[English] 日本語
Yorodumi
- PDB-7uy3: Crystal structure of human Fgr tyrosine kinase in complex with TL02-59 -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 7uy3
TitleCrystal structure of human Fgr tyrosine kinase in complex with TL02-59
ComponentsTyrosine-protein kinase Fgr
KeywordsTRANSFERASE / Fgr / TL02-59 / SIGNALING PROTEIN / kinase
Function / homology
Function and homology information


immune response-regulating cell surface receptor signaling pathway / negative regulation of natural killer cell activation / positive regulation of mast cell degranulation / Fc-gamma receptor I complex binding / regulation of phagocytosis / aggresome / regulation of protein kinase activity / skeletal system morphogenesis / myoblast proliferation / Platelet sensitization by LDL ...immune response-regulating cell surface receptor signaling pathway / negative regulation of natural killer cell activation / positive regulation of mast cell degranulation / Fc-gamma receptor I complex binding / regulation of phagocytosis / aggresome / regulation of protein kinase activity / skeletal system morphogenesis / myoblast proliferation / Platelet sensitization by LDL / Fc-gamma receptor signaling pathway involved in phagocytosis / regulation of innate immune response / bone mineralization / FCGR activation / negative regulation of inflammatory response to antigenic stimulus / extrinsic component of cytoplasmic side of plasma membrane / immunoglobulin receptor binding / cell surface receptor protein tyrosine kinase signaling pathway / phosphotyrosine residue binding / FCGR3A-mediated IL10 synthesis / positive regulation of cytokine production / integrin-mediated signaling pathway / FCGR3A-mediated phagocytosis / non-specific protein-tyrosine kinase / non-membrane spanning protein tyrosine kinase activity / response to virus / mitochondrial intermembrane space / ruffle membrane / peptidyl-tyrosine phosphorylation / actin cytoskeleton / regulation of cell shape / protein tyrosine kinase activity / secretory granule lumen / protein autophosphorylation / mitochondrial inner membrane / positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction / cell differentiation / defense response to Gram-positive bacterium / positive regulation of cell migration / protein phosphorylation / innate immune response / signaling receptor binding / Neutrophil degranulation / protein kinase binding / extracellular exosome / extracellular region / ATP binding / plasma membrane / cytosol
Similarity search - Function
Tyrosine-protein kinase Fgr, 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. ...Tyrosine-protein kinase Fgr, 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 / Protein tyrosine and serine/threonine kinase / Serine-threonine/tyrosine-protein kinase, catalytic domain / Protein kinase, ATP binding site / Protein kinases ATP-binding region signature. / Protein kinase domain profile. / Protein kinase domain / Protein kinase-like domain superfamily
Similarity search - Domain/homology
Chem-OJL / PHOSPHATE ION / Tyrosine-protein kinase Fgr
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.99 Å
AuthorsDu, S. / Alvarado, J.J. / Smithgall, T.E.
Funding support United States, 1items
OrganizationGrant numberCountry
National Institutes of Health/National Cancer Institute (NIH/NCI)CA233576 United States
CitationJournal: Structure / Year: 2022
Title: ATP-site inhibitors induce unique conformations of the acute myeloid leukemia-associated Src-family kinase, Fgr.
Authors: Du, S. / Alvarado, J.J. / Wales, T.E. / Moroco, J.A. / Engen, J.R. / Smithgall, T.E.
History
DepositionMay 6, 2022Deposition site: RCSB / Processing site: RCSB
Revision 1.0Dec 28, 2022Provider: repository / Type: Initial release
Revision 1.1Oct 25, 2023Group: Data collection / Refinement description
Category: chem_comp_atom / chem_comp_bond / pdbx_initial_refinement_model
Revision 1.2Nov 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: Tyrosine-protein kinase Fgr
hetero molecules


Theoretical massNumber of molelcules
Total (without water)53,1956
Polymers52,2411
Non-polymers9545
Water00
1


  • Idetical with deposited unit
  • defined by author&software
  • Evidence: gel filtration, SEC-MALS
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
MethodPISA
Unit cell
Length a, b, c (Å)151.285, 151.285, 130.518
Angle α, β, γ (deg.)90.000, 90.000, 120.000
Int Tables number179
Space group name H-MP6522

-
Components

#1: Protein Tyrosine-protein kinase Fgr / Gardner-Rasheed feline sarcoma viral (v-fgr) oncogene homolog / Proto-oncogene c-Fgr / p55-Fgr / ...Gardner-Rasheed feline sarcoma viral (v-fgr) oncogene homolog / Proto-oncogene c-Fgr / p55-Fgr / p58-Fgr / p58c-Fgr


Mass: 52241.254 Da / Num. of mol.: 1 / Mutation: Q528E, P529E, G530I, D531P
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: FGR, SRC2 / Plasmid: pFastBac1 / Production host: Spodoptera frugiperda (fall armyworm)
References: UniProt: P09769, non-specific protein-tyrosine kinase
#2: Chemical ChemComp-OJL / 3-[(6,7-dimethoxyquinazolin-4-yl)oxy]-N-{4-[(4-ethylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl}-4-methylbenzamide


Mass: 609.639 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C32H34F3N5O4 / Feature type: SUBJECT OF INVESTIGATION
#3: Chemical ChemComp-EDO / 1,2-ETHANEDIOL / ETHYLENE GLYCOL


Mass: 62.068 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C2H6O2
#4: Chemical ChemComp-GOL / GLYCEROL / GLYCERIN / PROPANE-1,2,3-TRIOL


Mass: 92.094 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C3H8O3
#5: Chemical ChemComp-PO4 / PHOSPHATE ION


Mass: 94.971 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: PO4
Has ligand of interestY

-
Experimental details

-
Experiment

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

-
Sample preparation

CrystalDensity Matthews: 4.2 Å3/Da / Density % sol: 70.7 %
Crystal growTemperature: 277 K / Method: vapor diffusion / pH: 7.5
Details: For co-crystallization with TL02-59, Fgr (3.2 mg/mL in 20 mM Tris-HCl, pH 8.3, 100 mM NaCl, and 2 mM TCEP) was mixed with 10 mM TL02-59 (in 100% DMSO) to a final concentration of 120 microM ...Details: For co-crystallization with TL02-59, Fgr (3.2 mg/mL in 20 mM Tris-HCl, pH 8.3, 100 mM NaCl, and 2 mM TCEP) was mixed with 10 mM TL02-59 (in 100% DMSO) to a final concentration of 120 microM (0.6% DMSO final) and incubated for thirty minutes at 298 K. Diffraction quality crystals were grown by sitting- and hanging-drop vapor diffusion at 277 K by mixing Fgr/TL02-59 in a 1:1 ratio with the mother liquor (0.1 M HEPES, pH 7.5, 0.8 M sodium phosphate, 0.8 M potassium phosphate and 1% 1,2-butanediol)

-
Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: APS / Beamline: 22-ID / Wavelength: 0.9757 Å
DetectorType: DECTRIS EIGER X 16M / Detector: PIXEL / Date: Mar 29, 2018
RadiationMonochromator: Si(111) / Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.9757 Å / Relative weight: 1
ReflectionResolution: 2.99→46.233 Å / Num. obs: 33705 / % possible obs: 99.9 % / Redundancy: 10.954 % / Biso Wilson estimate: 84.007 Å2 / CC1/2: 0.997 / Rmerge(I) obs: 0.125 / Rrim(I) all: 0.131 / Χ2: 0.905 / Net I/σ(I): 11.89
Reflection shell

Diffraction-ID: 1

Resolution (Å)Redundancy (%)Rmerge(I) obsMean I/σ(I) obsNum. measured obsNum. possibleNum. unique obsCC1/2Rrim(I) all% possible all
2.99-3.0711.230.8042.0714722131313110.9090.8499.8
3.07-3.1510.9520.6092.7814271130513030.9310.63799.8
3.15-3.2410.2270.5013.6212712124412430.9560.52699.9
3.24-3.3410.9140.3774.7513435123112310.9780.395100
3.34-3.4511.6450.2846.6713916119611950.9870.29699.9
3.45-3.5711.7530.2238.113492114811480.9920.232100
3.57-3.7111.5740.1929.6512917111711160.9930.299.9
3.71-3.8611.4220.16411.4712279107610750.9950.1799.9
3.86-4.0311.3310.14513.6411637102810270.9940.1599.9
4.03-4.2311.0780.12915.03110569989980.9950.134100
4.23-4.4610.7480.11317.3101789479470.9960.117100
4.46-4.7310.0880.10717.590498998970.9960.11299.8
4.73-5.0510.370.10318.7288258518510.9960.108100
5.05-5.4611.4720.10419.6990867927920.9960.107100
5.46-5.9811.2490.10319.7383477427420.9960.107100
5.98-6.6911.0240.120.3673426676660.9950.10499.9
6.69-7.7210.5670.09221.5464676126120.9950.097100
7.72-9.469.1430.08422.0847455195190.9950.089100
9.46-13.3710.1110.0824.0841964154150.9980.084100
13.37-46.2338.8040.07921.9722012612500.9960.08495.8

-
Processing

Software
NameVersionClassification
PHENIX1.14_3260refinement
XDSdata reduction
XSCALEdata scaling
PDB_EXTRACT3.27data extraction
PHASERphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 2SRC

2src


Resolution: 2.99→46.233 Å / SU ML: 0.41 / Cross valid method: THROUGHOUT / σ(F): 1.36 / Phase error: 26.18 / Stereochemistry target values: ML
RfactorNum. reflection% reflection
Rfree0.2473 3368 9.99 %
Rwork0.2031 30337 -
obs0.2074 33705 99.67 %
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT BULK SOLVENT MODEL
Displacement parametersBiso max: 232.45 Å2 / Biso mean: 104.6638 Å2 / Biso min: 53.78 Å2
Refinement stepCycle: final / Resolution: 2.99→46.233 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms3069 0 64 0 3133
Biso mean--101.46 --
Num. residues----386
LS refinement shell

Refine-ID: X-RAY DIFFRACTION / Rfactor Rfree error: 0

Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection Rwork% reflection obs (%)
2.99-3.03220.37071420.3196125999
3.0322-3.07750.42571420.3466126699
3.0775-3.12560.37761370.3259124799
3.1256-3.17680.31291470.30131266100
3.1768-3.23160.27781300.26931263100
3.2316-3.29030.30351440.25751274100
3.2903-3.35360.29441400.25651252100
3.3536-3.4220.29051370.2505126599
3.422-3.49640.2881380.24511267100
3.4964-3.57770.26961450.24071257100
3.5777-3.66710.27731340.23371263100
3.6671-3.76620.22911400.19591266100
3.7662-3.8770.23931440.18341267100
3.877-4.00210.20131410.16461273100
4.0021-4.1450.21871410.17981245100
4.145-4.31090.2111420.17241275100
4.3109-4.50690.22361430.16481271100
4.5069-4.74430.21661330.15961269100
4.7443-5.04120.21981390.16691278100
5.0412-5.42990.23031430.17571258100
5.4299-5.97530.23671410.19981266100
5.9753-6.83750.23651410.20851269100
6.8375-8.60550.2281470.1931268100
8.6055-46.230.27611370.2172125399
Refinement TLS params.

Method: refined / Refine-ID: X-RAY DIFFRACTION

IDL11 (°2)L12 (°2)L13 (°2)L22 (°2)L23 (°2)L33 (°2)S11 (Å °)S12 (Å °)S13 (Å °)S21 (Å °)S22 (Å °)S23 (Å °)S31 (Å °)S32 (Å °)S33 (Å °)T11 (Å2)T12 (Å2)T13 (Å2)T22 (Å2)T23 (Å2)T33 (Å2)Origin x (Å)Origin y (Å)Origin z (Å)
12.5096-0.9345-1.34571.4469-1.17363.00280.2222-0.29220.10890.1675-0.0870.1066-0.00090.018-0.00030.86670.09440.0270.7899-0.02320.6982-66.8818-24.043518.3405
20.3407-0.48750.1860.5851-0.21920.06580.4218-0.1505-0.122-0.3962-0.2938-0.0685-0.1098-0.5503-0.01861.2270.1038-0.09680.72170.05990.9387-59.1205-44.451921.1515
32.8692-0.6873-1.75082.28180.13481.1705-0.4078-0.69970.07690.31410.29810.0277-0.08940.40020.00010.81930.19390.04670.65660.00360.6663-39.3266-43.31433.178
41.55771.2888-0.53143.0543-1.41031.7878-0.08660.0481-0.015-0.2883-0.1605-0.33220.23050.5436-0.30120.63720.28480.02740.7951-0.04310.7125-51.8959-16.72125.6669
Refinement TLS group
IDRefine-IDRefine TLS-IDSelection detailsAuth asym-IDAuth seq-ID
1X-RAY DIFFRACTION1chain 'A' and (resid 380 through 499 )A380 - 499
2X-RAY DIFFRACTION2chain 'A' and (resid 500 through 531 )A500 - 531
3X-RAY DIFFRACTION3chain 'A' and (resid 139 through 251 )A139 - 251
4X-RAY DIFFRACTION4chain 'A' and (resid 252 through 379 )A252 - 379

+
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://pdbjlvh1.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