[English] 日本語
Yorodumi
- PDB-8ovz: Crystal structure of D1228V c-MET bound by compound 16 -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 8ovz
TitleCrystal structure of D1228V c-MET bound by compound 16
ComponentsHepatocyte growth factor receptor
KeywordsTRANSFERASE / kinase / inhibitor / cancer research / drug discovery
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 / excitatory postsynaptic potential / liver development / 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 / Immunoglobulin E-set / Tyrosine protein kinases specific active-site signature. / Tyrosine-protein kinase, active site / Serine-threonine/tyrosine-protein kinase, catalytic domain / Protein tyrosine and serine/threonine kinase / 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
Similarity search - Domain/homology
IODIDE ION / Chem-W3N / Hepatocyte growth factor receptor
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.206 Å
AuthorsCollie, G.W.
Funding support1items
OrganizationGrant numberCountry
Not funded
CitationJournal: J.Med.Chem. / Year: 2023
Title: Discovery and Optimization of the First ATP Competitive Type-III c-MET Inhibitor.
Authors: Michaelides, I.N. / Collie, G.W. / Borjesson, U. / Vasalou, C. / Alkhatib, O. / Barlind, L. / Cheung, T. / Dale, I.L. / Embrey, K.J. / Hennessy, E.J. / Khurana, P. / Koh, C.M. / Lamb, M.L. / ...Authors: Michaelides, I.N. / Collie, G.W. / Borjesson, U. / Vasalou, C. / Alkhatib, O. / Barlind, L. / Cheung, T. / Dale, I.L. / Embrey, K.J. / Hennessy, E.J. / Khurana, P. / Koh, C.M. / Lamb, M.L. / Liu, J. / Moss, T.A. / O'Neill, D.J. / Phillips, C. / Shaw, J. / Snijder, A. / Storer, R.I. / Stubbs, C.J. / Han, F. / Li, C. / Qiao, J. / Sun, D.Q. / Wang, J. / Wang, P. / Yang, W.
History
DepositionApr 26, 2023Deposition site: PDBE / Processing site: PDBE
Revision 1.0Jul 5, 2023Provider: repository / Type: Initial release
Revision 1.1Jul 26, 2023Group: Database references / Category: citation / citation_author
Item: _citation.journal_volume / _citation.page_first ..._citation.journal_volume / _citation.page_first / _citation.page_last / _citation_author.identifier_ORCID
Revision 1.2Sep 20, 2023Group: Data collection / Refinement description
Category: chem_comp_atom / chem_comp_bond / pdbx_initial_refinement_model
Item: _pdbx_initial_refinement_model.type

-
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)72,86123
Polymers69,6532
Non-polymers3,20821
Water3,081171
1
A: Hepatocyte growth factor receptor
hetero molecules


Theoretical massNumber of molelcules
Total (without water)36,49412
Polymers34,8261
Non-polymers1,66711
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
2
B: Hepatocyte growth factor receptor
hetero molecules


Theoretical massNumber of molelcules
Total (without water)36,36711
Polymers34,8261
Non-polymers1,54110
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Unit cell
Length a, b, c (Å)53.9, 56.67, 215.81
Angle α, β, γ (deg.)90, 90, 90
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: 34826.363 Da / Num. of mol.: 2 / Mutation: D1228V
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-IOD / IODIDE ION


Mass: 126.904 Da / Num. of mol.: 19 / Source method: obtained synthetically / Formula: I
#3: Chemical ChemComp-W3N / 1-[(1S)-1-[3-(1H-imidazol-4-yl)phenyl]ethyl]-5-(1H-indazol-7-yl)pyrimidine-2,4-dione


Mass: 398.417 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C22H18N6O2 / Feature type: SUBJECT OF INVESTIGATION
#4: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 171 / 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: 2.37 Å3/Da / Density % sol: 48.01 %
Crystal growTemperature: 293 K / Method: vapor diffusion, sitting drop / Details: 12 % PEG 8000, 200 mM NH4I, 0.1 M PCPT pH 7

-
Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: SOLEIL / Beamline: PROXIMA 1 / Wavelength: 0.97857 Å
DetectorType: DECTRIS PILATUS 6M / Detector: PIXEL / Date: Aug 31, 2017
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.97857 Å / Relative weight: 1
ReflectionResolution: 2.21→44.52 Å / Num. obs: 33771 / % possible obs: 98.8 % / Redundancy: 4.8 % / CC1/2: 0.992 / Net I/σ(I): 7.4
Reflection shellResolution: 2.21→2.26 Å / Num. unique obs: 2380 / CC1/2: 0.653

-
Processing

Software
NameVersionClassification
BUSTER2.11.8 (8-JUN-2022)refinement
XDSdata reduction
XDSdata scaling
PHASERphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT / Resolution: 2.206→39.08 Å / Cor.coef. Fo:Fc: 0.92 / Cor.coef. Fo:Fc free: 0.881 / SU R Cruickshank DPI: 0.283 / Cross valid method: THROUGHOUT / SU R Blow DPI: 0.29 / SU Rfree Blow DPI: 0.229 / SU Rfree Cruickshank DPI: 0.228
RfactorNum. reflection% reflectionSelection details
Rfree0.2749 1688 -RANDOM
Rwork0.2245 ---
obs0.227 33732 98.3 %-
Displacement parametersBiso mean: 41.47 Å2
Baniso -1Baniso -2Baniso -3
1-9.3102 Å20 Å20 Å2
2---9.0991 Å20 Å2
3----0.2112 Å2
Refine analyzeLuzzati coordinate error obs: 0.31 Å
Refinement stepCycle: LAST / Resolution: 2.206→39.08 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms4518 0 79 171 4768
Refine LS restraints
Refine-IDTypeDev idealNumberRestraint functionWeight
X-RAY DIFFRACTIONt_bond_d0.0074701HARMONIC2
X-RAY DIFFRACTIONt_angle_deg0.876386HARMONIC2
X-RAY DIFFRACTIONt_dihedral_angle_d1575SINUSOIDAL2
X-RAY DIFFRACTIONt_gen_planes770HARMONIC5
X-RAY DIFFRACTIONt_it4701HARMONIC10
X-RAY DIFFRACTIONt_chiral_improper_torsion596SEMIHARMONIC5
X-RAY DIFFRACTIONt_ideal_dist_contact3609SEMIHARMONIC4
X-RAY DIFFRACTIONt_omega_torsion2.81
X-RAY DIFFRACTIONt_other_torsion15.95
LS refinement shellResolution: 2.21→2.22 Å
RfactorNum. reflection% reflection
Rfree0.466 34 -
Rwork0.3295 --
obs0.336 675 86.75 %
Refinement TLS params.

Refine-ID: X-RAY DIFFRACTION

IDL11 (°2)L12 (°2)L13 (°2)L22 (°2)L23 (°2)L33 (°2)S11 (Å °)S12 (Å °)S13 (Å °)S21 (Å °)S22 (Å °)S23 (Å °)S31 (Å °)S32 (Å °)S33 (Å °)T11 (Å2)T12 (Å2)T13 (Å2)T22 (Å2)T23 (Å2)T33 (Å2)Origin x (Å)Origin y (Å)Origin z (Å)
10-0.77160.86341.4961-2.11953.1475-0.06390.2337-0.32230.2337-0.0333-0.0343-0.3223-0.03430.0973-0.0332-0.0171-0.0165-0.01560.11190.021-4.09455.8091-39.2931
21.16610.16210.41330.1921-0.21970.93550.01920.0258-0.04110.0258-0.05590.073-0.04110.0730.0366-0.02660.01120.006-0.0375-0.026-0.0025-15.41981.3247-42.5521
32.7502-0.640.53740.75620.78950-0.10510.04880.04290.04880.12520.07490.04290.0749-0.020.0073-0.01940.0173-0.1053-0.00070.0276-22.0319.1151-37.8633
41.1471-0.30140.56140-0.5320.82850.21160.0178-0.0310.01780.0561-0.1177-0.031-0.1177-0.26770.0010.01060.0318-0.04080.00480.0188-35.62358.579-41.44
51.6637-0.5973-1.14960.19140.43190.84480.07410.05930.07790.05930.0113-0.22370.0779-0.2237-0.0854-0.0356-0.004-0.0353-0.04260.00560.0299-40.565-3.0829-44.2891
60.89130.81470.88720.53540.14470.7498-0.0446-0.071-0.099-0.0710.0882-0.1224-0.099-0.1224-0.0435-0.0328-0.00460.0449-0.04060.0860.0484-15.7524-13.7746-15.7985
71.139-0.7615-0.12880.23120.06090.6244-0.0382-0.03330.0162-0.03330.0882-0.0730.0162-0.073-0.05-0.041-0.0136-0.0036-0.04660.01060.0458-4.0788-19.6756-20.1304
81.6993-1.3038-0.45460.27431.32411.8872-0.1508-0.3357-0.1061-0.33570.2193-0.115-0.1061-0.115-0.0685-0.04840.0070.00890.00250.0065-0.03672.6181-14.316-12.4593
91.2901-0.39720.46560.2316-0.12260.71040.057-0.00840.0976-0.0084-0.0096-0.10280.0976-0.1028-0.0475-0.0362-0.00360.0075-0.0198-0.0180.023816.1508-18.1243-13.083
101.5670.56650.91361.03050.60290.3760.0943-0.15530.0935-0.1553-0.02940.21510.09350.2151-0.0649-0.00550.02990.0306-0.04710.02420.018721.0195-21.5729-24.5581
Refinement TLS group
IDRefine-IDRefine TLS-IDSelection detailsAuth asym-IDAuth seq-ID
1X-RAY DIFFRACTION1{A|1061 - 1089}A1061 - 1089
2X-RAY DIFFRACTION2{A|1090 - 1213}A1090 - 1213
3X-RAY DIFFRACTION3{A|1214 - 1248}A1214 - 1248
4X-RAY DIFFRACTION4{A|1249 - 1295}A1249 - 1295
5X-RAY DIFFRACTION5{A|1296 - 1346}A1296 - 1346
6X-RAY DIFFRACTION6{B|1057 - 1089}B1057 - 1089
7X-RAY DIFFRACTION7{B|1090 - 1213}B1090 - 1213
8X-RAY DIFFRACTION8{B|1214 - 1248}B1214 - 1248
9X-RAY DIFFRACTION9{B|1249 - 1295}B1249 - 1295
10X-RAY DIFFRACTION10{B|1296 - 1346}B1296 - 1346

+
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