[English] 日本語
Yorodumi
- PDB-6yr9: FOCAL ADHESION KINASE CATALYTIC DOMAIN IN COMPLEX WITH N-Methyl-N... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 6yr9
TitleFOCAL ADHESION KINASE CATALYTIC DOMAIN IN COMPLEX WITH N-Methyl-N-(2-{[2-(2-oxo-2,3-dihydro-1H-indol-5-ylamino)-5-trifluoromethyl-pyrimidin-4-ylamino]-methyl}-phenyl)-methanesulfonamide
ComponentsFocal adhesion kinase 1
KeywordsTRANSFERASE / PROTEIN TYROSINE KINASE / ATP BINDING / TRANSFERASE-INHIBITOR COMPLEX
Function / homology
Function and homology information


netrin-activated signaling pathway / regulation of substrate adhesion-dependent cell spreading / regulation of endothelial cell migration / regulation of epithelial cell migration / detection of muscle stretch / positive regulation of ubiquitin-dependent protein catabolic process / JUN kinase binding / signal complex assembly / positive regulation of fibroblast migration / positive regulation of macrophage proliferation ...netrin-activated signaling pathway / regulation of substrate adhesion-dependent cell spreading / regulation of endothelial cell migration / regulation of epithelial cell migration / detection of muscle stretch / positive regulation of ubiquitin-dependent protein catabolic process / JUN kinase binding / signal complex assembly / positive regulation of fibroblast migration / positive regulation of macrophage proliferation / DCC mediated attractive signaling / regulation of osteoblast differentiation / growth hormone receptor signaling pathway / Signal regulatory protein family interactions / MET activates PTK2 signaling / Fc-gamma receptor signaling pathway involved in phagocytosis / regulation of focal adhesion assembly / regulation of GTPase activity / positive regulation of wound healing / establishment of cell polarity / p130Cas linkage to MAPK signaling for integrins / negative regulation of cell-cell adhesion / positive regulation of macrophage chemotaxis / positive regulation of epithelial cell migration / Apoptotic cleavage of cellular proteins / regulation of cytoskeleton organization / regulation of cell adhesion mediated by integrin / GRB2:SOS provides linkage to MAPK signaling for Integrins / negative regulation of anoikis / ephrin receptor signaling pathway / positive regulation of protein kinase activity / Estrogen-dependent nuclear events downstream of ESR-membrane signaling / RHO GTPases Activate WASPs and WAVEs / regulation of cell adhesion / vascular endothelial growth factor receptor signaling pathway / heart morphogenesis / positive regulation of epithelial to mesenchymal transition / stress fiber / EPHB-mediated forward signaling / Integrin signaling / NCAM signaling for neurite out-growth / SH2 domain binding / transforming growth factor beta receptor signaling pathway / ciliary basal body / protein tyrosine phosphatase activity / axon guidance / molecular function activator activity / integrin-mediated signaling pathway / cell motility / non-specific protein-tyrosine kinase / FCGR3A-mediated phagocytosis / non-membrane spanning protein tyrosine kinase activity / regulation of protein phosphorylation / epidermal growth factor receptor signaling pathway / placenta development / Regulation of actin dynamics for phagocytic cup formation / VEGFA-VEGFR2 Pathway / peptidyl-tyrosine phosphorylation / integrin binding / cell migration / regulation of cell shape / regulation of cell population proliferation / actin binding / cell cortex / RAF/MAP kinase cascade / protein tyrosine kinase activity / protein phosphatase binding / angiogenesis / protein autophosphorylation / Extra-nuclear estrogen signaling / dendritic spine / positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction / cytoskeleton / positive regulation of cell migration / positive regulation of protein phosphorylation / intracellular membrane-bounded organelle / focal adhesion / centrosome / positive regulation of cell population proliferation / negative regulation of apoptotic process / protein kinase binding / perinuclear region of cytoplasm / ATP binding / nucleus / plasma membrane / cytosol / cytoplasm
Similarity search - Function
Focal adhesion kinase, targeting (FAT) domain / Focal adhesion kinase, targeting (FAT) domain superfamily / Focal adhesion kinase, N-terminal / FAK1/PYK2, FERM domain C-lobe / Focal adhesion targeting region / FERM N-terminal domain / : / FAK1/PYK2, FERM domain C-lobe / FERM domain signature 2. / FERM central domain ...Focal adhesion kinase, targeting (FAT) domain / Focal adhesion kinase, targeting (FAT) domain superfamily / Focal adhesion kinase, N-terminal / FAK1/PYK2, FERM domain C-lobe / Focal adhesion targeting region / FERM N-terminal domain / : / FAK1/PYK2, FERM domain C-lobe / FERM domain signature 2. / FERM central domain / FERM/acyl-CoA-binding protein superfamily / FERM central domain / FERM superfamily, second domain / FERM domain / FERM domain profile. / Band 4.1 domain / Band 4.1 homologues / Tyrosine-protein kinase, catalytic domain / Tyrosine kinase, catalytic domain / Tyrosine protein kinases specific active-site signature. / Tyrosine-protein kinase, active site / PH-like domain superfamily / Serine-threonine/tyrosine-protein kinase, catalytic domain / Protein tyrosine and serine/threonine kinase / Ubiquitin-like domain superfamily / 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-P9K / Focal adhesion kinase 1
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 1.925 Å
AuthorsMusil, D. / Amaral, M.
CitationJournal: Cell Chem Biol / Year: 2021
Title: Structure-kinetic relationship reveals the mechanism of selectivity of FAK inhibitors over PYK2.
Authors: Berger, B.T. / Amaral, M. / Kokh, D.B. / Nunes-Alves, A. / Musil, D. / Heinrich, T. / Schroder, M. / Neil, R. / Wang, J. / Navratilova, I. / Bomke, J. / Elkins, J.M. / Muller, S. / Frech, M. ...Authors: Berger, B.T. / Amaral, M. / Kokh, D.B. / Nunes-Alves, A. / Musil, D. / Heinrich, T. / Schroder, M. / Neil, R. / Wang, J. / Navratilova, I. / Bomke, J. / Elkins, J.M. / Muller, S. / Frech, M. / Wade, R.C. / Knapp, S.
History
DepositionApr 19, 2020Deposition site: PDBE / Processing site: PDBE
Revision 1.0Feb 10, 2021Provider: repository / Type: Initial release
Revision 1.1Jun 2, 2021Group: Database references / Category: citation / Item: _citation.journal_volume / _citation.page_first
Revision 1.2Jan 24, 2024Group: Data collection / Database references / Refinement description
Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / database_2 / pdbx_initial_refinement_model
Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Focal adhesion kinase 1
B: Focal adhesion kinase 1
C: Focal adhesion kinase 1
D: Focal adhesion kinase 1
hetero molecules


Theoretical massNumber of molelcules
Total (without water)131,2358
Polymers129,2174
Non-polymers2,0184
Water3,153175
1
A: Focal adhesion kinase 1
hetero molecules


Theoretical massNumber of molelcules
Total (without water)32,8092
Polymers32,3041
Non-polymers5041
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
2
B: Focal adhesion kinase 1
hetero molecules


Theoretical massNumber of molelcules
Total (without water)32,8092
Polymers32,3041
Non-polymers5041
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
3
C: Focal adhesion kinase 1
hetero molecules


Theoretical massNumber of molelcules
Total (without water)32,8092
Polymers32,3041
Non-polymers5041
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
4
D: Focal adhesion kinase 1
hetero molecules


Theoretical massNumber of molelcules
Total (without water)32,8092
Polymers32,3041
Non-polymers5041
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Unit cell
Length a, b, c (Å)110.222, 74.538, 172.546
Angle α, β, γ (deg.)90.000, 103.110, 90.000
Int Tables number5
Space group name H-MC121

-
Components

#1: Protein
Focal adhesion kinase 1 / FADK 1 / Focal adhesion kinase-related nonkinase / FRNK / Protein phosphatase 1 regulatory subunit ...FADK 1 / Focal adhesion kinase-related nonkinase / FRNK / Protein phosphatase 1 regulatory subunit 71 / PPP1R71 / Protein-tyrosine kinase 2 / p125FAK / pp125FAK


Mass: 32304.221 Da / Num. of mol.: 4
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: PTK2, FAK, FAK1 / Production host: Trichoplusia ni (cabbage looper)
References: UniProt: Q05397, non-specific protein-tyrosine kinase
#2: Chemical
ChemComp-P9K / N-Methyl-N-(2-{[2-(2-oxo-2,3-dihydro-1H-indol-5-ylamino)-5-trifluoromethyl-pyrimidin-4-ylamino]-methyl}-phenyl)-methanesulfonamide


Mass: 504.485 Da / Num. of mol.: 4 / Source method: obtained synthetically / Formula: C22H19F3N6O3S / Feature type: SUBJECT OF INVESTIGATION
#3: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 175 / Source method: isolated from a natural source / Formula: H2O
Has ligand of interestY

-
Experimental details

-
Experiment

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

-
Sample preparation

CrystalDensity Matthews: 2.67 Å3/Da / Density % sol: 53.95 %
Crystal growTemperature: 294 K / Method: vapor diffusion, hanging drop / pH: 7.5 / Details: 15% PEG 3350, 0.2 M Na acetate

-
Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: SLS / Beamline: X06SA / Wavelength: 0.99993 Å
DetectorType: PSI PILATUS 6M / Detector: PIXEL / Date: Oct 13, 2016
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.99993 Å / Relative weight: 1
ReflectionResolution: 1.925→84.03 Å / Num. obs: 48069 / % possible obs: 88 % / Redundancy: 3.4 % / CC1/2: 0.999 / Rpim(I) all: 0.045 / Rrim(I) all: 0.063 / Net I/σ(I): 14.3
Reflection shellResolution: 1.925→2.168 Å / Num. unique obs: 2402 / CC1/2: 0.67 / Rrim(I) all: 0.771

-
Processing

Software
NameVersionClassification
BUSTER2.11.7 (19-MAR-2020)refinement
PDB_EXTRACT3.25data extraction
XDSdata reduction
XSCALEdata scaling
PHASERphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 4GU6

4gu6


Resolution: 1.925→84.03 Å / Cor.coef. Fo:Fc: 0.909 / Cor.coef. Fo:Fc free: 0.899 / SU R Cruickshank DPI: 0.386 / Cross valid method: THROUGHOUT / σ(F): 0 / SU R Blow DPI: 0.365 / SU Rfree Blow DPI: 0.224 / SU Rfree Cruickshank DPI: 0.23
RfactorNum. reflection% reflectionSelection details
Rfree0.2183 2368 4.93 %RANDOM
Rwork0.1917 ---
obs0.193 48069 46.5 %-
Displacement parametersBiso max: 104.33 Å2 / Biso mean: 38.36 Å2 / Biso min: 7.81 Å2
Baniso -1Baniso -2Baniso -3
1-10.1168 Å20 Å27.408 Å2
2---0.9026 Å20 Å2
3----9.2141 Å2
Refine analyzeLuzzati coordinate error obs: 0.3 Å
Refinement stepCycle: final / Resolution: 1.925→84.03 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms8349 0 210 175 8734
Biso mean--22.93 25.63 -
Num. residues----1038
Refine LS restraints
Refine-IDTypeNumberRestraint functionWeightDev ideal
X-RAY DIFFRACTIONt_dihedral_angle_d3101SINUSOIDAL2
X-RAY DIFFRACTIONt_trig_c_planes
X-RAY DIFFRACTIONt_gen_planes1591HARMONIC5
X-RAY DIFFRACTIONt_it8767HARMONIC10
X-RAY DIFFRACTIONt_nbd
X-RAY DIFFRACTIONt_improper_torsion
X-RAY DIFFRACTIONt_pseud_angle
X-RAY DIFFRACTIONt_chiral_improper_torsion1099SEMIHARMONIC5
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_contact6587SEMIHARMONIC4
X-RAY DIFFRACTIONt_bond_d8767HARMONIC20.008
X-RAY DIFFRACTIONt_angle_deg11889HARMONIC20.86
X-RAY DIFFRACTIONt_omega_torsion3.13
X-RAY DIFFRACTIONt_other_torsion17.04
LS refinement shellResolution: 1.93→2.09 Å / Rfactor Rfree error: 0 / Total num. of bins used: 51
RfactorNum. reflection% reflection
Rfree0.2836 50 5.2 %
Rwork0.2277 912 -
all0.2306 962 -
obs--4.32 %
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)
11.01490.0917-1.94851.7272-0.75765.3478-0.12090.053-0.10980.1068-0.03770.0622-0.05950.0880.15860.0230.04560.0831-0.06940.0172-0.194418.9544-9.886341.412
20.65210.3947-1.29081.3148-0.4943.68140.03460.057-0.03410.1503-0.1177-0.11160.0437-0.0790.08310.0967-0.04840.0813-0.1114-0.0279-0.150825.2388-38.56637.3445
30.35220.2925-0.55511.96850.98874.0499-0.042-0.03640.0275-0.00090.0451-0.07280.1160.2288-0.00320.1490.01950.1067-0.0951-0.0141-0.24318.0444-57.928376.5066
42.36020.2016-0.25120.612-0.33053.74660.0903-0.157-0.3230.0670.1549-0.0107-0.2445-0.2461-0.24520.0270.06620.087-0.13240.0825-0.110352.8219-24.318832.4993
Refinement TLS group
IDRefine-IDRefine TLS-IDSelection detailsAuth asym-IDAuth seq-ID
1X-RAY DIFFRACTION1{ A|* }A415 - 686
2X-RAY DIFFRACTION2{ B|* }B414 - 684
3X-RAY DIFFRACTION3{ C|* }C414 - 686
4X-RAY DIFFRACTION4{ D|* }D412 - 685

+
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