[English] 日本語
Yorodumi
- PDB-5eyc: Crystal structure of c-Met in complex with naphthyridinone inhibitor 5 -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 5eyc
TitleCrystal structure of c-Met in complex with naphthyridinone inhibitor 5
ComponentsHepatocyte growth factor receptor
KeywordsTRANSFERASE/TRANSFERASE INHIBITOR / phosphotransferase / inhibitor / cancer / TRANSFERASE-TRANSFERASE INHIBITOR complex
Function / homology
Function and homology information


negative regulation of guanyl-nucleotide exchange factor activity / hepatocyte growth factor receptor activity / Drug-mediated inhibition of MET activation / MET activates STAT3 / negative regulation of hydrogen peroxide-mediated programmed cell death / MET Receptor Activation / MET interacts with TNS proteins / endothelial cell morphogenesis / semaphorin receptor activity / MET receptor recycling ...negative regulation of guanyl-nucleotide exchange factor activity / hepatocyte growth factor receptor activity / Drug-mediated inhibition of MET activation / MET activates STAT3 / negative regulation of hydrogen peroxide-mediated programmed cell death / MET Receptor Activation / MET interacts with TNS proteins / 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 / positive regulation of endothelial cell chemotaxis / negative regulation of stress fiber assembly / MET activates PTK2 signaling / branching morphogenesis of an epithelial tube / positive chemotaxis / negative regulation of Rho protein signal transduction / 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 / MECP2 regulates neuronal receptors and channels / positive regulation of microtubule polymerization / negative regulation of autophagy / cell surface receptor protein tyrosine kinase signaling pathway / basal plasma membrane / molecular function activator activity / InlB-mediated entry of Listeria monocytogenes into host cell / excitatory postsynaptic potential / liver development / Negative regulation of MET activity / receptor protein-tyrosine kinase / neuron differentiation / Constitutive Signaling by Aberrant PI3K in Cancer / PIP3 activates AKT signaling / PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling / RAF/MAP kinase cascade / protein tyrosine kinase activity / protein phosphatase binding / cell surface receptor signaling pathway / receptor complex / postsynapse / 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 / IPT domain / PSI domain / domain found in Plexins, Semaphorins and Integrins / Tyrosine-protein kinase, catalytic domain / Tyrosine kinase, catalytic domain / Tyrosine protein kinases specific active-site signature. / Tyrosine-protein kinase, active site / Immunoglobulin E-set / Serine-threonine/tyrosine-protein kinase, catalytic domain / Protein tyrosine and serine/threonine kinase / Phosphorylase Kinase; domain 1 / Phosphorylase Kinase; domain 1 / Transferase(Phosphotransferase) domain 1 / Transferase(Phosphotransferase); 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-5SZ / Hepatocyte growth factor receptor
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / MOLECULAR REPLACEMENT / Resolution: 1.8 Å
AuthorsWhittington, D.A. / Long, A.M.
CitationJournal: J.Med.Chem. / Year: 2016
Title: Discovery of (R)-6-(1-(8-Fluoro-6-(1-methyl-1H-pyrazol-4-yl)-[1,2,4]triazolo[4,3-a]pyridin-3-yl)ethyl)-3-(2-methoxyethoxy)-1,6-naphthyridin-5(6H)-one (AMG 337), a Potent and Selective ...Title: Discovery of (R)-6-(1-(8-Fluoro-6-(1-methyl-1H-pyrazol-4-yl)-[1,2,4]triazolo[4,3-a]pyridin-3-yl)ethyl)-3-(2-methoxyethoxy)-1,6-naphthyridin-5(6H)-one (AMG 337), a Potent and Selective Inhibitor of MET with High Unbound Target Coverage and Robust In Vivo Antitumor Activity.
Authors: Boezio, A.A. / Copeland, K.W. / Rex, K. / K Albrecht, B. / Bauer, D. / Bellon, S.F. / Boezio, C. / Broome, M.A. / Choquette, D. / Coxon, A. / Dussault, I. / Hirai, S. / Lewis, R. / Lin, M.H. ...Authors: Boezio, A.A. / Copeland, K.W. / Rex, K. / K Albrecht, B. / Bauer, D. / Bellon, S.F. / Boezio, C. / Broome, M.A. / Choquette, D. / Coxon, A. / Dussault, I. / Hirai, S. / Lewis, R. / Lin, M.H. / Lohman, J. / Liu, J. / Peterson, E.A. / Potashman, M. / Shimanovich, R. / Teffera, Y. / Whittington, D.A. / Vaida, K.R. / Harmange, J.C.
History
DepositionNov 24, 2015Deposition site: RCSB / Processing site: RCSB
Revision 1.0Feb 10, 2016Provider: repository / Type: Initial release
Revision 1.1Feb 17, 2016Group: Database references
Revision 1.2Apr 6, 2016Group: Database references
Revision 1.3Sep 27, 2023Group: Data collection / Database references ...Data collection / Database references / Derived calculations / Refinement description
Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / citation / database_2 / pdbx_initial_refinement_model / pdbx_struct_oper_list
Item: _citation.journal_id_CSD / _database_2.pdbx_DOI ..._citation.journal_id_CSD / _database_2.pdbx_DOI / _database_2.pdbx_database_accession / _pdbx_struct_oper_list.symmetry_operation

-
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)35,6062
Polymers35,2161
Non-polymers3901
Water4,594255
1


  • Idetical with deposited unit
  • defined by author&software
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
MethodPISA
Unit cell
Length a, b, c (Å)42.073, 43.267, 158.020
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: 35215.715 Da / Num. of mol.: 1 / Fragment: residues 1048-1351
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: MET / Production host: Trichoplusia ni (cabbage looper)
References: UniProt: P08581, receptor protein-tyrosine kinase
#2: Chemical ChemComp-5SZ / 6-[(1~{R})-1-[8-fluoranyl-6-(3-methyl-1,2-oxazol-5-yl)-[1,2,4]triazolo[4,3-a]pyridin-3-yl]ethyl]-1,6-naphthyridin-5-one


Mass: 390.371 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C20H15FN6O2
#3: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 255 / Source method: isolated from a natural source / Formula: H2O

-
Experimental details

-
Experiment

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

-
Sample preparation

CrystalDensity Matthews: 2.04 Å3/Da / Density % sol: 39.77 %
Crystal growTemperature: 293 K / Method: vapor diffusion, hanging drop / pH: 7.8
Details: 12% PEG 4000, 3% (v/v) ethanol, 6% (v/v) isopropanol, 40 mM beta-mercaptoethanol, 100 mM HEPES (pH 7.8)

-
Data collection

DiffractionMean temperature: 100 K
Diffraction sourceSource: ROTATING ANODE / Type: RIGAKU FR-E SUPERBRIGHT / Wavelength: 1.5418 Å
DetectorType: RIGAKU RAXIS IV++ / Detector: IMAGE PLATE / Date: Jun 7, 2011 / Details: Varimax HR
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1.5418 Å / Relative weight: 1
ReflectionResolution: 1.8→50 Å / Num. obs: 22824 / % possible obs: 82.4 % / Observed criterion σ(I): -3 / Redundancy: 2.9 % / Biso Wilson estimate: 28.99 Å2 / Rmerge(I) obs: 0.034 / Χ2: 1.083 / Net I/av σ(I): 20.341 / Net I/σ(I): 24.5 / Num. measured all: 65999
Reflection shell

Diffraction-ID: 1 / Rejects: _

Resolution (Å)Redundancy (%)Rmerge(I) obsMean I/σ(I) obsNum. unique allΧ2% possible all
1.8-1.862.20.3253.68610211.67137.7
1.86-1.942.60.27317111.69663.3
1.94-2.032.90.21723601.52686.6
2.03-2.1330.15923951.40688.4
2.13-2.272.90.1123741.24586.4
2.27-2.442.70.07823291.11284.5
2.44-2.692.50.05324250.91988
2.69-3.082.40.03626480.75395.1
3.08-3.883.10.02827480.56797.4
3.88-503.80.02328130.84293.8

-
Processing

Software
NameVersionClassification
HKL-2000data scaling
REFMAC5.6.0117refinement
PDB_EXTRACT3.15data extraction
CrystalCleardata collection
HKL-2000data reduction
AMoREphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 4XMO

4xmo


Resolution: 1.8→41.74 Å / Cor.coef. Fo:Fc: 0.961 / Cor.coef. Fo:Fc free: 0.937 / WRfactor Rfree: 0.267 / WRfactor Rwork: 0.2014 / FOM work R set: 0.8195 / SU B: 3.44 / SU ML: 0.106 / SU R Cruickshank DPI: 0.1796 / SU Rfree: 0.1671 / Cross valid method: THROUGHOUT / σ(F): 0 / ESU R: 0.18 / ESU R Free: 0.167 / Stereochemistry target values: MAXIMUM LIKELIHOOD
Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS U VALUES : REFINED INDIVIDUALLY
RfactorNum. reflection% reflectionSelection details
Rfree0.2472 1183 5.2 %RANDOM
Rwork0.1917 ---
obs0.1946 21619 82.48 %-
Solvent computationIon probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.2 Å / Solvent model: MASK
Displacement parametersBiso max: 113.16 Å2 / Biso mean: 31.058 Å2 / Biso min: 15.39 Å2
Baniso -1Baniso -2Baniso -3
1--0.51 Å20 Å20 Å2
2--1.91 Å20 Å2
3----1.39 Å2
Refinement stepCycle: final / Resolution: 1.8→41.74 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms2297 0 29 255 2581
Biso mean--27.5 41.05 -
Num. residues----288
Refine LS restraints
Refine-IDTypeDev idealDev ideal targetNumber
X-RAY DIFFRACTIONr_bond_refined_d0.0080.022396
X-RAY DIFFRACTIONr_bond_other_d0.0010.021636
X-RAY DIFFRACTIONr_angle_refined_deg1.1561.9793250
X-RAY DIFFRACTIONr_angle_other_deg0.8553.0013977
X-RAY DIFFRACTIONr_dihedral_angle_1_deg5.185288
X-RAY DIFFRACTIONr_dihedral_angle_2_deg32.9623.2100
X-RAY DIFFRACTIONr_dihedral_angle_3_deg12.99715417
X-RAY DIFFRACTIONr_dihedral_angle_4_deg11.0691514
X-RAY DIFFRACTIONr_chiral_restr0.0660.2361
X-RAY DIFFRACTIONr_gen_planes_refined0.0040.0212600
X-RAY DIFFRACTIONr_gen_planes_other0.0010.02489
LS refinement shellResolution: 1.8→1.847 Å / Total num. of bins used: 20
RfactorNum. reflection% reflection
Rfree0.448 38 -
Rwork0.373 637 -
all-675 -
obs--34.21 %

+
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