[English] 日本語
Yorodumi
- PDB-5sx4: Crystal Structure of panitumumab in complex with epidermal growth... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 5sx4
TitleCrystal Structure of panitumumab in complex with epidermal growth factor receptor domain 3.
Components
  • (Panitumumab Fab ...) x 2
  • Epidermal growth factor receptor
KeywordsTRANSFERASE/IMMUNE SYSTEM / Cetuximab / panitumumab / EGFR / Vectibix / Erbitux / TRANSFERASE-IMMUNE SYSTEM complex
Function / homology
Function and homology information


response to hydroxyisoflavone / multivesicular body, internal vesicle lumen / positive regulation of prolactin secretion / negative regulation of cardiocyte differentiation / positive regulation of protein kinase C activity / diterpenoid metabolic process / Shc-EGFR complex / ovulation cycle / Inhibition of Signaling by Overexpressed EGFR / epidermal growth factor receptor activity ...response to hydroxyisoflavone / multivesicular body, internal vesicle lumen / positive regulation of prolactin secretion / negative regulation of cardiocyte differentiation / positive regulation of protein kinase C activity / diterpenoid metabolic process / Shc-EGFR complex / ovulation cycle / Inhibition of Signaling by Overexpressed EGFR / epidermal growth factor receptor activity / EGFR interacts with phospholipase C-gamma / positive regulation of mucus secretion / response to UV-A / epidermal growth factor binding / PLCG1 events in ERBB2 signaling / tongue development / midgut development / ERBB2-EGFR signaling pathway / hydrogen peroxide metabolic process / PTK6 promotes HIF1A stabilization / digestive tract morphogenesis / morphogenesis of an epithelial fold / ERBB2 Activates PTK6 Signaling / intracellular vesicle / Signaling by EGFR / response to cobalamin / transmembrane receptor protein tyrosine kinase activator activity / protein tyrosine kinase activator activity / negative regulation of epidermal growth factor receptor signaling pathway / Signaling by ERBB4 / eyelid development in camera-type eye / regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction / protein insertion into membrane / cerebral cortex cell migration / ERBB2 Regulates Cell Motility / Respiratory syncytial virus (RSV) attachment and entry / regulation of JNK cascade / : / PI3K events in ERBB2 signaling / positive regulation of cyclin-dependent protein serine/threonine kinase activity / negative regulation of mitotic cell cycle / hair follicle development / Estrogen-dependent nuclear events downstream of ESR-membrane signaling / MAP kinase kinase kinase activity / embryonic placenta development / positive regulation of bone resorption / positive regulation of G1/S transition of mitotic cell cycle / GAB1 signalosome / salivary gland morphogenesis / peptidyl-tyrosine autophosphorylation / regulation of peptidyl-tyrosine phosphorylation / positive regulation of phosphorylation / positive regulation of glial cell proliferation / positive regulation of vasoconstriction / Signaling by ERBB2 / cellular response to epidermal growth factor stimulus / GRB2 events in EGFR signaling / SHC1 events in EGFR signaling / cellular response to cadmium ion / EGFR Transactivation by Gastrin / positive regulation of DNA repair / GRB2 events in ERBB2 signaling / TFAP2 (AP-2) family regulates transcription of growth factors and their receptors / transmembrane receptor protein tyrosine kinase activity / SHC1 events in ERBB2 signaling / positive regulation of synaptic transmission, glutamatergic / cellular response to dexamethasone stimulus / ossification / neurogenesis / regulation of ERK1 and ERK2 cascade / basal plasma membrane / neuron projection morphogenesis / positive regulation of superoxide anion generation / positive regulation of DNA replication / epithelial cell proliferation / Signal transduction by L1 / cellular response to estradiol stimulus / positive regulation of epithelial cell proliferation / NOTCH3 Activation and Transmission of Signal to the Nucleus / astrocyte activation / liver regeneration / positive regulation of protein localization to plasma membrane / EGFR downregulation / cellular response to amino acid stimulus / positive regulation of smooth muscle cell proliferation / Signaling by ERBB2 TMD/JMD mutants / positive regulation of MAP kinase activity / lung development / clathrin-coated endocytic vesicle membrane / Constitutive Signaling by EGFRvIII / Signaling by ERBB2 ECD mutants / Signaling by ERBB2 KD Mutants / epidermal growth factor receptor signaling pathway / negative regulation of protein catabolic process / receptor protein-tyrosine kinase / Downregulation of ERBB2 signaling / kinase binding / ruffle membrane / positive regulation of miRNA transcription / cell-cell adhesion
Similarity search - Function
24 nucleotide stem-loop, u2 snrnp hairpin iv. U2 a'; Chain A / Receptor L-domain / : / Epidermal growth factor receptor transmembrane-juxtamembrane segment / Tyrosine protein kinase, EGF/ERB/XmrK receptor / Growth factor receptor domain 4 / Growth factor receptor domain IV / Alpha-Beta Horseshoe / Receptor L-domain / Furin-like cysteine-rich domain ...24 nucleotide stem-loop, u2 snrnp hairpin iv. U2 a'; Chain A / Receptor L-domain / : / Epidermal growth factor receptor transmembrane-juxtamembrane segment / Tyrosine protein kinase, EGF/ERB/XmrK receptor / Growth factor receptor domain 4 / Growth factor receptor domain IV / Alpha-Beta Horseshoe / Receptor L-domain / Furin-like cysteine-rich domain / Receptor L-domain superfamily / Furin-like cysteine rich region / Receptor L domain / Furin-like repeat / Furin-like repeats / Growth factor receptor cysteine-rich domain superfamily / 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 / Immunoglobulins / Protein kinase, ATP binding site / Protein kinases ATP-binding region signature. / Protein kinase domain profile. / Protein kinase domain / Protein kinase-like domain superfamily / Immunoglobulin-like / Sandwich / Mainly Beta / Alpha Beta
Similarity search - Domain/homology
Epidermal growth factor receptor
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.8 Å
AuthorsSickmier, E.A. / Kurzeja, R.J.M. / Michelsen, K. / Mukta, V. / Yang, E. / Tasker, A.S.
CitationJournal: Plos One / Year: 2016
Title: The Panitumumab EGFR Complex Reveals a Binding Mechanism That Overcomes Cetuximab Induced Resistance.
Authors: Sickmier, E.A. / Kurzeja, R.J. / Michelsen, K. / Vazir, M. / Yang, E. / Tasker, A.S.
History
DepositionAug 9, 2016Deposition site: RCSB / Processing site: RCSB
Revision 1.0Oct 5, 2016Provider: repository / Type: Initial release
Revision 1.1Oct 4, 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 / database_2 / pdbx_initial_refinement_model / pdbx_struct_oper_list
Item: _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
I: Panitumumab Fab Light Chain
J: Panitumumab Fab Heavy Chain
L: Panitumumab Fab Light Chain
H: Panitumumab Fab Heavy Chain
M: Epidermal growth factor receptor
N: Epidermal growth factor receptor
hetero molecules


Theoretical massNumber of molelcules
Total (without water)140,06818
Polymers138,6696
Non-polymers1,39912
Water2,108117
1
I: Panitumumab Fab Light Chain
J: Panitumumab Fab Heavy Chain
M: Epidermal growth factor receptor
hetero molecules


Theoretical massNumber of molelcules
Total (without water)69,9538
Polymers69,3353
Non-polymers6195
Water543
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area6290 Å2
ΔGint-67 kcal/mol
Surface area26580 Å2
MethodPISA
2
L: Panitumumab Fab Light Chain
H: Panitumumab Fab Heavy Chain
N: Epidermal growth factor receptor
hetero molecules


Theoretical massNumber of molelcules
Total (without water)70,11510
Polymers69,3353
Non-polymers7817
Water543
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area6650 Å2
ΔGint-81 kcal/mol
Surface area27060 Å2
MethodPISA
Unit cell
Length a, b, c (Å)65.273, 113.184, 232.443
Angle α, β, γ (deg.)90.000, 90.000, 90.000
Int Tables number19
Space group name H-MP212121

-
Components

-
Protein , 1 types, 2 molecules MN

#3: Protein Epidermal growth factor receptor / Proto-oncogene c-ErbB-1 / Receptor tyrosine-protein kinase erbB-1


Mass: 22280.316 Da / Num. of mol.: 2 / Fragment: UNP residues 335-525
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: EGFR, ERBB, ERBB1, HER1 / Production host: Spodoptera frugiperda (fall armyworm)
References: UniProt: P00533, receptor protein-tyrosine kinase

-
Antibody , 2 types, 4 molecules ILJH

#1: Antibody Panitumumab Fab Light Chain


Mass: 23379.875 Da / Num. of mol.: 2
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Production host: Cricetulus griseus (Chinese hamster)
#2: Antibody Panitumumab Fab Heavy Chain


Mass: 23674.430 Da / Num. of mol.: 2
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Production host: Cricetulus griseus (Chinese hamster)

-
Non-polymers , 5 types, 129 molecules

#4: Chemical
ChemComp-SO4 / SULFATE ION


Mass: 96.063 Da / Num. of mol.: 8 / Source method: obtained synthetically / Formula: SO4
#5: Chemical ChemComp-GOL / GLYCEROL / GLYCERIN / PROPANE-1,2,3-TRIOL


Mass: 92.094 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C3H8O3
#6: Chemical ChemComp-1PE / PENTAETHYLENE GLYCOL / PEG400


Mass: 238.278 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C10H22O6 / Comment: precipitant*YM
#7: Chemical ChemComp-EDO / 1,2-ETHANEDIOL / ETHYLENE GLYCOL


Mass: 62.068 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C2H6O2
#8: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 117 / 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: 3.1 Å3/Da / Density % sol: 60.27 %
Crystal growTemperature: 293 K / Method: vapor diffusion, hanging drop / Details: 2.0 M AmSO4, 100 mM MES 6.5 and 5% peg 400

-
Data collection

DiffractionMean temperature: 80 K
Diffraction sourceSource: SYNCHROTRON / Site: ALS / Beamline: 5.0.2 / Wavelength: 1 Å
DetectorType: ADSC QUANTUM 315 / Detector: CCD / Date: May 17, 2013
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1 Å / Relative weight: 1
ReflectionResolution: 2.8→30 Å / Num. obs: 43522 / % possible obs: 99.6 % / Redundancy: 6 % / Biso Wilson estimate: 36.13 Å2 / Rmerge(I) obs: 0.098 / Χ2: 0.95 / Net I/av σ(I): 14.637 / Net I/σ(I): 13.4 / Num. measured all: 261344
Reflection shell
Resolution (Å)Redundancy (%)Rmerge(I) obsDiffraction-ID% possible all
2.8-2.95.20.502198.6
2.9-3.025.30.333198.9
3.02-3.155.40.235199.3
3.15-3.325.50.169199.7
3.32-3.535.70.144199.9
3.53-3.860.128199.9
3.8-4.186.40.1171100
4.18-4.786.80.1041100
4.78-6.026.80.0871100
6.02-306.70.057199.7

-
Processing

Software
NameVersionClassification
SCALEPACKdata scaling
PHENIXdev_2356refinement
PDB_EXTRACT3.2data extraction
HKL-2000data reduction
PHASERphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 1YY9

1yy9


Resolution: 2.8→29.596 Å / SU ML: 0.34 / Cross valid method: FREE R-VALUE / σ(F): 1.34 / Phase error: 29.01
RfactorNum. reflection% reflection
Rfree0.2661 1974 5.05 %
Rwork0.2233 --
obs0.2255 39087 88.15 %
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å
Displacement parametersBiso max: 148.15 Å2 / Biso mean: 54.6188 Å2 / Biso min: 8.95 Å2
Refinement stepCycle: final / Resolution: 2.8→29.596 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms9305 0 82 117 9504
Biso mean--70.32 32.08 -
Num. residues----1218
Refine LS restraints
Refine-IDTypeDev idealNumber
X-RAY DIFFRACTIONf_bond_d0.0029592
X-RAY DIFFRACTIONf_angle_d0.48513034
X-RAY DIFFRACTIONf_chiral_restr0.0431484
X-RAY DIFFRACTIONf_plane_restr0.0041650
X-RAY DIFFRACTIONf_dihedral_angle_d11.3355739
LS refinement shell

Refine-ID: X-RAY DIFFRACTION / Total num. of bins used: 14

Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkNum. reflection all% reflection obs (%)
2.8-2.84730.3786510.3161120117137
2.8473-2.92420.37341070.29081857196464
2.9242-3.01020.35271010.30122122222371
3.0102-3.10720.33621440.28392353249779
3.1072-3.21820.32781280.26132640276889
3.2182-3.34680.26211620.2582842300496
3.3468-3.49890.30541770.25422925310299
3.4989-3.68310.31611630.24982970313399
3.6831-3.91340.29391520.232984313699
3.9134-4.21470.29171500.19812991314199
4.2147-4.63740.19271390.16723003314299
4.6374-5.30510.20251510.168230413192100
5.3051-6.67120.23341620.210430843246100
6.6712-29.59810.20511870.21513181336899
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)
11.52540.6965-0.04970.9229-0.06372.9175-0.0218-0.116-0.146-0.5185-0.0349-0.07490.16690.14650.03650.4083-0.00110.03440.1092-0.03160.208224.21124.5752-31.5154
21.15110.03780.48882.14440.84042.9711-0.30470.10160.1911-0.81580.0554-0.6351-0.30830.38170.15320.6507-0.10070.15740.2130.00230.388334.388423.5384-37.6645
31.91160.5568-0.41211.22690.2042.56750.0914-0.10770.2876-0.1856-0.10520.2097-0.3759-0.0580.01470.41270.0088-0.14670.1449-0.01260.252569.5556-6.2319-32.0136
40.7984-0.2339-0.06271.0063-0.89942.7139-0.32730.141-0.0386-0.63420.03760.62190.0614-0.49030.090.4804-0.0595-0.25110.2784-0.02680.393460.0927-25.6849-37.8348
50.547-0.0328-0.11181.11710.22870.6734-0.41450.633-0.2086-0.92370.2333-0.0049-0.21720.14970.13521.8961-0.26370.23150.4462-0.07310.482531.114711.352-64.6608
60.787-0.07150.11130.5526-0.22870.5557-0.1830.74540.2352-0.54340.0683-0.1657-0.0673-0.04850.06831.6511-0.2328-0.47220.57320.18720.305965.8831-15.6354-65.2084
71.27870.03050.26991.33370.30411.20190.0607-0.5220.17560.01040.03480.13810.1869-0.1728-0.0556-0.16270.0249-0.19590.9017-0.14090.263828.785519.16582.4757
82.78530.15580.14721.483-0.0971.2253-0.0564-0.1739-0.00360.0435-0.0418-0.22310.05930.37150.0732-0.0431-0.024-0.12090.6266-0.27070.459240.843524.1875-8.2923
92.9597-0.22090.14321.4653-0.0771.4845-0.1366-0.36740.17230.0961-0.09340.1498-0.2448-0.39560.067-0.0688-0.00860.07030.6781-0.01860.425351.5856-23.9239-7.6163
101.7880.0398-0.33061.6741-0.41961.36560.0137-0.4194-0.06360.04790.009-0.1311-0.21790.0367-0.03760.0768-0.02110.04190.608-0.06460.369563.6313-19.04992.2589
Refinement TLS group
IDRefine-IDRefine TLS-IDSelection detailsAuth asym-IDAuth seq-ID
1X-RAY DIFFRACTION1(chain 'I' and resid 1 through 107)I1 - 107
2X-RAY DIFFRACTION2(chain 'J' and resid 1 through 119)J1 - 119
3X-RAY DIFFRACTION3(chain 'L' and resid 1 through 107)L1 - 107
4X-RAY DIFFRACTION4(chain 'H' and resid 1 through 119)H1 - 119
5X-RAY DIFFRACTION5(chain 'M' and resid 312 through 502)M312 - 502
6X-RAY DIFFRACTION6(chain 'N' and resid 310 through 501)N310 - 501
7X-RAY DIFFRACTION7(chain 'I' and resid 108 through 211)I108 - 211
8X-RAY DIFFRACTION8(chain 'J' and resid 120 through 218)J120 - 218
9X-RAY DIFFRACTION9(chain 'H' and resid 120 through 218)H120 - 218
10X-RAY DIFFRACTION10(chain 'L' and resid 108 through 212)L108 - 212

+
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://pdbjlvh1.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