[English] 日本語
Yorodumi
- PDB-4k3j: Crystal structure of Onartuzumab Fab in complex with MET and HGF-beta -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 4k3j
TitleCrystal structure of Onartuzumab Fab in complex with MET and HGF-beta
Components
  • (Hepatocyte growth ...) x 2
  • (Onartuzumab Fab ...) x 2
KeywordsTransferase/Immune System/Growth Factor / antibody / glycosylation / Transferase-Immune System-Growth Factor complex
Function / homology
Function and homology information


regulation of p38MAPK cascade / skeletal muscle cell proliferation / negative regulation of guanyl-nucleotide exchange factor activity / hepatocyte growth factor receptor activity / regulation of branching involved in salivary gland morphogenesis by mesenchymal-epithelial signaling / 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 ...regulation of p38MAPK cascade / skeletal muscle cell proliferation / negative regulation of guanyl-nucleotide exchange factor activity / hepatocyte growth factor receptor activity / regulation of branching involved in salivary gland morphogenesis by mesenchymal-epithelial signaling / 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 / hepatocyte growth factor receptor signaling pathway / 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 / positive regulation of DNA biosynthetic process / cellular response to hepatocyte growth factor stimulus / branching morphogenesis of an epithelial tube / positive chemotaxis / negative regulation of Rho protein signal transduction / negative regulation of release of cytochrome c from mitochondria / chemoattractant activity / negative regulation of thrombin-activated receptor signaling pathway / negative regulation of interleukin-6 production / semaphorin-plexin signaling pathway / myoblast proliferation / positive regulation of interleukin-10 production / epithelial to mesenchymal transition / establishment of skin barrier / positive regulation of osteoblast differentiation / MET activates RAS signaling / Regulation of MITF-M-dependent genes involved in cell cycle and proliferation / negative regulation of extrinsic apoptotic signaling pathway via death domain receptors / MECP2 regulates neuronal receptors and channels / positive regulation of microtubule polymerization / Interleukin-7 signaling / negative regulation of autophagy / cell surface receptor protein tyrosine kinase signaling pathway / basal plasma membrane / platelet alpha granule lumen / molecular function activator activity / InlB-mediated entry of Listeria monocytogenes into host cell / epithelial cell proliferation / cell chemotaxis / excitatory postsynaptic potential / growth factor activity / liver development / Negative regulation of MET activity / receptor protein-tyrosine kinase / negative regulation of inflammatory response / cell morphogenesis / neuron differentiation / Constitutive Signaling by Aberrant PI3K in Cancer / Platelet degranulation / PIP3 activates AKT signaling / mitotic cell cycle / PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling / RAF/MAP kinase cascade / protein tyrosine kinase activity / Interleukin-4 and Interleukin-13 signaling / protein phosphatase binding / cell surface receptor signaling pathway / positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction / receptor complex / postsynapse / positive regulation of MAPK cascade / positive regulation of cell migration / signaling receptor binding / negative regulation of apoptotic process / cell surface / signal transduction / positive regulation of transcription by RNA polymerase II / extracellular space / extracellular region / ATP binding / identical protein binding / membrane / plasma membrane
Similarity search - Function
Hepatocyte growth factor / Hepatocyte growth factor/Macrophage stimulatory protein / ligand-binding face of the semaphorins, domain 2 / ligand-binding face of the semaphorins, domain 2 / divergent subfamily of APPLE domains / : / Tyrosine-protein kinase, HGF/MSP receptor / Plexin family / Plexin repeat / Plexin repeat ...Hepatocyte growth factor / Hepatocyte growth factor/Macrophage stimulatory protein / ligand-binding face of the semaphorins, domain 2 / ligand-binding face of the semaphorins, domain 2 / divergent subfamily of APPLE domains / : / Tyrosine-protein kinase, HGF/MSP receptor / Plexin family / Plexin repeat / Plexin repeat / Sema domain / semaphorin domain / Sema domain / Sema domain superfamily / Sema domain profile. / PAN/Apple domain profile. / PAN domain / PAN/Apple domain / IPT/TIG domain / ig-like, plexins, transcription factors / IPT domain / PSI domain / domain found in Plexins, Semaphorins and Integrins / Kringle domain / Kringle / Kringle, conserved site / Kringle superfamily / Kringle domain signature. / Kringle domain profile. / Kringle domain / Kringle-like fold / YVTN repeat-like/Quinoprotein amine dehydrogenase / 7 Propeller / Methylamine Dehydrogenase; Chain H / Peptidase S1A, chymotrypsin family / Serine proteases, trypsin domain profile. / Trypsin-like serine protease / Serine proteases, trypsin domain / Trypsin / Tyrosine-protein kinase, catalytic domain / Tyrosine kinase, catalytic domain / Tyrosine protein kinases specific active-site signature. / Tyrosine-protein kinase, active site / Immunoglobulin E-set / Trypsin-like serine proteases / Serine-threonine/tyrosine-protein kinase, catalytic domain / Protein tyrosine and serine/threonine kinase / Thrombin, subunit H / WD40/YVTN repeat-like-containing domain superfamily / Protein kinase, ATP binding site / Protein kinases ATP-binding region signature. / Immunoglobulin-like fold / Peptidase S1, PA clan, chymotrypsin-like fold / Protein kinase domain profile. / Protein kinase domain / Immunoglobulins / Peptidase S1, PA clan / Protein kinase-like domain superfamily / Beta Barrel / Immunoglobulin-like / Sandwich / 2-Layer Sandwich / Mainly Beta / Alpha Beta
Similarity search - Domain/homology
Hepatocyte growth factor receptor / Hepatocyte growth factor
Similarity search - Component
Biological speciesHomo sapiens (human)
Mus musculus (house mouse)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.8 Å
AuthorsMa, X. / Starovasnik, M.A.
CitationJournal: Proc.Natl.Acad.Sci.USA / Year: 2013
Title: Monovalent antibody design and mechanism of action of onartuzumab, a MET antagonist with anti-tumor activity as a therapeutic agent.
Authors: Merchant, M. / Ma, X. / Maun, H.R. / Zheng, Z. / Peng, J. / Romero, M. / Huang, A. / Yang, N.Y. / Nishimura, M. / Greve, J. / Santell, L. / Zhang, Y.W. / Su, Y. / Kaufman, D.W. / Billeci, K. ...Authors: Merchant, M. / Ma, X. / Maun, H.R. / Zheng, Z. / Peng, J. / Romero, M. / Huang, A. / Yang, N.Y. / Nishimura, M. / Greve, J. / Santell, L. / Zhang, Y.W. / Su, Y. / Kaufman, D.W. / Billeci, K.L. / Mai, E. / Moffat, B. / Lim, A. / Duenas, E.T. / Phillips, H.S. / Xiang, H. / Young, J.C. / Vande Woude, G.F. / Dennis, M.S. / Reilly, D.E. / Schwall, R.H. / Starovasnik, M.A. / Lazarus, R.A. / Yansura, D.G.
History
DepositionApr 10, 2013Deposition site: RCSB / Processing site: RCSB
Revision 1.0Aug 28, 2013Provider: repository / Type: Initial release
Revision 1.1May 21, 2014Group: Source and taxonomy
Revision 1.2Aug 20, 2014Group: Source and taxonomy
Revision 1.3Jul 29, 2020Group: Data collection / Database references ...Data collection / Database references / Derived calculations / Structure summary
Category: chem_comp / entity ...chem_comp / entity / pdbx_chem_comp_identifier / pdbx_entity_nonpoly / struct_conn / struct_ref_seq_dif / struct_site / struct_site_gen
Item: _chem_comp.name / _chem_comp.type ..._chem_comp.name / _chem_comp.type / _entity.pdbx_description / _pdbx_entity_nonpoly.name / _struct_conn.pdbx_leaving_atom_flag / _struct_conn.pdbx_role / _struct_ref_seq_dif.details
Description: Carbohydrate remediation / Provider: repository / Type: Remediation
Revision 1.4Sep 20, 2023Group: Data collection / Database references ...Data collection / Database references / Refinement description / Structure summary
Category: chem_comp / chem_comp_atom ...chem_comp / chem_comp_atom / chem_comp_bond / database_2 / pdbx_initial_refinement_model
Item: _chem_comp.pdbx_synonyms / _database_2.pdbx_DOI / _database_2.pdbx_database_accession
Revision 1.5Nov 6, 2024Group: Structure summary / Category: pdbx_entry_details / pdbx_modification_feature

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Hepatocyte growth factor
B: Hepatocyte growth factor beta chain
H: Onartuzumab Fab heavy chain
L: Onartuzumab Fab light chain
hetero molecules


Theoretical massNumber of molelcules
Total (without water)135,3825
Polymers135,1614
Non-polymers2211
Water3,297183
1


  • Idetical with deposited unit
  • defined by author
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Unit cell
Length a, b, c (Å)128.191, 192.228, 65.585
Angle α, β, γ (deg.)90.00, 90.00, 90.00
Int Tables number18
Space group name H-MP21212

-
Components

-
Hepatocyte growth ... , 2 types, 2 molecules AB

#1: Protein Hepatocyte growth factor / Hepatopoietin-A / Scatter factor / SF / Hepatocyte growth factor alpha chain / Hepatocyte growth ...Hepatopoietin-A / Scatter factor / SF / Hepatocyte growth factor alpha chain / Hepatocyte growth factor beta chain


Mass: 26038.086 Da / Num. of mol.: 1 / Fragment: unp residues 495-721 / Mutation: C604S
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: HGF, HPTA / Production host: Trichoplusia ni (cabbage looper) / References: UniProt: P14210
#2: Protein Hepatocyte growth factor beta chain / 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: 60758.867 Da / Num. of mol.: 1 / Fragment: Sema and PSI domain, UNP residues 39-564
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

-
Antibody , 2 types, 2 molecules HL

#3: Antibody Onartuzumab Fab heavy chain


Mass: 24000.809 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Mus musculus, Homo sapiens / Production host: Escherichia coli (E. coli)
#4: Antibody Onartuzumab Fab light chain


Mass: 24363.021 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Mus musculus, Homo sapiens / Production host: Escherichia coli (E. coli)

-
Sugars / Non-polymers , 2 types, 184 molecules

#5: Sugar ChemComp-NAG / 2-acetamido-2-deoxy-beta-D-glucopyranose / N-acetyl-beta-D-glucosamine / 2-acetamido-2-deoxy-beta-D-glucose / 2-acetamido-2-deoxy-D-glucose / 2-acetamido-2-deoxy-glucose / N-ACETYL-D-GLUCOSAMINE


Type: D-saccharide, beta linking / Mass: 221.208 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Formula: C8H15NO6
IdentifierTypeProgram
DGlcpNAcbCONDENSED IUPAC CARBOHYDRATE SYMBOLGMML 1.0
N-acetyl-b-D-glucopyranosamineCOMMON NAMEGMML 1.0
b-D-GlcpNAcIUPAC CARBOHYDRATE SYMBOLPDB-CARE 1.0
GlcNAcSNFG CARBOHYDRATE SYMBOLGMML 1.0
#6: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 183 / Source method: isolated from a natural source / Formula: H2O

-
Details

Has protein modificationY

-
Experimental details

-
Experiment

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

-
Sample preparation

CrystalDensity Matthews: 2.99 Å3/Da / Density % sol: 58.85 %
Crystal growTemperature: 298 K / Method: vapor diffusion, sitting drop / pH: 6.2
Details: 0.1 M sodium cacodylate pH 6.2, 20% (w/v) PEG 4000, VAPOR DIFFUSION, SITTING DROP, temperature 298K

-
Data collection

DiffractionMean temperature: 100 K
Diffraction sourceSource: SYNCHROTRON / Site: ALS / Beamline: 5.0.2 / Wavelength: 1 Å
DetectorType: ADSC QUANTUM 315 / Detector: CCD / Date: Apr 11, 2011
RadiationMonochromator: Si 111 / Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1 Å / Relative weight: 1
ReflectionResolution: 2.8→50 Å / Num. obs: 40382 / % possible obs: 98.9 % / Redundancy: 4 % / Rsym value: 0.074 / Net I/σ(I): 15.56
Reflection shellResolution: 2.8→2.9 Å / Redundancy: 3.8 % / Mean I/σ(I) obs: 1.88 / Num. unique all: 3938 / Rsym value: 0.513 / % possible all: 98

-
Processing

Software
NameVersionClassification
Blu-Icedata collection
PHASESphasing
REFMAC5.5.0109refinement
HKL-2000data reduction
HKL-2000data scaling
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: PDB ENTRY 1SHY

1shy


Resolution: 2.8→50 Å / Cor.coef. Fo:Fc: 0.927 / Cor.coef. Fo:Fc free: 0.902 / SU B: 29.924 / SU ML: 0.266 / Cross valid method: THROUGHOUT / ESU R: 1.704 / ESU R Free: 0.356 / Stereochemistry target values: MAXIMUM LIKELIHOOD / Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS
RfactorNum. reflection% reflectionSelection details
Rfree0.25287 2027 5 %RANDOM
Rwork0.21083 ---
obs0.21297 38286 98.87 %-
Solvent computationIon probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.4 Å / Solvent model: MASK
Displacement parametersBiso mean: 52.103 Å2
Baniso -1Baniso -2Baniso -3
1-0.2 Å2-0 Å20 Å2
2---1.04 Å2-0 Å2
3---0.83 Å2
Refinement stepCycle: LAST / Resolution: 2.8→50 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms9084 0 14 183 9281
Refine LS restraints
Refine-IDTypeDev idealDev ideal targetNumber
X-RAY DIFFRACTIONr_bond_refined_d0.0070.0229343
X-RAY DIFFRACTIONr_bond_other_d
X-RAY DIFFRACTIONr_angle_refined_deg1.051.94912708
X-RAY DIFFRACTIONr_angle_other_deg
X-RAY DIFFRACTIONr_dihedral_angle_1_deg5.95751157
X-RAY DIFFRACTIONr_dihedral_angle_2_deg34.18924.099405
X-RAY DIFFRACTIONr_dihedral_angle_3_deg15.059151517
X-RAY DIFFRACTIONr_dihedral_angle_4_deg14.2991543
X-RAY DIFFRACTIONr_chiral_restr0.0690.21408
X-RAY DIFFRACTIONr_gen_planes_refined0.0050.0217081
X-RAY DIFFRACTIONr_gen_planes_other
X-RAY DIFFRACTIONr_nbd_refined
X-RAY DIFFRACTIONr_nbd_other
X-RAY DIFFRACTIONr_nbtor_refined
X-RAY DIFFRACTIONr_nbtor_other
X-RAY DIFFRACTIONr_xyhbond_nbd_refined
X-RAY DIFFRACTIONr_xyhbond_nbd_other
X-RAY DIFFRACTIONr_metal_ion_refined
X-RAY DIFFRACTIONr_metal_ion_other
X-RAY DIFFRACTIONr_symmetry_vdw_refined
X-RAY DIFFRACTIONr_symmetry_vdw_other
X-RAY DIFFRACTIONr_symmetry_hbond_refined
X-RAY DIFFRACTIONr_symmetry_hbond_other
X-RAY DIFFRACTIONr_symmetry_metal_ion_refined
X-RAY DIFFRACTIONr_symmetry_metal_ion_other
X-RAY DIFFRACTIONr_mcbond_it0.4491.55795
X-RAY DIFFRACTIONr_mcbond_other
X-RAY DIFFRACTIONr_mcangle_it0.85829404
X-RAY DIFFRACTIONr_scbond_it0.98233548
X-RAY DIFFRACTIONr_scangle_it1.7354.53304
X-RAY DIFFRACTIONr_rigid_bond_restr
X-RAY DIFFRACTIONr_sphericity_free
X-RAY DIFFRACTIONr_sphericity_bonded
LS refinement shellResolution: 2.8→2.874 Å / Total num. of bins used: 20
RfactorNum. reflection% reflection
Rfree0.342 156 -
Rwork0.324 2739 -
obs--97.51 %
Refinement TLS params.

Method: refined / 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)
13.3001-1.51941.07633.9964-0.38643.0652-0.114-0.10380.35720.3418-0.04-0.5482-0.21030.30090.1540.0842-0.0188-0.05520.04920.00410.08514.981482.471910.1408
28.279-5.31195.790710.37343.004610.56920.5461-0.8315-1.61680.6523-1.17272.87291.1968-2.42490.62650.5929-0.10160.29451.0656-0.00390.9751-7.212273.322315.6565
34.3856-3.0075-0.0855.9175-0.50183.9426-0.2614-0.55050.17580.80950.23840.033-0.0685-0.1070.0230.22680.00090.03290.0954-0.01690.03575.205777.9915.903
44.47860.03891.46523.13550.51773.2651-0.12710.2620.7261-0.30770.12740.4358-0.45-0.1391-0.00030.1524-0.0427-0.05730.12550.12690.2325-11.474475.1304-15.4946
51.48270.31880.12942.843-0.41311.82660.00730.2113-0.2474-0.48320.0487-0.24360.27470.2416-0.0560.2086-0.0271-0.01960.15190.00330.08492.416553.9394-18.5801
63.38451.8694-0.52721.52160.04510.3162-0.0481-0.09840.22330.1201-0.13840.45620.0825-0.04940.18650.4114-0.1708-0.12460.4140.13820.5215-27.589645.7405-13.1449
70.5383-1.0060.81583.0625-1.91251.76140.22760.1774-0.0158-0.2288-0.3869-0.18390.17840.47090.15920.2697-0.01960.00370.34160.11540.254214.131416.15257.2439
81.1596-0.90340.87131.5618-1.13071.5934-0.0223-0.0798-0.05120.3284-0.0193-0.1078-0.19080.18120.04150.2632-0.0614-0.06710.26920.0950.24128.035720.0823.7848
Refinement TLS group
IDRefine-IDRefine TLS-IDAuth asym-IDAuth seq-ID
1X-RAY DIFFRACTION1A495 - 636
2X-RAY DIFFRACTION2A637 - 661
3X-RAY DIFFRACTION3A662 - 721
4X-RAY DIFFRACTION4B39 - 212
5X-RAY DIFFRACTION5B213 - 454
6X-RAY DIFFRACTION6B455 - 564
7X-RAY DIFFRACTION7H1 - 215
8X-RAY DIFFRACTION8L1 - 211

+
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