba


Resolution: 1.6→23.37 Å / Cor.coef. Fo:Fc: 0.9574 / Cor.coef. Fo:Fc free: 0.9437 / SU R Cruickshank DPI: 0.079 / Cross valid method: THROUGHOUT / σ(F): 0
RfactorNum. reflection% reflectionSelection details
Rfree0.202 1991 5 %RANDOM
Rwork0.1748 ---
obs0.1761 39834 97.7 %-
all-40771 --
Displacement parametersBiso mean: 29.35 Å2
Baniso -1Baniso -2Baniso -3
1-1.8322 Å20 Å20 Å2
2--2.0994 Å20 Å2
3----3.9316 Å2
Refine analyzeLuzzati coordinate error obs: 0.191 Å
Refinement stepCycle: LAST / Resolution: 1.6→23.37 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms2087 0 29 250 2366
Refine LS restraints
Refine-IDTypeDev idealNumberRestraint functionWeight
X-RAY DIFFRACTIONt_bond_d0.012178HARMONIC2
X-RAY DIFFRACTIONt_angle_deg0.952947HARMONIC2
X-RAY DIFFRACTIONt_dihedral_angle_d755SINUSOIDAL2
X-RAY DIFFRACTIONt_incorr_chiral_ct
X-RAY DIFFRACTIONt_pseud_angle
X-RAY DIFFRACTIONt_trig_c_planes49HARMONIC2
X-RAY DIFFRACTIONt_gen_planes342HARMONIC5
X-RAY DIFFRACTIONt_it2178HARMONIC20
X-RAY DIFFRACTIONt_nbd
X-RAY DIFFRACTIONt_omega_torsion3.39
X-RAY DIFFRACTIONt_other_torsion16.09
X-RAY DIFFRACTIONt_improper_torsion
X-RAY DIFFRACTIONt_chiral_improper_torsion265SEMIHARMONIC5
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_contact2834SEMIHARMONIC4
LS refinement shellResolution: 1.6→1.64 Å / Total num. of bins used: 20
RfactorNum. reflection% reflection
Rfree0.2178 113 4.84 %
Rwork0.2134 2221 -
all0.2136 2334 -
obs--97.7 %
Refinement TLS params.Method: refined / Origin x: 3.7251 Å / Origin y: 11.0332 Å / Origin z: 19.5229 Å
111213212223313233
T-0.0449 Å2-0.0113 Å20.0105 Å2--0.0543 Å20.0032 Å2---0.0613 Å2
L1.5326 °2-0.6807 °2-0.4528 °2-1.4283 °2-0.0245 °2--0.5961 °2
S-0.0232 Å °-0.0928 Å °0.038 Å °-0.0034 Å °0.0319 Å °0.0246 Å °0.0427 Å °0.043 Å °-0.0088 Å °
Refinement TLS groupSelection details: { A|* }

+
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