[English] 日本語
Yorodumi
- PDB-7pi4: FAK Protac GSK215 in complex with FAK and pVHL:ElonginC:ElonginB -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 7pi4
TitleFAK Protac GSK215 in complex with FAK and pVHL:ElonginC:ElonginB
Components
  • Elongin-B
  • Focal adhesion kinase 1
  • Isoform 2 of Elongin-C
  • von Hippel-Lindau disease tumor suppressor
KeywordsTRANSFERASE / PROTAC
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 / regulation of cellular response to hypoxia / RHOBTB3 ATPase cycle / negative regulation of receptor signaling pathway via JAK-STAT / JUN kinase binding / transcription elongation factor activity ...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 / regulation of cellular response to hypoxia / RHOBTB3 ATPase cycle / negative regulation of receptor signaling pathway via JAK-STAT / JUN kinase binding / transcription elongation factor activity / target-directed miRNA degradation / signal complex assembly / elongin complex / positive regulation of ubiquitin-dependent protein catabolic process / positive regulation of macrophage proliferation / DCC mediated attractive signaling / Replication of the SARS-CoV-1 genome / Signal regulatory protein family interactions / positive regulation of fibroblast migration / regulation of GTPase activity / VCB complex / MET activates PTK2 signaling / growth hormone receptor signaling pathway / regulation of focal adhesion assembly / Cul5-RING ubiquitin ligase complex / negative regulation of cell-cell adhesion / intracellular membraneless organelle / Cul2-RING ubiquitin ligase complex / positive regulation of wound healing / p130Cas linkage to MAPK signaling for integrins / Apoptotic cleavage of cellular proteins / regulation of osteoblast differentiation / SUMOylation of ubiquitinylation proteins / regulation of cytoskeleton organization / regulation of cell adhesion mediated by integrin / positive regulation of macrophage chemotaxis / Fc-gamma receptor signaling pathway involved in phagocytosis / establishment of cell polarity / regulation of protein phosphorylation / vascular endothelial cell response to oscillatory fluid shear stress / GRB2:SOS provides linkage to MAPK signaling for Integrins / positive regulation of protein kinase activity / negative regulation of anoikis / negative regulation of transcription elongation by RNA polymerase II / Pausing and recovery of Tat-mediated HIV elongation / Tat-mediated HIV elongation arrest and recovery / positive regulation of epithelial cell migration / HIV elongation arrest and recovery / Pausing and recovery of HIV elongation / Estrogen-dependent nuclear events downstream of ESR-membrane signaling / RHO GTPases Activate WASPs and WAVEs / vascular endothelial growth factor receptor signaling pathway / ephrin receptor signaling pathway / negative regulation of signal transduction / positive regulation of epithelial to mesenchymal transition / Tat-mediated elongation of the HIV-1 transcript / regulation of cell adhesion / Formation of HIV-1 elongation complex containing HIV-1 Tat / heart morphogenesis / ubiquitin-like ligase-substrate adaptor activity / Formation of HIV elongation complex in the absence of HIV Tat / RNA Polymerase II Transcription Elongation / stress fiber / Formation of RNA Pol II elongation complex / negative regulation of TORC1 signaling / Integrin signaling / EPHB-mediated forward signaling / RNA Polymerase II Pre-transcription Events / NCAM signaling for neurite out-growth / transforming growth factor beta receptor signaling pathway / negative regulation of autophagy / protein tyrosine phosphatase activity / axon guidance / protein serine/threonine kinase binding / SH2 domain binding / molecular function activator activity / peptidyl-tyrosine phosphorylation / Turbulent (oscillatory, disturbed) flow shear stress activates signaling by PIEZO1 and integrins in endothelial cells / placenta development / transcription corepressor binding / integrin-mediated signaling pathway / non-membrane spanning protein tyrosine kinase activity / FCGR3A-mediated phagocytosis / TP53 Regulates Transcription of DNA Repair Genes / non-specific protein-tyrosine kinase / positive regulation of cell differentiation / transcription initiation at RNA polymerase II promoter / transcription elongation by RNA polymerase II / cell motility / Vif-mediated degradation of APOBEC3G / Inactivation of CSF3 (G-CSF) signaling / Regulation of actin dynamics for phagocytic cup formation / Oxygen-dependent proline hydroxylation of Hypoxia-inducible Factor Alpha / Evasion by RSV of host interferon responses / VEGFA-VEGFR2 Pathway / integrin binding / epidermal growth factor receptor signaling pathway / Regulation of expression of SLITs and ROBOs / cell morphogenesis / positive regulation of protein phosphorylation
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 / von Hippel-Lindau disease tumour suppressor, beta/alpha domain / von Hippel-Lindau disease tumour suppressor, alpha 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 / von Hippel-Lindau disease tumour suppressor, beta/alpha domain / von Hippel-Lindau disease tumour suppressor, alpha domain / von Hippel-Lindau disease tumour suppressor, beta domain / VHL superfamily / von Hippel-Lindau disease tumour suppressor, alpha domain superfamily / von Hippel-Lindau disease tumour suppressor, beta domain superfamily / VHL beta domain / VHL box domain / FERM domain signature 2. / Elongin B / 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 / Ubiquitin family / Tyrosine-protein kinase, catalytic domain / Tyrosine kinase, catalytic domain / Tyrosine protein kinases specific active-site signature. / Ubiquitin homologues / PH-like domain superfamily / Tyrosine-protein kinase, active site / Ubiquitin domain profile. / Ubiquitin-like domain / 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-7QB / DI(HYDROXYETHYL)ETHER / von Hippel-Lindau disease tumor suppressor / Focal adhesion kinase 1 / Isoform 2 of Elongin-C / Elongin-B
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.24 Å
AuthorsChung, C.
Funding support1items
OrganizationGrant numberCountry
Not funded
CitationJournal: Angew.Chem.Int.Ed.Engl. / Year: 2021
Title: Discovery and Characterisation of Highly Cooperative FAK-Degrading PROTACs.
Authors: Law, R.P. / Nunes, J. / Chung, C.W. / Bantscheff, M. / Buda, K. / Dai, H. / Evans, J.P. / Flinders, A. / Klimaszewska, D. / Lewis, A.J. / Muelbaier, M. / Scott-Stevens, P. / Stacey, P. / ...Authors: Law, R.P. / Nunes, J. / Chung, C.W. / Bantscheff, M. / Buda, K. / Dai, H. / Evans, J.P. / Flinders, A. / Klimaszewska, D. / Lewis, A.J. / Muelbaier, M. / Scott-Stevens, P. / Stacey, P. / Tame, C.J. / Watt, G.F. / Zinn, N. / Queisser, M.A. / Harling, J.D. / Benowitz, A.B.
History
DepositionAug 19, 2021Deposition site: PDBE / Processing site: PDBE
Revision 1.0Sep 29, 2021Provider: repository / Type: Initial release
Revision 1.1Oct 20, 2021Group: Data collection / Database references / Category: citation / citation_author / pdbx_database_proc
Item: _citation.journal_volume / _citation.page_first ..._citation.journal_volume / _citation.page_first / _citation.page_last / _citation_author.identifier_ORCID
Revision 1.2Jan 31, 2024Group: Data collection / Derived calculations / Refinement description
Category: atom_type / chem_comp_atom ...atom_type / chem_comp_atom / chem_comp_bond / pdbx_initial_refinement_model
Item: _atom_type.pdbx_N_electrons / _atom_type.pdbx_scat_Z

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
AAA: von Hippel-Lindau disease tumor suppressor
BBB: Elongin-B
CCC: Isoform 2 of Elongin-C
DDD: Focal adhesion kinase 1
hetero molecules


Theoretical massNumber of molelcules
Total (without water)74,40424
Polymers72,0864
Non-polymers2,31920
Water2,702150
1


  • Idetical with deposited unit
  • defined by author
  • Evidence: gel filtration
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area10680 Å2
ΔGint8 kcal/mol
Surface area29820 Å2
Unit cell
Length a, b, c (Å)59.550, 77.260, 175.180
Angle α, β, γ (deg.)90.000, 90.000, 90.000
Int Tables number19
Space group name H-MP212121

-
Components

-
Protein , 4 types, 4 molecules AAABBBCCCDDD

#1: Protein von Hippel-Lindau disease tumor suppressor / Protein G7 / pVHL


Mass: 18012.527 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: VHL / Production host: Escherichia coli BL21(DE3) (bacteria) / References: UniProt: P40337
#2: Protein Elongin-B / EloB / Elongin 18 kDa subunit / RNA polymerase II transcription factor SIII subunit B / SIII p18 / ...EloB / Elongin 18 kDa subunit / RNA polymerase II transcription factor SIII subunit B / SIII p18 / Transcription elongation factor B polypeptide 2


Mass: 11845.521 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: ELOB, TCEB2 / Production host: Escherichia coli BL21(DE3) (bacteria) / References: UniProt: Q15370
#3: Protein Isoform 2 of Elongin-C / EloC / Elongin 15 kDa subunit / RNA polymerase II transcription factor SIII subunit C / SIII p15 / ...EloC / Elongin 15 kDa subunit / RNA polymerase II transcription factor SIII subunit C / SIII p15 / Transcription elongation factor B polypeptide 1


Mass: 10843.420 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: ELOC, TCEB1 / Production host: Escherichia coli BL21(DE3) (bacteria) / References: UniProt: Q15369-2
#4: 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: 31384.350 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: PTK2, FAK, FAK1 / Production host: Spodoptera frugiperda (fall armyworm)
References: UniProt: Q05397, non-specific protein-tyrosine kinase

-
Non-polymers , 5 types, 170 molecules

#5: Chemical ChemComp-7QB / (2S,4R)-4-hydroxy-1-((S)-2-(2-(4-(3-methoxy-4-((4-((2-(methylcarbamoyl)phenyl)amino)-5-(trifluoromethyl)pyridin-2-yl)amino)phenyl)piperazin-1-yl)acetamido)-3,3-dimethylbutanoyl)-N-((S)-1-(4-(4-methylthiazol-5-yl)phenyl)ethyl)pyrrolidine-2-carboxamide / (2S,4R)-1-[(2S)-2-[2-[4-[3-methoxy-4-[[4-[[2-(methylcarbamoyl)phenyl]amino]-5-(trifluoromethyl)pyridin-2-yl]amino]phenyl]piperazin-1-yl]ethanoylamino]-3,3-dimethyl-butanoyl]-N-[(1S)-1-[4-(4-methyl-1,3-thiazol-5-yl)phenyl]ethyl]-4-oxidanyl-pyrrolidine-2-carboxamide


Mass: 985.127 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C50H59F3N10O6S / Feature type: SUBJECT OF INVESTIGATION
#6: Chemical
ChemComp-PEG / DI(HYDROXYETHYL)ETHER


Mass: 106.120 Da / Num. of mol.: 4 / Source method: obtained synthetically / Formula: C4H10O3
#7: Chemical
ChemComp-EDO / 1,2-ETHANEDIOL / ETHYLENE GLYCOL


Mass: 62.068 Da / Num. of mol.: 14 / Source method: obtained synthetically / Formula: C2H6O2
#8: Chemical ChemComp-CA / CALCIUM ION


Mass: 40.078 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: Ca
#9: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 150 / 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: 2.87 Å3/Da / Density % sol: 57.1 %
Crystal growTemperature: 293 K / Method: vapor diffusion / Details: 0.05M CaCl, 0.1M MES pH 6.5, 45%v/v, PEG200

-
Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: SSRF / Beamline: BL17U1 / Wavelength: 0.97918 Å
DetectorType: DECTRIS EIGER2 X 16M / Detector: PIXEL / Date: Jun 11, 2018
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.97918 Å / Relative weight: 1
ReflectionResolution: 2.24→58.39 Å / Num. obs: 39778 / % possible obs: 99.9 % / Redundancy: 6.7 % / CC1/2: 0.984 / Rmerge(I) obs: 0.198 / Net I/σ(I): 6.2
Reflection shellResolution: 2.24→2.3 Å / Redundancy: 6.9 % / Rmerge(I) obs: 0.978 / Mean I/σ(I) obs: 2.2 / Num. unique obs: 2918 / CC1/2: 0.779 / % possible all: 99.9

-
Processing

Software
NameVersionClassification
REFMAC5.8.0257refinement
xia2data reduction
Aimlessdata scaling
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 3PSK

3psk


Resolution: 2.24→56.381 Å / Cor.coef. Fo:Fc: 0.952 / Cor.coef. Fo:Fc free: 0.922 / SU B: 6.949 / SU ML: 0.17 / Cross valid method: FREE R-VALUE / ESU R: 0.249 / ESU R Free: 0.213
Details: Hydrogens have been added in their riding positions
RfactorNum. reflection% reflection
Rfree0.2512 1963 4.943 %
Rwork0.1953 37753 -
all0.198 --
obs-39716 99.882 %
Solvent computationIon probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.2 Å / Solvent model: BABINET MODEL PLUS MASK
Displacement parametersBiso mean: 53.214 Å2
Baniso -1Baniso -2Baniso -3
1--0.015 Å20 Å20 Å2
2--0.763 Å2-0 Å2
3----0.748 Å2
Refinement stepCycle: LAST / Resolution: 2.24→56.381 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms4929 0 155 150 5234
Refine LS restraints
Refine-IDTypeDev idealDev ideal targetNumber
X-RAY DIFFRACTIONr_bond_refined_d0.0070.0135190
X-RAY DIFFRACTIONr_bond_other_d0.0010.0174914
X-RAY DIFFRACTIONr_angle_refined_deg1.4311.6546997
X-RAY DIFFRACTIONr_angle_other_deg1.1941.58811390
X-RAY DIFFRACTIONr_dihedral_angle_1_deg7.0785609
X-RAY DIFFRACTIONr_dihedral_angle_2_deg33.38921.143280
X-RAY DIFFRACTIONr_dihedral_angle_3_deg15.96115890
X-RAY DIFFRACTIONr_dihedral_angle_4_deg20.4151545
X-RAY DIFFRACTIONr_chiral_restr0.0620.2658
X-RAY DIFFRACTIONr_gen_planes_refined0.0060.025822
X-RAY DIFFRACTIONr_gen_planes_other0.0010.021097
X-RAY DIFFRACTIONr_nbd_refined0.1940.2959
X-RAY DIFFRACTIONr_symmetry_nbd_other0.1860.24515
X-RAY DIFFRACTIONr_nbtor_refined0.1640.22431
X-RAY DIFFRACTIONr_symmetry_nbtor_other0.0860.22356
X-RAY DIFFRACTIONr_xyhbond_nbd_refined0.1670.2171
X-RAY DIFFRACTIONr_symmetry_xyhbond_nbd_other0.1250.21
X-RAY DIFFRACTIONr_metal_ion_refined0.1280.22
X-RAY DIFFRACTIONr_symmetry_nbd_refined0.1740.210
X-RAY DIFFRACTIONr_nbd_other0.1940.253
X-RAY DIFFRACTIONr_symmetry_xyhbond_nbd_refined0.1190.29
X-RAY DIFFRACTIONr_mcbond_it5.867.042452
X-RAY DIFFRACTIONr_mcbond_other5.8597.0382450
X-RAY DIFFRACTIONr_mcangle_it8.13315.793056
X-RAY DIFFRACTIONr_mcangle_other8.13315.7953056
X-RAY DIFFRACTIONr_scbond_it7.0797.972738
X-RAY DIFFRACTIONr_scbond_other7.0777.9712739
X-RAY DIFFRACTIONr_scangle_it10.18117.3183941
X-RAY DIFFRACTIONr_scangle_other10.17917.323942
X-RAY DIFFRACTIONr_lrange_it12.04962.5465491
X-RAY DIFFRACTIONr_lrange_other12.05762.5325475
LS refinement shell

Refine-ID: X-RAY DIFFRACTION / Total num. of bins used: 20

Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkRfactor allNum. reflection allFsc freeFsc work% reflection obs (%)WRfactor Rwork
2.24-2.2980.3241490.26227590.26529110.7980.80799.89690.242
2.298-2.3610.2611320.23226710.23328080.8690.86899.82190.215
2.361-2.4290.2971440.23225800.23527310.8420.8799.74370.212
2.429-2.5040.2411280.21525650.21626970.8990.999.85170.191
2.504-2.5860.31150.20624600.2125750.8670.9071000.189
2.586-2.6760.2531120.19823830.224950.9060.9211000.184
2.676-2.7770.2811080.20223190.20624270.9040.9161000.188
2.777-2.890.231090.19422170.19523260.9130.931000.184
2.89-3.0180.291250.18921100.19522350.8990.9361000.182
3.018-3.1650.2711090.18920400.19321510.9080.9399.9070.19
3.165-3.3360.2381050.19419560.19620610.9240.9321000.194
3.336-3.5380.261920.19518390.19819440.920.93599.33130.205
3.538-3.7810.2191000.1817240.18218250.940.94799.94520.195
3.781-4.0820.266850.17316410.17817260.9230.951000.196
4.082-4.4690.211750.15815020.16115770.9450.961000.188
4.469-4.9930.247690.17113820.17414510.940.9541000.21
4.993-5.7580.233780.20412040.20612830.9430.95399.92210.244
5.758-7.0340.249570.20310490.20511120.9360.94699.46040.248
7.034-9.8710.201470.1758400.1778870.9610.9691000.216
9.871-56.3810.312240.3015120.3025380.920.93399.62830.385

+
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