[English] 日本語
Yorodumi
- PDB-2x2k: Crystal Structure of phosphorylated RET tyrosine kinase domain wi... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 2x2k
TitleCrystal Structure of phosphorylated RET tyrosine kinase domain with inhibitor
ComponentsPROTO-ONCOGENE TYROSINE-PROTEIN KINASE RECEPTOR RET
KeywordsTRANSFERASE / TYROSINE KINASE / HIRSCHSPRUNG DISEASE / TYROSINE-PROTEIN KINASE / PROTO-ONCOGENE / PHOSPHOPROTEIN / PHOSPHOTRANSFERASE
Function / homology
Function and homology information


Peyer's patch morphogenesis / GDF15-GFRAL signaling pathway / positive regulation of metanephric glomerulus development / ureter maturation / embryonic epithelial tube formation / glial cell-derived neurotrophic factor receptor signaling pathway / lymphocyte migration into lymphoid organs / posterior midgut development / Formation of the ureteric bud / membrane protein proteolysis ...Peyer's patch morphogenesis / GDF15-GFRAL signaling pathway / positive regulation of metanephric glomerulus development / ureter maturation / embryonic epithelial tube formation / glial cell-derived neurotrophic factor receptor signaling pathway / lymphocyte migration into lymphoid organs / posterior midgut development / Formation of the ureteric bud / membrane protein proteolysis / Formation of the nephric duct / enteric nervous system development / neuron cell-cell adhesion / plasma membrane protein complex / neuron maturation / positive regulation of extrinsic apoptotic signaling pathway in absence of ligand / positive regulation of cell adhesion mediated by integrin / neural crest cell migration / ureteric bud development / response to pain / regulation of axonogenesis / homophilic cell-cell adhesion / RET signaling / positive regulation of cell size / regulation of cell adhesion / cellular response to retinoic acid / NPAS4 regulates expression of target genes / transmembrane receptor protein tyrosine kinase activity / axon guidance / cell surface receptor protein tyrosine kinase signaling pathway / positive regulation of neuron projection development / receptor protein-tyrosine kinase / MAPK cascade / signaling receptor activity / RAF/MAP kinase cascade / protein tyrosine kinase activity / positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction / receptor complex / endosome membrane / positive regulation of MAPK cascade / positive regulation of cell migration / axon / calcium ion binding / positive regulation of gene expression / positive regulation of DNA-templated transcription / signal transduction / ATP binding / plasma membrane
Similarity search - Function
Tyrosine-protein kinase, Ret receptor / Tyrosine-protein kinase receptor Ret, cadherin like domain 3 / Ret, cadherin like domain 1 / RET, cadherin-like domain 4 / : / RET Cadherin like domain 1 / RET Cadherin like domain 3 / RET Cadherin like domain 4 / RET, Cysteine Rich Domain / Cadherin domain ...Tyrosine-protein kinase, Ret receptor / Tyrosine-protein kinase receptor Ret, cadherin like domain 3 / Ret, cadherin like domain 1 / RET, cadherin-like domain 4 / : / RET Cadherin like domain 1 / RET Cadherin like domain 3 / RET Cadherin like domain 4 / RET, Cysteine Rich Domain / Cadherin domain / Cadherin-like / Cadherins domain profile. / Cadherin-like superfamily / : / Tyrosine-protein kinase, catalytic domain / Tyrosine kinase, catalytic domain / 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 / Phosphorylase Kinase; domain 1 / Phosphorylase Kinase; domain 1 / Transferase(Phosphotransferase) domain 1 / Transferase(Phosphotransferase); domain 1 / Protein kinase, ATP binding site / Protein kinases ATP-binding region signature. / 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
FORMIC ACID / Chem-X2K / Proto-oncogene tyrosine-protein kinase receptor Ret
Similarity search - Component
Biological speciesHOMO SAPIENS (human)
MethodX-RAY DIFFRACTION / MOLECULAR REPLACEMENT / Resolution: 2.6 Å
AuthorsKnowles, P.P. / Murray-Rust, J. / Kjaer, S. / McDonald, N.Q.
CitationJournal: Bioorg. Med. Chem. / Year: 2010
Title: Synthesis, structure-activity relationship and crystallographic studies of 3-substituted indolin-2-one RET inhibitors.
Authors: Mologni, L. / Rostagno, R. / Brussolo, S. / Knowles, P.P. / Kjaer, S. / Murray-Rust, J. / Rosso, E. / Zambon, A. / Scapozza, L. / McDonald, N.Q. / Lucchini, V. / Gambacorti-Passerini, C.
History
DepositionJan 13, 2010Deposition site: PDBE / Processing site: PDBE
Revision 1.0Feb 9, 2010Provider: repository / Type: Initial release
Revision 1.1Jun 28, 2017Group: Data collection / Category: diffrn_source / Item: _diffrn_source.type
Revision 1.2Apr 18, 2018Group: Data collection / Database references / Category: citation / citation_author
Item: _citation.journal_abbrev / _citation.journal_id_ISSN ..._citation.journal_abbrev / _citation.journal_id_ISSN / _citation.page_last / _citation.pdbx_database_id_DOI / _citation.title / _citation_author.name
Revision 1.3Jan 30, 2019Group: Data collection / Experimental preparation / Category: exptl_crystal_grow / Item: _exptl_crystal_grow.method
Revision 1.4May 8, 2019Group: Data collection / Derived calculations / Experimental preparation
Category: exptl_crystal_grow / struct_conn
Item: _exptl_crystal_grow.temp / _struct_conn.pdbx_leaving_atom_flag
Revision 1.5Dec 20, 2023Group: Data collection / Database references ...Data collection / Database references / Derived calculations / Other / Refinement description
Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / database_2 / pdbx_database_status / pdbx_initial_refinement_model / struct_site
Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession ..._database_2.pdbx_DOI / _database_2.pdbx_database_accession / _pdbx_database_status.status_code_sf / _struct_site.pdbx_auth_asym_id / _struct_site.pdbx_auth_comp_id / _struct_site.pdbx_auth_seq_id
Revision 1.6Nov 13, 2024Group: Structure summary / Category: pdbx_entry_details / pdbx_modification_feature / Item: _pdbx_entry_details.has_protein_modification

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: PROTO-ONCOGENE TYROSINE-PROTEIN KINASE RECEPTOR RET
hetero molecules


Theoretical massNumber of molelcules
Total (without water)36,1805
Polymers35,7881
Non-polymers3914
Water50428
1
A: PROTO-ONCOGENE TYROSINE-PROTEIN KINASE RECEPTOR RET
hetero molecules

A: PROTO-ONCOGENE TYROSINE-PROTEIN KINASE RECEPTOR RET
hetero molecules


Theoretical massNumber of molelcules
Total (without water)72,35910
Polymers71,5762
Non-polymers7838
Water362
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
crystal symmetry operation2_555-x,y,-z1
Buried area4050 Å2
ΔGint-19 kcal/mol
Surface area24150 Å2
MethodPISA
Unit cell
Length a, b, c (Å)71.600, 70.912, 78.871
Angle α, β, γ (deg.)90.00, 101.68, 90.00
Int Tables number5
Space group name H-MC121

-
Components

#1: Protein PROTO-ONCOGENE TYROSINE-PROTEIN KINASE RECEPTOR RET / C-RET


Mass: 35788.215 Da / Num. of mol.: 1 / Fragment: TYROSINE KINASE DOMAIN, RESIDUES 705-1013
Source method: isolated from a genetically manipulated source
Details: RESIDUES 705-1013,5 N-TERMINAL VECTOR-DERIVED RESIDUES GPLSL
Source: (gene. exp.) HOMO SAPIENS (human) / Plasmid: PBACPAK-HIS3 (CLONTECH) MODIFIED / Cell line (production host): SF9 / Production host: SPODOPTERA FRUGIPERDA (fall armyworm)
References: UniProt: P07949, receptor protein-tyrosine kinase
#2: Chemical ChemComp-FMT / FORMIC ACID


Mass: 46.025 Da / Num. of mol.: 3 / Source method: obtained synthetically / Formula: CH2O2
#3: Chemical ChemComp-X2K / (3Z)-5-amino-3-[(3,5-dimethyl-1H-pyrrol-2-yl)methylidene]-1,3-dihydro-2H-indol-2-one


Mass: 253.299 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C15H15N3O
#4: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 28 / Source method: isolated from a natural source / Formula: H2O
Has protein modificationY
Sequence details705-1013 CORRESPOND WITH P07949, 700-704 ARE VECTOR- DERIVED

-
Experimental details

-
Experiment

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

-
Sample preparation

CrystalDensity Matthews: 2.9 Å3/Da / Density % sol: 57.7 % / Description: NONE
Crystal growTemperature: 289 K / Method: vapor diffusion, sitting drop
Details: PROTEIN 4.5 MG/ML IN 20 MM TRIS-HCL PH 8, 100MM NACL,1MM DTT, 1MM EDTA RESERVOIR 1.85 M SODIUM FORMATE, 0.1 SODIUM CITRATE PH 5.5, 0.2M LITHIUM CHLORIDE VAPOUR DIFFUSION, SITTING DROP, 289 K

-
Data collection

DiffractionMean temperature: 100 K
Diffraction sourceSource: ROTATING ANODE / Type: RIGAKU MICROMAX-007 HF / Wavelength: 1.5418
DetectorType: MARRESEARCH / Detector: IMAGE PLATE / Date: Jul 29, 2007 / Details: MIRRORS
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1.5418 Å / Relative weight: 1
ReflectionResolution: 2.6→21.64 Å / Num. obs: 11886 / % possible obs: 99.1 % / Observed criterion σ(I): 0 / Redundancy: 3.1 % / Rmerge(I) obs: 0.06 / Net I/σ(I): 17
Reflection shellResolution: 2.6→2.74 Å / Redundancy: 3 % / Rmerge(I) obs: 0.23 / Mean I/σ(I) obs: 5.2 / % possible all: 100

-
Processing

Software
NameVersionClassification
REFMAC5.2.0019refinement
MOSFLMdata reduction
SCALAdata scaling
MOLREPphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: PDB ENTRY 2IVT, FLEXIBLE LOOPS REMOVED

2ivt


Resolution: 2.6→30 Å / Cor.coef. Fo:Fc: 0.936 / Cor.coef. Fo:Fc free: 0.884 / SU B: 10.037 / SU ML: 0.216 / Cross valid method: THROUGHOUT / ESU R: 0.524 / ESU R Free: 0.306 / Stereochemistry target values: MAXIMUM LIKELIHOOD / Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS
RfactorNum. reflection% reflectionSelection details
Rfree0.256 569 4.8 %RANDOM
Rwork0.191 ---
obs0.194 11316 98.9 %-
Solvent computationIon probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.2 Å / Solvent model: BABINET MODEL WITH MASK
Displacement parametersBiso mean: 39.5 Å2
Baniso -1Baniso -2Baniso -3
1-0.04 Å20 Å20.32 Å2
2--0.69 Å20 Å2
3----0.6 Å2
Refinement stepCycle: LAST / Resolution: 2.6→30 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms2234 0 28 28 2290
Refine LS restraints
Refine-IDTypeDev idealDev ideal targetNumber
X-RAY DIFFRACTIONr_bond_refined_d0.0160.0222317
X-RAY DIFFRACTIONr_bond_other_d
X-RAY DIFFRACTIONr_angle_refined_deg1.6321.9823131
X-RAY DIFFRACTIONr_angle_other_deg
X-RAY DIFFRACTIONr_dihedral_angle_1_deg5.3755289
X-RAY DIFFRACTIONr_dihedral_angle_2_deg35.20123.21887
X-RAY DIFFRACTIONr_dihedral_angle_3_deg16.32515395
X-RAY DIFFRACTIONr_dihedral_angle_4_deg22.4241513
X-RAY DIFFRACTIONr_chiral_restr0.0990.2346
X-RAY DIFFRACTIONr_gen_planes_refined0.0050.021697
X-RAY DIFFRACTIONr_gen_planes_other
X-RAY DIFFRACTIONr_nbd_refined0.2050.2993
X-RAY DIFFRACTIONr_nbd_other
X-RAY DIFFRACTIONr_nbtor_refined0.3050.21551
X-RAY DIFFRACTIONr_nbtor_other
X-RAY DIFFRACTIONr_xyhbond_nbd_refined0.1040.273
X-RAY DIFFRACTIONr_xyhbond_nbd_other
X-RAY DIFFRACTIONr_metal_ion_refined
X-RAY DIFFRACTIONr_metal_ion_other
X-RAY DIFFRACTIONr_symmetry_vdw_refined0.1960.249
X-RAY DIFFRACTIONr_symmetry_vdw_other
X-RAY DIFFRACTIONr_symmetry_hbond_refined0.0430.24
X-RAY DIFFRACTIONr_symmetry_hbond_other
X-RAY DIFFRACTIONr_symmetry_metal_ion_refined
X-RAY DIFFRACTIONr_symmetry_metal_ion_other
X-RAY DIFFRACTIONr_mcbond_it0.7741.51490
X-RAY DIFFRACTIONr_mcbond_other
X-RAY DIFFRACTIONr_mcangle_it1.38722306
X-RAY DIFFRACTIONr_mcangle_other
X-RAY DIFFRACTIONr_scbond_it1.8253978
X-RAY DIFFRACTIONr_scbond_other
X-RAY DIFFRACTIONr_scangle_it2.8714.5824
X-RAY DIFFRACTIONr_scangle_other
X-RAY DIFFRACTIONr_long_range_B_refined
X-RAY DIFFRACTIONr_long_range_B_other
X-RAY DIFFRACTIONr_rigid_bond_restr
X-RAY DIFFRACTIONr_sphericity_free
X-RAY DIFFRACTIONr_sphericity_bonded
LS refinement shellResolution: 2.6→2.67 Å / Total num. of bins used: 20
RfactorNum. reflection% reflection
Rfree0.359 45 -
Rwork0.27 856 -
obs--100 %

+
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