[English] 日本語
Yorodumi
- PDB-3q6w: Structure of dually-phosphorylated MET receptor kinase in complex... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 3q6w
TitleStructure of dually-phosphorylated MET receptor kinase in complex with an MK-2461 analog with specificity for the activated receptor
ComponentsHepatocyte growth factor receptor
Keywordstransferase/transferase inhibitor / Tyrosine Kinase / two phosphotyrosine resiudes / transferase-transferase inhibitor complex
Function / homology
Function and homology information


hepatocyte growth factor receptor activity / negative regulation of guanyl-nucleotide exchange factor activity / Drug-mediated inhibition of MET activation / MET activates STAT3 / negative regulation of hydrogen peroxide-mediated programmed cell death / MET interacts with TNS proteins / MET Receptor Activation / endothelial cell morphogenesis / semaphorin receptor activity / MET receptor recycling ...hepatocyte growth factor receptor activity / negative regulation of guanyl-nucleotide exchange factor activity / Drug-mediated inhibition of MET activation / MET activates STAT3 / negative regulation of hydrogen peroxide-mediated programmed cell death / MET interacts with TNS proteins / MET Receptor Activation / endothelial cell morphogenesis / semaphorin receptor activity / MET receptor recycling / pancreas development / MET activates PTPN11 / MET activates RAP1 and RAC1 / Sema4D mediated inhibition of cell attachment and migration / MET activates PI3K/AKT signaling / negative regulation of stress fiber assembly / positive regulation of endothelial cell chemotaxis / negative regulation of Rho protein signal transduction / MET activates PTK2 signaling / branching morphogenesis of an epithelial tube / positive chemotaxis / negative regulation of thrombin-activated receptor signaling pathway / semaphorin-plexin signaling pathway / establishment of skin barrier / MET activates RAS signaling / Regulation of MITF-M-dependent genes involved in cell cycle and proliferation / phagocytosis / MECP2 regulates neuronal receptors and channels / positive regulation of microtubule polymerization / negative regulation of autophagy / basal plasma membrane / InlB-mediated entry of Listeria monocytogenes into host cell / liver development / excitatory postsynaptic potential / molecular function activator activity / Negative regulation of MET activity / receptor protein-tyrosine kinase / neuron differentiation / Constitutive Signaling by Aberrant PI3K in Cancer / cell migration / PIP3 activates AKT signaling / nervous system development / PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling / RAF/MAP kinase cascade / protein tyrosine kinase activity / protein phosphatase binding / postsynapse / receptor complex / cell surface receptor signaling pathway / cell surface / signal transduction / positive regulation of transcription by RNA polymerase II / extracellular region / ATP binding / identical protein binding / membrane / plasma membrane
Similarity search - Function
Tyrosine-protein kinase, HGF/MSP receptor / Plexin family / Plexin repeat / Plexin repeat / Sema domain / semaphorin domain / Sema domain / Sema domain superfamily / Sema domain profile. / IPT/TIG domain ...Tyrosine-protein kinase, HGF/MSP receptor / Plexin family / Plexin repeat / Plexin repeat / Sema domain / semaphorin domain / Sema domain / Sema domain superfamily / Sema domain profile. / IPT/TIG domain / ig-like, plexins, transcription factors / PSI domain / domain found in Plexins, Semaphorins and Integrins / IPT domain / Tyrosine-protein kinase, catalytic domain / Tyrosine kinase, catalytic domain / Tyrosine protein kinases specific active-site signature. / Immunoglobulin E-set / 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 / WD40/YVTN repeat-like-containing domain superfamily / Protein kinase, ATP binding site / Protein kinases ATP-binding region signature. / Immunoglobulin-like fold / 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-Q6W / Hepatocyte growth factor receptor
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / molecular replacement / Resolution: 1.75 Å
AuthorsSoisson, S.M. / Rickert, K.W. / Patel, S.B. / Lumb, K.J.
CitationJournal: J.Biol.Chem. / Year: 2011
Title: Structural basis for selective small molecule kinase inhibition of activated c-Met.
Authors: Rickert, K.W. / Patel, S.B. / Allison, T.J. / Byrne, N.J. / Darke, P.L. / Ford, R.E. / Guerin, D.J. / Hall, D.L. / Kornienko, M. / Lu, J. / Munshi, S.K. / Reid, J.C. / Shipman, J.M. / ...Authors: Rickert, K.W. / Patel, S.B. / Allison, T.J. / Byrne, N.J. / Darke, P.L. / Ford, R.E. / Guerin, D.J. / Hall, D.L. / Kornienko, M. / Lu, J. / Munshi, S.K. / Reid, J.C. / Shipman, J.M. / Stanton, E.F. / Wilson, K.J. / Young, J.R. / Soisson, S.M. / Lumb, K.J.
History
DepositionJan 3, 2011Deposition site: RCSB / Processing site: RCSB
Revision 1.0Jan 19, 2011Provider: repository / Type: Initial release
Revision 1.1Jul 13, 2011Group: Version format compliance
Revision 1.2Nov 8, 2017Group: Refinement description / Category: software / Item: _software.name
Revision 1.3Nov 6, 2024Group: Data collection / Database references ...Data collection / Database references / Derived calculations / Structure summary
Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / database_2 / pdbx_entry_details / pdbx_modification_feature / struct_conn / struct_ref_seq_dif / 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_ref_seq_dif.details / _struct_site.pdbx_auth_asym_id / _struct_site.pdbx_auth_comp_id / _struct_site.pdbx_auth_seq_id

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Hepatocyte growth factor receptor
hetero molecules


Theoretical massNumber of molelcules
Total (without water)35,6322
Polymers35,1131
Non-polymers5191
Water2,882160
1


  • Idetical with deposited unit
  • defined by software
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
MethodPISA
Unit cell
Length a, b, c (Å)42.895, 64.091, 111.107
Angle α, β, γ (deg.)90.000, 90.000, 90.000
Int Tables number19
Space group name H-MP212121

-
Components

#1: Protein Hepatocyte growth factor receptor / HGF receptor / HGF/SF receptor / Proto-oncogene c-Met / Scatter factor receptor / SF receptor / ...HGF receptor / HGF/SF receptor / Proto-oncogene c-Met / Scatter factor receptor / SF receptor / Tyrosine-protein kinase Met


Mass: 35113.367 Da / Num. of mol.: 1 / Fragment: residues 1048-1348, Kinase Domain
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: MET / Production host: Spodoptera frugiperda (fall armyworm) / Strain (production host): Sf21
References: UniProt: P08581, receptor protein-tyrosine kinase
#2: Chemical ChemComp-Q6W / 3-{5-oxo-3-[1-(piperidin-4-yl)-1H-pyrazol-4-yl]-5H-benzo[4,5]cyclohepta[1,2-b]pyridin-7-yl}-N-(pyridin-2-ylmethyl)propanamide


Mass: 518.609 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C31H30N6O2
#3: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 160 / Source method: isolated from a natural source / Formula: H2O
Has protein modificationY

-
Experimental details

-
Experiment

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

-
Sample preparation

CrystalDensity Matthews: 2.17 Å3/Da / Density % sol: 43.44 %
Crystal growTemperature: 293 K / Method: vapor diffusion, sitting drop / pH: 7
Details: 15.6 mg/ml protein mixed 1:1 with a reservoir solution of 150 mM malic acid, 20% PEG3350. 2-fold molar excess of ligand was added for co-crystallization., pH 7.0, VAPOR DIFFUSION, SITTING DROP, temperature 293K

-
Data collection

DiffractionMean temperature: 100 K
Diffraction sourceSource: SYNCHROTRON / Site: APS / Beamline: 17-ID / Wavelength: 1 Å
DetectorType: ADSC QUANTUM 210 / Detector: CCD / Date: May 2, 2009
RadiationMonochromator: Si 111 / Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1 Å / Relative weight: 1
ReflectionResolution: 1.75→50 Å / Num. all: 31477 / Num. obs: 31477 / % possible obs: 98.7 % / Observed criterion σ(F): 1 / Observed criterion σ(I): 1 / Redundancy: 7 % / Rmerge(I) obs: 0.054 / Χ2: 1.139 / Net I/σ(I): 14.1
Reflection shell
Resolution (Å)Redundancy (%)Rmerge(I) obsNum. unique allΧ2Diffraction-ID% possible all
1.75-1.787.10.54115781.1561100
1.78-1.817.20.4615361.1531100
1.81-1.857.30.41815801.2491100
1.85-1.897.20.3415991.1971100
1.89-1.937.20.30215321.3311100
1.93-1.977.20.24315691.2631100
1.97-2.027.30.18915881.1611100
2.02-2.077.20.15715581.267199.9
2.07-2.147.30.1315851.2331100
2.14-2.27.30.10415611.2451100
2.2-2.287.20.09815911.3191100
2.28-2.387.30.07315871.071199.9
2.38-2.487.30.06515801.0571100
2.48-2.617.20.05915820.9531100
2.61-2.787.20.05216000.941199.9
2.78-2.997.10.04516021.0671100
2.99-3.2970.03916221.058199.8
3.29-3.776.80.03616061.035199.1
3.77-4.7560.03315481.004193.5
4.75-505.50.0314730.929183.6

-
Phasing

PhasingMethod: molecular replacement

-
Processing

Software
NameVersionClassificationNB
SCALEPACKdata scaling
MOLREPphasing
BUSTER-TNTBUSTER 2.9.4refinement
PDB_EXTRACT3.1data extraction
ADSCQuantumdata collection
DENZOdata reduction
HKL-2000data scaling
BUSTER2.9.4refinement
RefinementMethod to determine structure: MOLECULAR REPLACEMENT / Resolution: 1.75→41.98 Å / Cor.coef. Fo:Fc: 0.9338 / Cor.coef. Fo:Fc free: 0.9224 / Occupancy max: 1 / Occupancy min: 1 / Cross valid method: THROUGHOUT / σ(F): 0 / Stereochemistry target values: Engh & Huber
RfactorNum. reflection% reflectionSelection details
Rfree0.2269 1578 5.05 %RANDOM
Rwork0.2038 ---
all0.205 31249 --
obs0.205 31249 98.63 %-
Displacement parametersBiso max: 142.1 Å2 / Biso mean: 35.3046 Å2 / Biso min: 18.23 Å2
Baniso -1Baniso -2Baniso -3
1--7.1478 Å20 Å20 Å2
2---2.3309 Å20 Å2
3---9.4787 Å2
Refine analyzeLuzzati coordinate error obs: 0.214 Å
Refinement stepCycle: LAST / Resolution: 1.75→41.98 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms2404 0 39 160 2603
Refine LS restraints
Refine-IDTypeNumberWeightDev ideal
X-RAY DIFFRACTIONt_dihedral_angle_d8412
X-RAY DIFFRACTIONt_trig_c_planes508
X-RAY DIFFRACTIONt_gen_planes3728
X-RAY DIFFRACTIONt_it251120
X-RAY DIFFRACTIONt_nbd
X-RAY DIFFRACTIONt_improper_torsion
X-RAY DIFFRACTIONt_pseud_angle
X-RAY DIFFRACTIONt_chiral_improper_torsion3085
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_contact29514
X-RAY DIFFRACTIONt_bond_d251120.01
X-RAY DIFFRACTIONt_angle_deg340621.18
X-RAY DIFFRACTIONt_omega_torsion2.43
X-RAY DIFFRACTIONt_other_torsion16.78
LS refinement shellResolution: 1.75→1.81 Å / Total num. of bins used: 16
RfactorNum. reflection% reflection
Rfree0.2688 149 5.21 %
Rwork0.2259 2711 -
all0.2281 2860 -
obs--98.63 %

+
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