[English] 日本語
Yorodumi
- PDB-3cth: Crystal structure of the tyrosine kinase domain of the hepatocyte... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 3cth
TitleCrystal structure of the tyrosine kinase domain of the hepatocyte growth factor receptor c-met in complex with a aminopyridine based inhibitor
ComponentsHepatocyte growth factor receptorC-Met
KeywordsTRANSFERASE / RECEPTOR TYROSINE KINASE / SIGNAL TRANSDUCTION / GRB2 / SHC / ATP-BINDING / GLYCOPROTEIN / MEMBRANE / NUCLEOTIDE-BINDING / PHOSPHOPROTEIN / PROTO-ONCOGENE / TRANSMEMBRANE / TYROSINE-PROTEIN KINASE
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 / endothelial cell morphogenesis / MET activates STAT3 / negative regulation of hydrogen peroxide-mediated programmed cell death / MET interacts with TNS proteins / MET Receptor Activation / semaphorin receptor activity / positive regulation of endothelial cell chemotaxis ...hepatocyte growth factor receptor activity / negative regulation of guanyl-nucleotide exchange factor activity / Drug-mediated inhibition of MET activation / endothelial cell morphogenesis / MET activates STAT3 / negative regulation of hydrogen peroxide-mediated programmed cell death / MET interacts with TNS proteins / MET Receptor Activation / semaphorin receptor activity / positive regulation of endothelial cell chemotaxis / 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 / 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 / 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 / molecular function activator activity / Negative regulation of MET activity / neuron differentiation / receptor protein-tyrosine kinase / cell surface receptor protein tyrosine kinase signaling pathway / 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 / cell surface receptor signaling pathway / receptor complex / phosphorylation / cell surface / signal transduction / positive regulation of transcription by RNA polymerase II / extracellular region / ATP binding / membrane / identical protein binding / 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 / Immunoglobulin E-set / Tyrosine-protein kinase, catalytic domain / Tyrosine kinase, catalytic domain / Tyrosine protein kinases specific active-site signature. / Tyrosine-protein kinase, active site / Protein tyrosine and serine/threonine kinase / Serine-threonine/tyrosine-protein kinase, catalytic domain / 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-319 / Hepatocyte growth factor receptor
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.3 Å
AuthorsSack, J.
CitationJournal: Bioorg.Med.Chem.Lett. / Year: 2008
Title: Discovery of orally active pyrrolopyridine- and aminopyridine-based Met kinase inhibitors
Authors: Cai, Z.-W. / Wei, D. / Schroeder, G.M. / Cornelius, L.A. / Kim, K. / Chen, X.-T. / Schmidt, R.J. / Williams, D.K. / Tokarski, J.S. / An, Y. / Sack, J.S. / Manne, V. / Kamath, A. / Zhang, Y. ...Authors: Cai, Z.-W. / Wei, D. / Schroeder, G.M. / Cornelius, L.A. / Kim, K. / Chen, X.-T. / Schmidt, R.J. / Williams, D.K. / Tokarski, J.S. / An, Y. / Sack, J.S. / Manne, V. / Kamath, A. / Zhang, Y. / Marathe, P. / Hunt, J.T. / Lombardo, L.J. / Fargnoli, J. / Borzilleri, R.M.
History
DepositionApr 14, 2008Deposition site: RCSB / Processing site: RCSB
Revision 1.0Jun 10, 2008Provider: repository / Type: Initial release
Revision 1.1Jul 13, 2011Group: Version format compliance
Revision 1.2Oct 20, 2021Group: Database references / Derived calculations / Category: database_2 / 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_ref_seq_dif.details / _struct_site.pdbx_auth_asym_id / _struct_site.pdbx_auth_comp_id / _struct_site.pdbx_auth_seq_id
Revision 1.3Feb 21, 2024Group: Data collection / Category: chem_comp_atom / chem_comp_bond

-
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)35,8332
Polymers35,4351
Non-polymers3981
Water1,63991
1


  • Idetical with deposited unit
  • defined by author&software
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
MethodPISA
Unit cell
Length a, b, c (Å)42.752, 47.637, 152.471
Angle α, β, γ (deg.)90.00, 90.00, 90.00
Int Tables number19
Space group name H-MP212121

-
Components

#1: Protein Hepatocyte growth factor receptor / C-Met / E.C.2.7.10.1 / HGF RECEPTOR / SCATTER FACTOR RECEPTOR / SF RECEPTOR / HGF/SF RECEPTOR / MET PROTO-ONCOGENE ...HGF RECEPTOR / SCATTER FACTOR RECEPTOR / SF RECEPTOR / HGF/SF RECEPTOR / MET PROTO-ONCOGENE TYROSINE KINASE / C-MET


Mass: 35435.031 Da / Num. of mol.: 1 / Fragment: TYROSINE KINASE, UNP RESIDUES 1049-1360 / Mutation: YES
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: MET / Cell line (production host): SF9 / Production host: Spodoptera frugiperda (fall armyworm)
References: UniProt: P08581, receptor protein-tyrosine kinase
#2: Chemical ChemComp-319 / N-({4-[(2-aminopyridin-4-yl)oxy]-3-fluorophenyl}carbamoyl)-2-(4-fluorophenyl)acetamide


Mass: 398.363 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C20H16F2N4O3
#3: Water ChemComp-HOH / water / Water


Mass: 18.015 Da / Num. of mol.: 91 / 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: 2.19 Å3/Da / Density % sol: 43.85 %
Crystal growpH: 7.1 / Details: 12% MEPEG 5000, 0.1M HEPES (PH 7.1) 11% 2-PROPANOL

-
Data collection

DiffractionMean temperature: 100 K
Diffraction sourceSource: SYNCHROTRON / Site: APS / Beamline: 32-ID / Wavelength: 1
DetectorType: MAR CCD 165 mm / Detector: CCD / Date: Nov 17, 2004
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1 Å / Relative weight: 1
ReflectionResolution: 2.3→50 Å / Num. obs: 12820 / % possible obs: 88.9 % / Observed criterion σ(I): 0 / Redundancy: 3.2 % / Biso Wilson estimate: 34.269 Å2 / Rmerge(I) obs: 0.108 / Net I/σ(I): 13.5
Reflection shellResolution: 2.3→2.38 Å / Redundancy: 1.7 % / Rmerge(I) obs: 0.635 / Mean I/σ(I) obs: 1.7 / % possible all: 57

-
Processing

Software
NameVersionClassification
BUSTER-TNT2.1.1refinement
HKL-2000(DENZO)data reduction
HKL-2000(SCALEPACK)data scaling
RefinementMethod to determine structure: MOLECULAR REPLACEMENT / Resolution: 2.3→15.25 Å / Cross valid method: THROUGHOUT / σ(F): 0
RfactorNum. reflection% reflectionSelection details
Rfree0.2728 959 7.64 %RANDOM
Rwork0.2069 ---
obs0.2118 12553 87.28 %-
Displacement parametersBiso mean: 56.06 Å2
Baniso -1Baniso -2Baniso -3
1-3.73462295 Å20 Å20 Å2
2--5.26202465 Å20 Å2
3----8.9966476 Å2
Refinement stepCycle: LAST / Resolution: 2.3→15.25 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms2341 0 29 91 2461
Refine LS restraints
Refine-IDTypeDev idealNumberWeight
X-RAY DIFFRACTIONt_bond_d0.00624302
X-RAY DIFFRACTIONt_angle_deg0.9132772
X-RAY DIFFRACTIONt_dihedral_angle_d24.7094710
X-RAY DIFFRACTIONt_incorr_chiral_ct
X-RAY DIFFRACTIONt_pseud_angle
X-RAY DIFFRACTIONt_trig_c_planes0.007502
X-RAY DIFFRACTIONt_gen_planes0.0113505
X-RAY DIFFRACTIONt_it1.394243020
X-RAY DIFFRACTIONt_nbd0.0311085
LS refinement shellResolution: 2.3→2.44 Å / Total num. of bins used: 9
RfactorNum. reflection% reflection
Rfree0.3862 108 8.27 %
Rwork0.3404 1198 -
all0.3441 1306 -
obs--87.28 %

+
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