[English] 日本語
Yorodumi
- PDB-7uy0: Crystal structure of human Fgr tyrosine kinase in complex with A-... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 7uy0
TitleCrystal structure of human Fgr tyrosine kinase in complex with A-419259
Components(Tyrosine-protein kinase ...) x 2
KeywordsTRANSFERASE / Fgr / A-419259 / 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
PHOSPHATE ION / Chem-VSE / Tyrosine-protein kinase Fgr
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.55 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
B: Tyrosine-protein kinase Fgr
hetero molecules


Theoretical massNumber of molelcules
Total (without water)106,13213
Polymers104,5592
Non-polymers1,57311
Water90150
1
A: Tyrosine-protein kinase Fgr
hetero molecules


Theoretical massNumber of molelcules
Total (without water)52,9445
Polymers52,2411
Non-polymers7024
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
2
B: Tyrosine-protein kinase Fgr
hetero molecules


Theoretical massNumber of molelcules
Total (without water)53,1888
Polymers52,3171
Non-polymers8717
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Unit cell
Length a, b, c (Å)49.430, 112.090, 213.730
Angle α, β, γ (deg.)90.000, 90.000, 90.000
Int Tables number19
Space group name H-MP212121

-
Components

-
Tyrosine-protein kinase ... , 2 types, 2 molecules AB

#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: 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: 52317.375 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

-
Non-polymers , 5 types, 61 molecules

#3: Chemical ChemComp-GOL / GLYCEROL / GLYCERIN / PROPANE-1,2,3-TRIOL


Mass: 92.094 Da / Num. of mol.: 3 / Source method: obtained synthetically / Formula: C3H8O3
#4: Chemical ChemComp-VSE / 7-[trans-4-(4-methylpiperazin-1-yl)cyclohexyl]-5-(4-phenoxyphenyl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine


Mass: 482.620 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C29H34N6O / Feature type: SUBJECT OF INVESTIGATION
#5: Chemical
ChemComp-CL / CHLORIDE ION


Mass: 35.453 Da / Num. of mol.: 4 / Source method: obtained synthetically / Formula: Cl
#6: Chemical ChemComp-PO4 / PHOSPHATE ION


Mass: 94.971 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: PO4
#7: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 50 / Source method: isolated from a natural source / Formula: H2O

-
Details

Has ligand of interestY

-
Experimental details

-
Experiment

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

-
Sample preparation

CrystalDensity Matthews: 2.96 Å3/Da / Density % sol: 58.4 %
Crystal growTemperature: 277 K / Method: vapor diffusion / pH: 7.5
Details: For co-crystallization with A-419259, 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 A-419259 (in 50% DMSO) to a final inhibitor concentration of ...Details: For co-crystallization with A-419259, 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 A-419259 (in 50% DMSO) to a final inhibitor concentration of 120 microM (0.3% DMSO final) and incubated for 30 min at 298 K prior to crystallization setup. Crystals were grown by sitting- and hanging-drop vapor diffusion at 277 K by mixing Fgr/A-419259 in a 1:1 ratio with the mother liquor (0.2 M sodium/potassium phosphate, 0.1 M Bis-Tris propane, pH 7.5, and 16% PEG 3350). To promote crystal growth, crystal seeds from initial needle-like crystals were added to the crystallization drops

-
Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: APS / Beamline: 23-ID-D / Wavelength: 1.03326 Å
DetectorType: DECTRIS PILATUS3 6M / Detector: PIXEL / Date: Nov 9, 2018
RadiationMonochromator: Si(111) / Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1.03326 Å / Relative weight: 1
ReflectionResolution: 2.55→77.346 Å / Num. obs: 39772 / % possible obs: 100 % / Redundancy: 12.61 % / Biso Wilson estimate: 65.511 Å2 / CC1/2: 0.998 / Rmerge(I) obs: 0.12 / Rrim(I) all: 0.125 / Χ2: 0.888 / Net I/σ(I): 13.4 / Num. measured all: 501528 / Scaling rejects: 71
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
2.55-2.6212.9091.182.0737657291729170.771.227100
2.62-2.6912.690.9492.5735125276827680.8120.988100
2.69-2.7712.7310.8043.0935506279027890.8710.836100
2.77-2.8512.9340.6353.9634184264326430.9210.661100
2.85-2.9412.8450.4945.1533269259025900.9480.514100
2.94-3.0512.750.3866.3532156252225220.9710.402100
3.05-3.1612.8430.2918.3230747239423940.9820.303100
3.16-3.2912.6180.21710.9329880236823680.9890.226100
3.29-3.4412.5890.17613.3827847221222120.9910.183100
3.44-3.6112.9540.1417.0128200217721770.9940.146100
3.61-3.812.5410.12418.725785205620560.9950.129100
3.8-4.0312.5330.10521.6624100192319230.9960.11100
4.03-4.3112.380.09224.4122668183118310.9970.096100
4.31-4.6612.580.08625.7421764173017300.9970.09100
4.66-5.112.7380.08326.7220342159715970.9970.086100
5.1-5.712.2460.08525.0417622143914390.9970.089100
5.7-6.5811.8130.0826.0215215128812880.9970.083100
6.58-8.0612.3220.0728.613751111611160.9980.073100
8.06-11.411.3410.05831.9299918818810.9980.061100
11.4-77.34610.770.05632.6957195335310.9970.05999.6

-
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: 2.55→77.346 Å / SU ML: 0.33 / Cross valid method: THROUGHOUT / σ(F): 1.35 / Phase error: 22.82 / Stereochemistry target values: ML
RfactorNum. reflection% reflection
Rfree0.2229 2000 5.03 %
Rwork0.1865 37766 -
obs0.1883 39766 99.97 %
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT BULK SOLVENT MODEL
Displacement parametersBiso max: 172.43 Å2 / Biso mean: 71.1545 Å2 / Biso min: 33.05 Å2
Refinement stepCycle: final / Resolution: 2.55→77.346 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms7168 0 104 50 7322
Biso mean--67.04 58.03 -
Num. residues----896
LS refinement shell

Refine-ID: X-RAY DIFFRACTION / Rfactor Rfree error: 0 / % reflection obs: 100 %

Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection Rwork
2.55-2.61380.28641410.25712666
2.6138-2.68450.30291380.24972607
2.6845-2.76350.29251420.24282681
2.7635-2.85270.27811400.26572643
2.8527-2.95460.27861410.25182674
2.9546-3.07290.30011410.2422653
3.0729-3.21280.28411410.2312667
3.2128-3.38220.22851420.21512672
3.3822-3.59410.2891420.20832695
3.5941-3.87160.23321430.18852700
3.8716-4.26120.20491440.15792694
4.2612-4.87770.17311440.14812745
4.8777-6.1450.18721470.172767
6.145-77.3460.19011540.15792902
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)
11.6212-0.0460.56041.7729-1.63551.45810.15750.12970.1209-0.1651-0.22920.21240.2869-0.3247-00.7146-0.039-0.1420.5904-0.0360.564525.2084-8.6172-39.906
21.65750.03521.02342.6449-1.66722.2279-0.09740.0822-0.1301-0.5857-0.0105-0.46290.31660.00940.00010.6627-0.04940.02310.4584-0.00390.515636.7579-30.5842-32.9088
32.49510.02571.16421.83620.4933.0825-0.0097-0.10050.1328-0.0378-0.01260.1304-0.19240.05-0.00010.3375-0.05450.03360.4129-0.03640.407942.12840.563-17.3161
40.74591.2650.34411.85351.10291.93290.1057-0.057-0.29530.30290.1844-0.4520.23740.68640.00010.48320.0664-0.07060.6674-0.03750.593956.8008-14.0266-11.7208
51.07020.66150.60110.88-0.31211.3208-0.01650.16250.35370.23280.10220.7011-0.4802-0.090200.86580.24620.29840.65640.23760.909420.042824.585735.0004
63.03140.39110.18521.13090.53772.97660.25840.0005-0.1590.1538-0.08620.0616-0.0872-0.2473-00.570.08830.14580.55630.09150.615124.45513.854148.6981
70.43910.3640.03510.78380.44071.36810.53710.11740.5394-0.4807-0.3013-0.3893-0.6184-0.19260.00020.69870.14390.17560.52470.16250.932740.459923.528918.0064
81.2818-1.2147-0.82653.3373-0.84711.54070.12290.05540.329-0.01450.0273-0.0779-0.3264-0.16640.00890.54540.06340.09690.53610.07010.53839.72629.856921.3724
90.0162-0.134-0.17050.0174-0.3130.8395-0.01240.2503-0.1673-0.14070.03460.042-0.2847-0.1194-00.64190.00120.06110.70330.0190.555148.2201-0.12775.5991
101.5458-0.95470.68852.20630.05111.976-0.09780.4434-0.1215-0.01270.0224-0.02130.3360.22430.00090.53210.07870.0660.5043-0.01010.510950.791-9.263520.8694
11-0.3004-0.7832-1.8189-0.77080.47930.8768-0.3870.1543-0.2210.10620.09770.27750.5508-0.1509-0.01090.7036-0.03390.16860.6180.00640.645134.0552-10.211932.0067
Refinement TLS group
IDRefine-IDRefine TLS-IDSelection detailsAuth asym-IDAuth seq-ID
1X-RAY DIFFRACTION1chain 'A' and (resid 84 through 154 )A84 - 154
2X-RAY DIFFRACTION2chain 'A' and (resid 155 through 252 )A155 - 252
3X-RAY DIFFRACTION3chain 'A' and (resid 253 through 440 )A253 - 440
4X-RAY DIFFRACTION4chain 'A' and (resid 441 through 531 )A441 - 531
5X-RAY DIFFRACTION5chain 'B' and (resid 84 through 154 )B84 - 154
6X-RAY DIFFRACTION6chain 'B' and (resid 155 through 252 )B155 - 252
7X-RAY DIFFRACTION7chain 'B' and (resid 253 through 286 )B253 - 286
8X-RAY DIFFRACTION8chain 'B' and (resid 287 through 410 )B287 - 410
9X-RAY DIFFRACTION9chain 'B' and (resid 411 through 440 )B411 - 440
10X-RAY DIFFRACTION10chain 'B' and (resid 441 through 498 )B441 - 498
11X-RAY DIFFRACTION11chain 'B' and (resid 499 through 531 )B499 - 531

+
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