[English] 日本語
Yorodumi
- PDB-4xuf: Crystal structure of the FLT3 kinase domain bound to the inhibito... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 4xuf
TitleCrystal structure of the FLT3 kinase domain bound to the inhibitor quizartinib (AC220)
ComponentsReceptor-type tyrosine-protein kinase FLT3
KeywordsTransferase/transferase inhibitor / FLT3 / receptor tyrosine kinase / AC220 / quizartinib / Transferase-transferase inhibitor complex
Function / homology
Function and homology information


FLT3 mutants bind TKIs / KW2449-resistant FLT3 mutants / semaxanib-resistant FLT3 mutants / crenolanib-resistant FLT3 mutants / gilteritinib-resistant FLT3 mutants / lestaurtinib-resistant FLT3 mutants / midostaurin-resistant FLT3 mutants / pexidartinib-resistant FLT3 mutants / ponatinib-resistant FLT3 mutants / quizartinib-resistant FLT3 mutants ...FLT3 mutants bind TKIs / KW2449-resistant FLT3 mutants / semaxanib-resistant FLT3 mutants / crenolanib-resistant FLT3 mutants / gilteritinib-resistant FLT3 mutants / lestaurtinib-resistant FLT3 mutants / midostaurin-resistant FLT3 mutants / pexidartinib-resistant FLT3 mutants / ponatinib-resistant FLT3 mutants / quizartinib-resistant FLT3 mutants / sorafenib-resistant FLT3 mutants / sunitinib-resistant FLT3 mutants / tandutinib-resistant FLT3 mutants / linifanib-resistant FLT3 mutants / tamatinib-resistant FLT3 mutants / leukocyte homeostasis / lymphocyte proliferation / pro-B cell differentiation / common myeloid progenitor cell proliferation / dendritic cell differentiation / vascular endothelial growth factor receptor activity / phosphatidylinositol 3-kinase activator activity / STAT5 Activation / nuclear glucocorticoid receptor binding / myeloid progenitor cell differentiation / FLT3 signaling through SRC family kinases / cellular response to glucocorticoid stimulus / cytokine receptor activity / STAT5 activation downstream of FLT3 ITD mutants / growth factor binding / cellular response to cytokine stimulus / hemopoiesis / PI3K Cascade / animal organ regeneration / Signaling by FLT3 ITD and TKD mutants / positive regulation of tyrosine phosphorylation of STAT protein / FLT3 signaling by CBL mutants / cell surface receptor protein tyrosine kinase signaling pathway / : / Negative regulation of FLT3 / FLT3 Signaling / transmembrane receptor protein tyrosine kinase activity / B cell differentiation / positive regulation of MAP kinase activity / receptor protein-tyrosine kinase / cytokine-mediated signaling pathway / peptidyl-tyrosine phosphorylation / Constitutive Signaling by Aberrant PI3K in Cancer / : / PIP3 activates AKT signaling / PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling / RAF/MAP kinase cascade / regulation of apoptotic process / protein tyrosine kinase activity / positive regulation of MAPK cascade / protein autophosphorylation / positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction / receptor complex / endosome membrane / endoplasmic reticulum lumen / positive regulation of cell population proliferation / protein-containing complex binding / endoplasmic reticulum / ATP binding / plasma membrane
Similarity search - Function
Tyrosine-protein kinase, receptor class III, conserved site / Receptor tyrosine kinase class III signature. / Immunoglobulin / Immunoglobulin domain / 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 ...Tyrosine-protein kinase, receptor class III, conserved site / Receptor tyrosine kinase class III signature. / Immunoglobulin / Immunoglobulin domain / 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 / Ig-like domain profile. / Immunoglobulin-like domain / Immunoglobulin-like 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-P30 / Receptor-type tyrosine-protein kinase FLT3
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 3.2 Å
AuthorsZorn, J.A. / Wang, Q. / Fujimura, E. / Barros, T. / Kuriyan, J.
Funding support United States, 3items
OrganizationGrant numberCountry
National Institutes of Health/National Cancer Institute (NIH/NCI)F32 CA177087-02 United States
Cancer Research Institute United States
Howard Hughes Medical Institute (HHMI) United States
CitationJournal: Plos One / Year: 2015
Title: Crystal Structure of the FLT3 Kinase Domain Bound to the Inhibitor Quizartinib (AC220).
Authors: Zorn, J.A. / Wang, Q. / Fujimura, E. / Barros, T. / Kuriyan, J.
History
DepositionJan 25, 2015Deposition site: RCSB / Processing site: RCSB
Revision 1.0Apr 15, 2015Provider: repository / Type: Initial release
Revision 1.1Apr 29, 2015Group: Database references
Revision 1.2Aug 26, 2015Group: Experimental preparation
Revision 1.3Sep 6, 2017Group: Author supporting evidence / Derived calculations / Category: pdbx_audit_support / pdbx_struct_oper_list
Item: _pdbx_audit_support.funding_organization / _pdbx_struct_oper_list.symmetry_operation
Revision 1.4Nov 20, 2019Group: Author supporting evidence / Category: pdbx_audit_support / Item: _pdbx_audit_support.funding_organization
Revision 1.5Sep 27, 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 / struct_ncs_dom_lim
Item: _chem_comp.pdbx_synonyms / _database_2.pdbx_DOI ..._chem_comp.pdbx_synonyms / _database_2.pdbx_DOI / _database_2.pdbx_database_accession / _struct_ncs_dom_lim.beg_auth_comp_id / _struct_ncs_dom_lim.beg_label_asym_id / _struct_ncs_dom_lim.beg_label_comp_id / _struct_ncs_dom_lim.beg_label_seq_id / _struct_ncs_dom_lim.end_auth_comp_id / _struct_ncs_dom_lim.end_label_asym_id / _struct_ncs_dom_lim.end_label_comp_id / _struct_ncs_dom_lim.end_label_seq_id

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Receptor-type tyrosine-protein kinase FLT3
B: Receptor-type tyrosine-protein kinase FLT3
hetero molecules


Theoretical massNumber of molelcules
Total (without water)69,0854
Polymers67,9642
Non-polymers1,1212
Water362
1
A: Receptor-type tyrosine-protein kinase FLT3
hetero molecules


Theoretical massNumber of molelcules
Total (without water)34,5432
Polymers33,9821
Non-polymers5611
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
MethodPISA
2
B: Receptor-type tyrosine-protein kinase FLT3
hetero molecules


Theoretical massNumber of molelcules
Total (without water)34,5432
Polymers33,9821
Non-polymers5611
Water0
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
MethodPISA
Unit cell
Length a, b, c (Å)48.726, 75.492, 153.968
Angle α, β, γ (deg.)90.000, 90.000, 90.000
Int Tables number19
Space group name H-MP212121
Noncrystallographic symmetry (NCS)NCS domain:
IDEns-IDDetails
11chain A
21chain B

NCS domain segments:

Component-ID: 1 / Ens-ID: 1 / Beg auth comp-ID: ASP / Beg label comp-ID: ASP

Dom-IDEnd auth comp-IDEnd label comp-IDSelection detailsAuth asym-IDLabel asym-IDAuth seq-IDLabel seq-ID
1LEULEUchain AAA600 - 9471 - 297
2GLNGLNchain BBB600 - 9461 - 296

-
Components

#1: Protein Receptor-type tyrosine-protein kinase FLT3 / FL cytokine receptor / Fetal liver kinase-2 / FLK-2 / Fms-like tyrosine kinase 3 / FLT-3 / Stem ...FL cytokine receptor / Fetal liver kinase-2 / FLK-2 / Fms-like tyrosine kinase 3 / FLT-3 / Stem cell tyrosine kinase 1 / STK-1


Mass: 33982.051 Da / Num. of mol.: 2 / Fragment: UNP residues 600-710, 762-947 / Mutation: delta(711-761)
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: FLT3, CD135, FLK2, STK1 / Production host: unidentified baculovirus
References: UniProt: P36888, receptor protein-tyrosine kinase
#2: Chemical ChemComp-P30 / 1-(5-tert-butyl-1,2-oxazol-3-yl)-3-(4-{7-[2-(morpholin-4-yl)ethoxy]imidazo[2,1-b][1,3]benzothiazol-2-yl}phenyl)urea / Quizartinib / PLX3397


Mass: 560.667 Da / Num. of mol.: 2
Source method: isolated from a genetically manipulated source
Formula: C29H32N6O4S / Comment: medication, anticancer, inhibitor*YM
#3: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 2 / 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: 2.08 Å3/Da / Density % sol: 40.96 %
Crystal growTemperature: 294 K / Method: vapor diffusion, sitting drop / pH: 7.5 / Details: 0.1 M Tris-HCl, pH 7.5, 32% PEG 3350

-
Data collection

DiffractionMean temperature: 80 K
Diffraction sourceSource: SYNCHROTRON / Site: ALS / Beamline: 8.2.2 / Wavelength: 1 Å
DetectorType: ADSC QUANTUM 315r / Detector: CCD / Date: Sep 10, 2014
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1 Å / Relative weight: 1
ReflectionResolution: 3.2→50 Å / Num. obs: 9403 / % possible obs: 94.3 % / Redundancy: 3.5 % / Biso Wilson estimate: 75.04 Å2 / Rmerge(I) obs: 0.209 / Rpim(I) all: 0.131 / Rrim(I) all: 0.248 / Χ2: 1.219 / Net I/av σ(I): 5.545 / Net I/σ(I): 5.3 / Num. measured all: 32682
Reflection shell

Diffraction-ID: 1 / Rejects: _

Resolution (Å)Redundancy (%)Rmerge(I) obsNum. unique allCC1/2Rpim(I) allRrim(I) allΧ2% possible all
3.2-3.312.90.5977440.6980.390.7171.06177.1
3.31-3.453.10.738740.7410.4840.8811.27988.8
3.45-3.63.30.5548920.7660.3630.6661.22392.3
3.6-3.793.50.3489410.8020.220.4141.45995.2
3.79-4.033.60.3859320.9020.2370.4531.06896.5
4.03-4.343.70.249450.9450.1460.2821.34296.7
4.34-4.783.70.2049610.970.1210.2391.23995.8
4.78-5.473.70.19510070.9640.1180.2291.196100
5.47-6.893.60.16710170.9730.1010.1961.20499.9
6.89-503.50.1210900.980.0780.1441.08799.5

-
Processing

Software
NameVersionClassification
PHENIX(phenix.refine: dev_1839)refinement
HKL-2000data reduction
PDB_EXTRACT3.15data extraction
HKL-2000data scaling
PHENIXphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: PDB entry 1RJB

1rjb


Resolution: 3.2→46.455 Å / SU ML: 0.53 / Cross valid method: FREE R-VALUE / σ(F): 1.33 / Phase error: 38.52 / Stereochemistry target values: ML
RfactorNum. reflection% reflection
Rfree0.3204 932 10.01 %
Rwork0.2968 8378 -
obs0.2992 9310 91.72 %
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT BULK SOLVENT MODEL
Displacement parametersBiso max: 127.74 Å2 / Biso mean: 68.1542 Å2 / Biso min: 45.16 Å2
Refinement stepCycle: final / Resolution: 3.2→46.455 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms4333 0 80 2 4415
Biso mean--64.99 66.72 -
Num. residues----544
Refine LS restraints
Refine-IDTypeDev idealNumber
X-RAY DIFFRACTIONf_bond_d0.0044524
X-RAY DIFFRACTIONf_angle_d0.8746114
X-RAY DIFFRACTIONf_chiral_restr0.041650
X-RAY DIFFRACTIONf_plane_restr0.004761
X-RAY DIFFRACTIONf_dihedral_angle_d13.8411668
Refine LS restraints NCS
Ens-IDDom-IDAuth asym-IDNumberRefine-IDRmsType
11A2286X-RAY DIFFRACTION9.555TORSIONAL
12B2286X-RAY DIFFRACTION9.555TORSIONAL
LS refinement shell

Refine-ID: X-RAY DIFFRACTION / Total num. of bins used: 7

Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkNum. reflection all% reflection obs (%)
3.2-3.34030.3884950.367484594066
3.3403-3.54950.40141280.36421137126590
3.5495-3.82340.40461350.34291225136094
3.8234-4.2080.34851350.3031223135895
4.208-4.81630.31391400.28791256139696
4.8163-6.06590.26251460.300613051451100
6.0659-46.46020.26981530.24691387154099

+
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