[English] 日本語
Yorodumi
- PDB-4rt7: Crystal Structure of FLT3 with a small molecule inhibitor -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 4rt7
TitleCrystal Structure of FLT3 with a small molecule inhibitor
ComponentsReceptor-type tyrosine-protein kinase FLT3
KeywordsTRANSFERASE/TRANSFERASE INHIBITOR / Kinase / TRANSFERASE / TRANSFERASE INHIBITOR / COMPLEX / 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: 3.1 Å
AuthorsZhang, Y. / Zhang, C.
CitationJournal: Cancer Discov / Year: 2015
Title: Characterizing and Overriding the Structural Mechanism of the Quizartinib-Resistant FLT3 "Gatekeeper" F691L Mutation with PLX3397.
Authors: Smith, C.C. / Zhang, C. / Lin, K.C. / Lasater, E.A. / Zhang, Y. / Massi, E. / Damon, L.E. / Pendleton, M. / Bashir, A. / Sebra, R. / Perl, A. / Kasarskis, A. / Shellooe, R. / Tsang, G. / ...Authors: Smith, C.C. / Zhang, C. / Lin, K.C. / Lasater, E.A. / Zhang, Y. / Massi, E. / Damon, L.E. / Pendleton, M. / Bashir, A. / Sebra, R. / Perl, A. / Kasarskis, A. / Shellooe, R. / Tsang, G. / Carias, H. / Powell, B. / Burton, E.A. / Matusow, B. / Zhang, J. / Spevak, W. / Ibrahim, P.N. / Le, M.H. / Hsu, H.H. / Habets, G. / West, B.L. / Bollag, G. / Shah, N.P.
History
DepositionNov 13, 2014Deposition site: RCSB / Processing site: RCSB
Revision 1.0Apr 22, 2015Provider: repository / Type: Initial release
Revision 1.1Jun 17, 2015Group: Database references

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

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


Theoretical massNumber of molelcules
Total (without water)48,7612
Polymers48,2001
Non-polymers5611
Water181
1
A: Receptor-type tyrosine-protein kinase FLT3
hetero molecules

A: Receptor-type tyrosine-protein kinase FLT3
hetero molecules


Theoretical massNumber of molelcules
Total (without water)97,5224
Polymers96,4012
Non-polymers1,1212
Water362
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
crystal symmetry operation6_554-x,-x+y,-z-1/31
Buried area1460 Å2
ΔGint-8 kcal/mol
Surface area24560 Å2
MethodPISA
Unit cell
Length a, b, c (Å)78.880, 78.880, 138.360
Angle α, β, γ (deg.)90.00, 90.00, 120.00
Int Tables number154
Space group name H-MP3221

-
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: 48200.316 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: FLT3, CD135, FLK2, STK1 / Production host: Spodoptera frugiperda (fall armyworm)
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.: 1 / Source method: obtained synthetically / Formula: C29H32N6O4S / Comment: medication, anticancer, inhibitor*YM
#3: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 1 / 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: 2.58 Å3/Da / Density % sol: 52.29 %
Crystal growTemperature: 293 K / Method: vapor diffusion, sitting drop / pH: 5.5
Details: 100mM Na-Citrate, pH5.5 and 20% PEG3000, VAPOR DIFFUSION, SITTING DROP, temperature 293K

-
Data collection

DiffractionMean temperature: 100 K
Diffraction sourceSource: SYNCHROTRON / Site: ALS / Beamline: 8.3.1 / Wavelength: 1.1159 Å
DetectorType: ADSC QUANTUM 210 / Detector: CCD / Date: Mar 25, 2014
RadiationMonochromator: DOUBLE FLAT CRYSTAL, SI(111) / Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1.1159 Å / Relative weight: 1
ReflectionResolution: 3.1→61.253 Å / Num. all: 9504 / Num. obs: 8651 / % possible obs: 91.02 % / Observed criterion σ(F): -3 / Observed criterion σ(I): -3

-
Processing

Software
NameVersionClassification
Blu-Icedata collection
MOLREPphasing
PHENIX(phenix.refine: 1.7.3_928)refinement
MOSFLMdata reduction
SCALAdata scaling
RefinementMethod to determine structure: MOLECULAR REPLACEMENT / Resolution: 3.1→61.253 Å / SU ML: 0.42 / σ(F): 0.07 / Phase error: 24.86 / Stereochemistry target values: MLHL
RfactorNum. reflection% reflectionSelection details
Rfree0.2677 868 10.03 %RANDOM
Rwork0.2185 ---
obs0.2236 8651 91.02 %-
all-9504 --
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT BULK SOLVENT MODEL / Bsol: 26.74 Å2 / ksol: 0.327 e/Å3
Displacement parameters
Baniso -1Baniso -2Baniso -3
1-5.5825 Å2-0 Å2-0 Å2
2--5.5825 Å2-0 Å2
3----11.165 Å2
Refinement stepCycle: LAST / Resolution: 3.1→61.253 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms2180 0 40 1 2221
Refine LS restraints
Refine-IDTypeDev idealNumber
X-RAY DIFFRACTIONf_bond_d0.0052280
X-RAY DIFFRACTIONf_angle_d0.8983082
X-RAY DIFFRACTIONf_dihedral_angle_d14.769821
X-RAY DIFFRACTIONf_chiral_restr0.064328
X-RAY DIFFRACTIONf_plane_restr0.004384
LS refinement shell
Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkRefine-ID% reflection obs (%)
3.1003-3.29450.34261180.28921149X-RAY DIFFRACTION81
3.2945-3.54880.30461420.25721206X-RAY DIFFRACTION87
3.5488-3.90590.26431410.22861285X-RAY DIFFRACTION91
3.9059-4.4710.22541490.19441304X-RAY DIFFRACTION93
4.471-5.63240.23571520.18821375X-RAY DIFFRACTION95
5.6324-61.2650.291660.21351464X-RAY DIFFRACTION97
Refinement TLS params.Method: refined / Origin x: -31.283 Å / Origin y: 11.5004 Å / Origin z: -14.5792 Å
111213212223313233
T0.3954 Å2-0.041 Å2-0.0568 Å2-0.2457 Å20.0147 Å2--0.3161 Å2
L3.7078 °20.6516 °2-2.1659 °2-0.6017 °2-0.2562 °2--3.6208 °2
S0.0955 Å °0.0378 Å °-0.218 Å °0.0905 Å °-0.0915 Å °0.0215 Å °0.3276 Å °-0.1512 Å °-0.0322 Å °
Refinement TLS groupSelection details: chain A

+
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