[English] 日本語
Yorodumi
- PDB-7b43: Crystal structure of c-MET bound by compound 9 -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 7b43
TitleCrystal structure of c-MET bound by compound 9
ComponentsHepatocyte growth factor receptor
KeywordsTRANSFERASE / c-met / kinase / folded P-loop / inhibitor
Function / homology
Function and homology information


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 Receptor Activation / MET interacts with TNS proteins / endothelial cell morphogenesis / semaphorin receptor activity / MET receptor recycling / pancreas development ...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 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 / negative regulation of stress fiber assembly / positive regulation of endothelial cell chemotaxis / 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 / liver development / molecular function activator activity / InlB-mediated entry of Listeria monocytogenes into host cell / basal plasma membrane / excitatory postsynaptic potential / placental growth factor receptor activity / vascular endothelial growth factor receptor activity / hepatocyte growth factor receptor activity / macrophage colony-stimulating factor receptor activity / platelet-derived growth factor alpha-receptor activity / platelet-derived growth factor beta-receptor activity / boss receptor activity / protein tyrosine kinase collagen receptor activity / brain-derived neurotrophic factor receptor activity / stem cell factor receptor activity / GPI-linked ephrin receptor activity / transmembrane-ephrin receptor activity / epidermal growth factor receptor activity / fibroblast growth factor receptor activity / insulin receptor activity / insulin-like growth factor receptor activity / Negative regulation of MET activity / receptor protein-tyrosine kinase / neuron differentiation / Constitutive Signaling by Aberrant PI3K in Cancer / PIP3 activates AKT signaling / RAF/MAP kinase cascade / PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling / 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-SW5 / Hepatocyte growth factor receptor
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 1.87 Å
AuthorsCollie, G.W.
CitationJournal: Acs Med.Chem.Lett. / Year: 2021
Title: Structural Basis for Targeting the Folded P-Loop Conformation of c-MET.
Authors: Collie, G.W. / Michaelides, I.N. / Embrey, K. / Stubbs, C.J. / Borjesson, U. / Dale, I.L. / Snijder, A. / Barlind, L. / Song, K. / Khurana, P. / Phillips, C. / Storer, R.I.
History
DepositionDec 2, 2020Deposition site: PDBE / Processing site: PDBE
Revision 1.0Dec 9, 2020Provider: repository / Type: Initial release
Revision 1.1Dec 23, 2020Group: Database references / Category: citation / citation_author
Item: _citation.country / _citation.journal_abbrev ..._citation.country / _citation.journal_abbrev / _citation.journal_id_CSD / _citation.journal_id_ISSN / _citation.title / _citation.year
Revision 1.2Feb 3, 2021Group: Database references / Category: citation
Item: _citation.journal_volume / _citation.page_first ..._citation.journal_volume / _citation.page_first / _citation.page_last / _citation.pdbx_database_id_PubMed / _citation.title / _citation.year
Revision 1.3May 1, 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: Hepatocyte growth factor receptor
B: Hepatocyte growth factor receptor
hetero molecules


Theoretical massNumber of molelcules
Total (without water)68,3234
Polymers67,5722
Non-polymers7512
Water2,306128
1
A: Hepatocyte growth factor receptor
hetero molecules


Theoretical massNumber of molelcules
Total (without water)34,1622
Polymers33,7861
Non-polymers3751
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
2
B: Hepatocyte growth factor receptor
hetero molecules


Theoretical massNumber of molelcules
Total (without water)34,1622
Polymers33,7861
Non-polymers3751
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Unit cell
Length a, b, c (Å)42.867, 59.738, 77.603
Angle α, β, γ (deg.)76.510, 73.880, 69.250
Int Tables number1
Space group name H-MP1

-
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: 33786.207 Da / Num. of mol.: 2
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: MET / Production host: Escherichia coli (E. coli)
References: UniProt: P08581, receptor protein-tyrosine kinase
#2: Chemical ChemComp-SW5 / 3-[(4-fluorophenyl)methyl]-5-(1-piperidin-4-ylpyrazol-4-yl)-1~{H}-pyrrolo[2,3-b]pyridine


Mass: 375.442 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C22H22FN5 / Feature type: SUBJECT OF INVESTIGATION
#3: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 128 / 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: 2.61 Å3/Da / Density % sol: 52.91 %
Crystal growTemperature: 293 K / Method: vapor diffusion, sitting drop / Details: 28 % PEGMME2000, 0.1 M bis-tris pH 6.5

-
Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: SLS / Beamline: X06SA / Wavelength: 1.00001 Å
DetectorType: DECTRIS PILATUS 2M / Detector: PIXEL / Date: Sep 17, 2020
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1.00001 Å / Relative weight: 1
ReflectionResolution: 1.87→73.706 Å / Num. obs: 28964 / % possible obs: 70 % / Redundancy: 2.7 % / Biso Wilson estimate: 24.8 Å2 / CC1/2: 0.985 / Rmerge(I) obs: 0.109 / Rpim(I) all: 0.08 / Rrim(I) all: 0.136 / Net I/σ(I): 3.8
Reflection shellResolution: 1.873→2.023 Å / Redundancy: 2.5 % / Rmerge(I) obs: 0.512 / Num. unique obs: 1449 / CC1/2: 0.741 / Rpim(I) all: 0.382 / Rrim(I) all: 0.642 / % possible all: 34.6

-
Processing

Software
NameVersionClassification
Aimlessdata scaling
BUSTER2.11.7refinement
PDB_EXTRACT3.27data extraction
XDSdata reduction
PHASERphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: internal

Resolution: 1.87→18.41 Å / Cor.coef. Fo:Fc: 0.921 / Cor.coef. Fo:Fc free: 0.871 / SU R Cruickshank DPI: 0.298 / Cross valid method: THROUGHOUT / σ(F): 0 / SU R Blow DPI: 0.278 / SU Rfree Blow DPI: 0.219 / SU Rfree Cruickshank DPI: 0.227
RfactorNum. reflection% reflectionSelection details
Rfree0.248 1384 4.79 %RANDOM
Rwork0.2 ---
obs0.203 28882 51.4 %-
Displacement parametersBiso max: 97.47 Å2 / Biso mean: 27.59 Å2 / Biso min: 3 Å2
Baniso -1Baniso -2Baniso -3
1--0.9854 Å2-0.1181 Å2-0.2994 Å2
2--0.3223 Å20.2012 Å2
3---0.6632 Å2
Refine analyzeLuzzati coordinate error obs: 0.31 Å
Refinement stepCycle: final / Resolution: 1.87→18.41 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms4307 0 56 128 4491
Biso mean--29.57 27.38 -
Num. residues----555
Refine LS restraints
Refine-IDTypeNumberRestraint functionWeightDev ideal
X-RAY DIFFRACTIONt_dihedral_angle_d1478SINUSOIDAL2
X-RAY DIFFRACTIONt_trig_c_planes
X-RAY DIFFRACTIONt_gen_planes729HARMONIC5
X-RAY DIFFRACTIONt_it4481HARMONIC20
X-RAY DIFFRACTIONt_nbd
X-RAY DIFFRACTIONt_improper_torsion
X-RAY DIFFRACTIONt_pseud_angle
X-RAY DIFFRACTIONt_chiral_improper_torsion574SEMIHARMONIC5
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_contact5266SEMIHARMONIC4
X-RAY DIFFRACTIONt_bond_d4481HARMONIC20.01
X-RAY DIFFRACTIONt_angle_deg6092HARMONIC21.02
X-RAY DIFFRACTIONt_omega_torsion2.66
X-RAY DIFFRACTIONt_other_torsion18.23
LS refinement shellResolution: 1.87→1.96 Å / Rfactor Rfree error: 0 / Total num. of bins used: 50
RfactorNum. reflection% reflection
Rfree0.2864 29 5.02 %
Rwork0.2199 549 -
all0.2236 578 -
obs--8.14 %

+
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