[English] 日本語
Yorodumi
- PDB-3ad6: Crystal structure of Pyrazolo pyrimidine derivative bound to the ... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 3ad6
TitleCrystal structure of Pyrazolo pyrimidine derivative bound to the kinase domain of human LCK, (auto-phosphorylated on TYR394)
ComponentsProto-oncogene tyrosine-protein kinase LCK
KeywordsTRANSFERASE / TYROSINE-PROTEIN KINASE / ATP-BINDING / PHOSPHORYLATION / SIGNAL TRANSDUCTION / KINASE / SH2 DOMAIN / SH3 DOMAIN
Function / homology
Function and homology information


regulation of lymphocyte activation / positive regulation of leukocyte cell-cell adhesion / Fc-gamma receptor signaling pathway / CD28 co-stimulation / FLT3 signaling through SRC family kinases / intracellular zinc ion homeostasis / Nef and signal transduction / CD4 receptor binding / Nef Mediated CD4 Down-regulation / positive regulation of heterotypic cell-cell adhesion ...regulation of lymphocyte activation / positive regulation of leukocyte cell-cell adhesion / Fc-gamma receptor signaling pathway / CD28 co-stimulation / FLT3 signaling through SRC family kinases / intracellular zinc ion homeostasis / Nef and signal transduction / CD4 receptor binding / Nef Mediated CD4 Down-regulation / positive regulation of heterotypic cell-cell adhesion / Interleukin-2 signaling / CD28 dependent Vav1 pathway / Regulation of KIT signaling / leukocyte migration / CTLA4 inhibitory signaling / protein serine/threonine phosphatase activity / phospholipase activator activity / CD8 receptor binding / pericentriolar material / positive regulation of T cell receptor signaling pathway / Translocation of ZAP-70 to Immunological synapse / Phosphorylation of CD3 and TCR zeta chains / PECAM1 interactions / CD28 dependent PI3K/Akt signaling / phospholipase binding / hemopoiesis / RHOH GTPase cycle / Generation of second messenger molecules / immunological synapse / T cell differentiation / PD-1 signaling / phosphatidylinositol 3-kinase binding / positive regulation of intrinsic apoptotic signaling pathway / T cell receptor binding / peptidyl-tyrosine autophosphorylation / cell surface receptor protein tyrosine kinase 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 / non-specific protein-tyrosine kinase / B cell receptor signaling pathway / non-membrane spanning protein tyrosine kinase activity / Signaling by SCF-KIT / : / platelet activation / peptidyl-tyrosine phosphorylation / Constitutive Signaling by Aberrant PI3K in Cancer / positive regulation of T cell activation / 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 / intracellular signal transduction / response to xenobiotic stimulus / protein phosphorylation / membrane raft / innate immune response / signaling receptor binding / protein kinase binding / extracellular exosome / ATP binding / identical protein binding / plasma membrane / cytosol
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 / 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-KSC / Tyrosine-protein kinase Lck
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.15 Å
AuthorsTsuji, E.
CitationJournal: To be Published
Title: Ab initio fragment molecular orbital study of ligand binding to leukocyte-specific protein tyrosine (LCK) kinase
Authors: Ozawa, M. / Ozawa, T. / Tsuji, E. / Okazaki, K. / Takeda, K.
History
DepositionJan 14, 2010Deposition site: PDBJ / Processing site: PDBJ
Revision 1.0Jan 19, 2011Provider: repository / Type: Initial release
Revision 1.1Jul 13, 2011Group: Version format compliance
Revision 1.2Nov 1, 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_conn / struct_site
Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession ..._database_2.pdbx_DOI / _database_2.pdbx_database_accession / _struct_conn.pdbx_leaving_atom_flag / _struct_site.pdbx_auth_asym_id / _struct_site.pdbx_auth_comp_id / _struct_site.pdbx_auth_seq_id
Revision 1.3Nov 15, 2023Group: Data collection / Category: chem_comp_atom / chem_comp_bond / Item: _chem_comp_atom.atom_id / _chem_comp_bond.atom_id_2

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Proto-oncogene tyrosine-protein kinase LCK
hetero molecules


Theoretical massNumber of molelcules
Total (without water)33,7025
Polymers33,0661
Non-polymers6374
Water3,981221
1


  • Idetical with deposited unit
  • defined by author&software
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
MethodPISA
Unit cell
Length a, b, c (Å)42.271, 73.604, 92.344
Angle α, β, γ (deg.)90.00, 90.00, 90.00
Int Tables number19
Space group name H-MP212121

-
Components

#1: Protein Proto-oncogene tyrosine-protein kinase LCK / LYMPHOCYTE KINASE / Lymphocyte cell-specific protein-tyrosine kinase / p56-LCK / LSK / T cell- ...LYMPHOCYTE KINASE / Lymphocyte cell-specific protein-tyrosine kinase / p56-LCK / LSK / T cell-specific protein-tyrosine kinase


Mass: 33065.602 Da / Num. of mol.: 1 / Fragment: RESIDUES 225-509
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: LCK / Plasmid: PET-19B / Cell line (production host): SF9 / Production host: Spodoptera frugiperda (fall armyworm)
References: UniProt: P06239, non-specific protein-tyrosine kinase
#2: Chemical ChemComp-SO4 / SULFATE ION


Mass: 96.063 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: SO4
#3: Chemical ChemComp-DMS / DIMETHYL SULFOXIDE


Mass: 78.133 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C2H6OS / Comment: DMSO, precipitant*YM
#4: Chemical ChemComp-KSC / 7-[(cyclopropylmethyl)amino]-2-[(4-methoxyphenyl)amino]-5-methylpyrazolo[1,5-a]pyrimidine-3-carboxamide


Mass: 366.417 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C19H22N6O2
#5: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 221 / 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: 2.17 Å3/Da / Density % sol: 43.38 %
Crystal growTemperature: 277 K / Method: vapor diffusion, hanging drop / pH: 6.5
Details: 0.2M (NH4)2SO4, 0.1M SODIUM CACODYLATE, 30% PEG 8000, 0.2% MPD, pH 6.5, VAPOR DIFFUSION, HANGING DROP, temperature 277K

-
Data collection

DiffractionMean temperature: 93 K
Diffraction sourceSource: SYNCHROTRON / Site: SPring-8 / Beamline: BL32B2 / Wavelength: 1.5418 Å
DetectorType: RIGAKU JUPITER 210 / Detector: CCD / Date: Oct 23, 2002
RadiationMonochromator: Si 111 CHANNEL / Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1.5418 Å / Relative weight: 1
ReflectionResolution: 2.15→28.71 Å / Num. all: 15875 / Num. obs: 15907 / % possible obs: 98 % / Observed criterion σ(F): 0 / Biso Wilson estimate: 15.3 Å2 / Rmerge(I) obs: 0.13 / Rsym value: 0.155 / Net I/σ(I): 7.3
Reflection shellResolution: 2.15→2.27 Å / Redundancy: 3.2 % / Rmerge(I) obs: 0.251 / Mean I/σ(I) obs: 4.9 / Num. unique all: 2261 / Rsym value: 0.296 / % possible all: 97.5

-
Processing

Software
NameVersionClassification
BSSAT BL32B2data collection
AMoREphasing
REFMAC5.5.0072refinement
MOSFLMdata reduction
SCALAdata scaling
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: PDB ENTRY 3LCK

3lck


Resolution: 2.15→10 Å / Cor.coef. Fo:Fc: 0.917 / Cor.coef. Fo:Fc free: 0.829 / SU B: 5.942 / SU ML: 0.157 / Cross valid method: THROUGHOUT / ESU R: 0.316 / ESU R Free: 0.254 / Stereochemistry target values: MAXIMUM LIKELIHOOD
RfactorNum. reflection% reflectionSelection details
Rfree0.26951 1588 10.1 %RANDOM
Rwork0.18316 ---
obs0.19192 14119 97.63 %-
Solvent computationIon probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.4 Å / Solvent model: MASK
Displacement parametersBiso mean: 5.903 Å2
Baniso -1Baniso -2Baniso -3
1-0.08 Å20 Å20 Å2
2--0.79 Å20 Å2
3----0.87 Å2
Refinement stepCycle: LAST / Resolution: 2.15→10 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms2218 0 41 221 2480
Refine LS restraints
Refine-IDTypeDev idealDev ideal targetNumber
X-RAY DIFFRACTIONr_bond_refined_d0.0140.0222313
X-RAY DIFFRACTIONr_angle_refined_deg1.4641.9823141
X-RAY DIFFRACTIONr_dihedral_angle_1_deg6.0655272
X-RAY DIFFRACTIONr_dihedral_angle_2_deg34.65423.761109
X-RAY DIFFRACTIONr_dihedral_angle_3_deg14.3715395
X-RAY DIFFRACTIONr_dihedral_angle_4_deg15.671517
X-RAY DIFFRACTIONr_chiral_restr0.1050.2335
X-RAY DIFFRACTIONr_gen_planes_refined0.010.0211753
X-RAY DIFFRACTIONr_mcbond_it0.6811.51362
X-RAY DIFFRACTIONr_mcangle_it1.30322204
X-RAY DIFFRACTIONr_scbond_it2.3263951
X-RAY DIFFRACTIONr_scangle_it3.7614.5934
LS refinement shellResolution: 2.15→2.203 Å / Total num. of bins used: 20
RfactorNum. reflection% reflection
Rfree0.274 104 -
Rwork0.188 994 -
obs--97.08 %

+
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