[English] 日本語
Yorodumi
- PDB-4c3f: Structure of Lck in complex with a compound discovered by Virtual... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 4c3f
TitleStructure of Lck in complex with a compound discovered by Virtual Fragment Linking
ComponentsTYROSINE-PROTEIN KINASE LCK
KeywordsTRANSFERASE
Function / homology
Function and homology information


regulation of lymphocyte activation / positive regulation of leukocyte cell-cell adhesion / CD27 signaling pathway / Fc-gamma receptor signaling pathway / Co-stimulation by CD28 / FLT3 signaling through SRC family kinases / CD4 receptor binding / Nef Mediated CD4 Down-regulation / intracellular zinc ion homeostasis / Nef and signal transduction ...regulation of lymphocyte activation / positive regulation of leukocyte cell-cell adhesion / CD27 signaling pathway / Fc-gamma receptor signaling pathway / Co-stimulation by CD28 / FLT3 signaling through SRC family kinases / CD4 receptor binding / Nef Mediated CD4 Down-regulation / intracellular zinc ion homeostasis / Nef and signal transduction / positive regulation of heterotypic cell-cell adhesion / Interleukin-2 signaling / CD28 dependent Vav1 pathway / Regulation of KIT signaling / leukocyte migration / phospholipase activator activity / Co-inhibition by CTLA4 / protein serine/threonine phosphatase activity / CD8 receptor binding / pericentriolar material / Translocation of ZAP-70 to Immunological synapse / Phosphorylation of CD3 and TCR zeta chains / positive regulation of T cell receptor signaling pathway / phospholipase binding / PECAM1 interactions / CD28 dependent PI3K/Akt signaling / hemopoiesis / Generation of second messenger molecules / T cell differentiation / RHOH GTPase cycle / immunological synapse / Co-inhibition by PD-1 / phosphatidylinositol 3-kinase binding / T cell receptor binding / peptidyl-tyrosine autophosphorylation / positive regulation of intrinsic apoptotic signaling pathway / GPVI-mediated activation cascade / release of sequestered calcium ion into cytosol / T cell costimulation / phosphotyrosine residue binding / SH2 domain binding / Signaling by phosphorylated juxtamembrane, extracellular and kinase domain KIT mutants / : / T cell activation / B cell receptor signaling pathway / non-membrane spanning protein tyrosine kinase activity / non-specific protein-tyrosine kinase / Signaling by SCF-KIT / peptidyl-tyrosine phosphorylation / platelet activation / positive regulation of T cell activation / cell surface receptor protein tyrosine kinase signaling pathway / Constitutive Signaling by Aberrant PI3K in Cancer / Downstream TCR signaling / PIP3 activates AKT signaling / DAP12 signaling / T cell receptor signaling pathway / ATPase binding / PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling / protein tyrosine kinase activity / protein phosphatase binding / histone H3Y41 kinase activity / histone H2AXY142 kinase activity / intracellular signal transduction / protein phosphorylation / membrane raft / response to xenobiotic stimulus / signaling receptor binding / innate immune response / protein kinase binding / extracellular exosome / ATP binding / identical protein binding / plasma membrane / cytosol / cytoplasm
Similarity search - Function
Lck, SH3 domain / Tyrosine-protein kinase Lck, SH2 domain / : / SH3 domain / SH2 domain / Src homology 2 (SH2) domain profile. / Src homology 2 domains / SH2 domain / Src homology 3 domains / SH2 domain superfamily ...Lck, SH3 domain / Tyrosine-protein kinase Lck, SH2 domain / : / SH3 domain / SH2 domain / Src homology 2 (SH2) domain profile. / Src homology 2 domains / SH2 domain / Src homology 3 domains / SH2 domain superfamily / 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-7KW / Tyrosine-protein kinase Lck
Similarity search - Component
Biological speciesHOMO SAPIENS (human)
MethodX-RAY DIFFRACTION / MOLECULAR REPLACEMENT / Resolution: 1.72 Å
AuthorsCowan-Jacob, S.W. / Rummel, G. / Stark, W.
CitationJournal: J. Med. Chem. / Year: 2013
Title: Efficient search of chemical space: navigating from fragments to structurally diverse chemotypes.
Authors: Wassermann, A.M. / Kutchukian, P.S. / Lounkine, E. / Luethi, T. / Hamon, J. / Bocker, M.T. / Malik, H.A. / Cowan-Jacob, S.W. / Glick, M.
History
DepositionAug 23, 2013Deposition site: PDBE / Processing site: PDBE
Revision 1.0Oct 23, 2013Provider: repository / Type: Initial release
Revision 1.1Jan 15, 2014Group: Database references
Revision 1.2Dec 14, 2016Group: Data collection / Other
Revision 1.3Apr 4, 2018Group: Data collection / Category: diffrn_source / Item: _diffrn_source.type
Revision 1.4Feb 27, 2019Group: Data collection / Database references / Experimental preparation
Category: citation / exptl_crystal_grow ...citation / exptl_crystal_grow / pdbx_database_proc / struct_biol
Item: _citation.journal_abbrev / _citation.journal_id_ISSN ..._citation.journal_abbrev / _citation.journal_id_ISSN / _citation.page_last / _citation.pdbx_database_id_DOI / _citation.title / _exptl_crystal_grow.temp
Revision 1.5Dec 20, 2023Group: Data collection / Database references ...Data collection / Database references / Derived calculations / Other / Refinement description
Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / database_2 / pdbx_database_status / pdbx_initial_refinement_model / struct_site
Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession ..._database_2.pdbx_DOI / _database_2.pdbx_database_accession / _pdbx_database_status.status_code_sf / _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 LCK
hetero molecules


Theoretical massNumber of molelcules
Total (without water)30,9702
Polymers30,6561
Non-polymers3131
Water6,395355
1


  • Idetical with deposited unit
  • defined by author&software
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
MethodPISA
Unit cell
Length a, b, c (Å)58.088, 44.596, 120.254
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 LCK / LEUKOCYTE C-TERMINAL SRC KINASE / LSK / LYMPHOCYTE CELL-SPECIFIC PROTEIN-TYROSINE KINASE / PROTEIN ...LEUKOCYTE C-TERMINAL SRC KINASE / LSK / LYMPHOCYTE CELL-SPECIFIC PROTEIN-TYROSINE KINASE / PROTEIN YT16 / PROTO-ONCOGENE LCK / T CELL-SPECIFIC PROTEIN-TYROSINE KINASE / P56-LCK


Mass: 30656.152 Da / Num. of mol.: 1 / Fragment: KINASE DOMAIN, RESIDUES 237-501 / Mutation: YES
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) HOMO SAPIENS (human) / Production host: SPODOPTERA FRUGIPERDA (fall armyworm)
References: UniProt: P06239, non-specific protein-tyrosine kinase
#2: Chemical ChemComp-7KW / N-phenyl-4-(5-phenyl-1H-pyrazol-4-yl)pyrimidin-2-amine


Mass: 313.356 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C19H15N5
#3: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 355 / 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: 44.49 % / Description: NONE
Crystal growTemperature: 277 K
Details: 16 % PEG 8000, 0.1 M NA CACODYLATE PH 6.5, 0.2 M MG ACETATE, 4 C

-
Data collection

DiffractionMean temperature: 100 K
Diffraction sourceSource: ROTATING ANODE / Type: RIGAKU FR-E / Wavelength: 1.5418
DetectorType: RIGAKU CCD / Detector: CCD / Date: Oct 14, 2005
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1.5418 Å / Relative weight: 1
ReflectionResolution: 1.72→41.81 Å / Num. obs: 30169 / % possible obs: 88.7 % / Observed criterion σ(I): 0 / Redundancy: 6.3 % / Biso Wilson estimate: 27.3 Å2 / Rmerge(I) obs: 0.03 / Net I/σ(I): 32.51
Reflection shellResolution: 1.72→1.77 Å / Redundancy: 2.9 % / Rmerge(I) obs: 0.24 / Mean I/σ(I) obs: 4.38 / % possible all: 46.3

-
Processing

Software
NameVersionClassification
REFMAC5.7.0029refinement
XDSdata reduction
XSCALEdata scaling
REFMACphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: PDB ENTRY 3MPM

3mpm


Resolution: 1.72→41.78 Å / Cor.coef. Fo:Fc: 0.956 / Cor.coef. Fo:Fc free: 0.938 / SU B: 2.316 / SU ML: 0.075 / Cross valid method: THROUGHOUT / ESU R: 0.118 / ESU R Free: 0.118 / Stereochemistry target values: MAXIMUM LIKELIHOOD
Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS. U VALUES REFINED INDIVIDUALLY
RfactorNum. reflection% reflectionSelection details
Rfree0.2196 1508 5 %RANDOM
Rwork0.17741 ---
obs0.17953 28658 88.74 %-
Solvent computationIon probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.2 Å / Solvent model: MASK
Displacement parametersBiso mean: 25.946 Å2
Baniso -1Baniso -2Baniso -3
1--0.4 Å20 Å20 Å2
2--0.19 Å20 Å2
3---0.21 Å2
Refinement stepCycle: LAST / Resolution: 1.72→41.78 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms2078 0 24 355 2457
Refine LS restraints
Refine-IDTypeDev idealDev ideal targetNumber
X-RAY DIFFRACTIONr_bond_refined_d0.0170.0192191
X-RAY DIFFRACTIONr_bond_other_d0.0010.022069
X-RAY DIFFRACTIONr_angle_refined_deg1.6651.9782974
X-RAY DIFFRACTIONr_angle_other_deg0.89834756
X-RAY DIFFRACTIONr_dihedral_angle_1_deg6.1985263
X-RAY DIFFRACTIONr_dihedral_angle_2_deg33.49923.529102
X-RAY DIFFRACTIONr_dihedral_angle_3_deg12.48415380
X-RAY DIFFRACTIONr_dihedral_angle_4_deg20.1131517
X-RAY DIFFRACTIONr_chiral_restr0.1060.2322
X-RAY DIFFRACTIONr_gen_planes_refined0.0080.0212463
X-RAY DIFFRACTIONr_gen_planes_other0.0010.02503
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_it
X-RAY DIFFRACTIONr_mcbond_other
X-RAY DIFFRACTIONr_mcangle_it
X-RAY DIFFRACTIONr_mcangle_other
X-RAY DIFFRACTIONr_scbond_it
X-RAY DIFFRACTIONr_scbond_other
X-RAY DIFFRACTIONr_scangle_it
X-RAY DIFFRACTIONr_scangle_other
X-RAY DIFFRACTIONr_long_range_B_refined
X-RAY DIFFRACTIONr_long_range_B_other
X-RAY DIFFRACTIONr_rigid_bond_restr
X-RAY DIFFRACTIONr_sphericity_free
X-RAY DIFFRACTIONr_sphericity_bonded
LS refinement shellResolution: 1.72→1.765 Å / Total num. of bins used: 20
RfactorNum. reflection% reflection
Rfree0.289 55 -
Rwork0.259 1051 -
obs--44.94 %

+
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