[English] 日本語
Yorodumi
- PDB-7zv9: Crystal structure of FLT3 in complex with a monomeric FLT3 Ligand... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 7zv9
TitleCrystal structure of FLT3 in complex with a monomeric FLT3 Ligand variant
Components
  • Fms-related tyrosine kinase 3 ligand
  • Receptor-type tyrosine-protein kinase FLT3
KeywordsSIGNALING PROTEIN / Inactive complex / Complex / Receptor Tyrosine Kinase / RTK-III
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 / common myeloid progenitor cell proliferation / pro-B cell differentiation / lymphocyte proliferation / vascular endothelial growth factor receptor activity / dendritic cell differentiation / nuclear glucocorticoid receptor binding / STAT5 Activation / phosphatidylinositol 3-kinase activator activity / FLT3 signaling through SRC family kinases / myeloid progenitor cell differentiation / cytokine receptor activity / embryonic hemopoiesis / positive regulation of tyrosine phosphorylation of STAT protein / cellular response to glucocorticoid stimulus / growth factor binding / STAT5 activation downstream of FLT3 ITD mutants / cellular response to cytokine stimulus / positive regulation of MAP kinase activity / positive regulation of natural killer cell proliferation / hemopoiesis / PI3K Cascade / Signaling by FLT3 ITD and TKD mutants / FLT3 signaling by CBL mutants / liver regeneration / FLT3 Signaling / transmembrane receptor protein tyrosine kinase activity / Negative regulation of FLT3 / cell surface receptor protein tyrosine kinase signaling pathway / peptidyl-tyrosine phosphorylation / B cell differentiation / cytokine activity / receptor protein-tyrosine kinase / receptor tyrosine kinase binding / cytokine-mediated signaling pathway / Constitutive Signaling by Aberrant PI3K in Cancer / cell migration / PIP3 activates AKT signaling / protein autophosphorylation / PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling / RAF/MAP kinase cascade / protein tyrosine kinase activity / regulation of apoptotic process / positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction / receptor complex / positive regulation of MAPK cascade / endosome membrane / endoplasmic reticulum lumen / signaling receptor binding / positive regulation of cell population proliferation / protein-containing complex binding / cell surface / endoplasmic reticulum / signal transduction / extracellular space / extracellular region / ATP binding / membrane / plasma membrane / cytosol
Similarity search - Function
Flt3 ligand / flt3 ligand / Tyrosine-protein kinase, receptor class III, conserved site / Receptor tyrosine kinase class III signature. / Four-helical cytokine-like, core / Immunoglobulin / Immunoglobulin domain / : / Tyrosine-protein kinase, catalytic domain / Tyrosine kinase, catalytic domain ...Flt3 ligand / flt3 ligand / Tyrosine-protein kinase, receptor class III, conserved site / Receptor tyrosine kinase class III signature. / Four-helical cytokine-like, core / Immunoglobulin / Immunoglobulin domain / : / 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 / 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
Similarity search - Domain/homology
Receptor-type tyrosine-protein kinase FLT3 / Fms-related tyrosine kinase 3 ligand
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 4.507 Å
AuthorsPannecoucke, E. / Savvides, S.N.
Funding support Belgium, 1items
OrganizationGrant numberCountry
Research Foundation - Flanders (FWO) Belgium
CitationJournal: To Be Published
Title: Crystal structure of FLT3 in complex with a monomeric FLT3 Ligand variant
Authors: Pannecoucke, E. / Savvides, S.N.
History
DepositionMay 14, 2022Deposition site: PDBE / Processing site: PDBE
Revision 1.0May 31, 2023Provider: repository / Type: Initial release
Revision 1.1Feb 7, 2024Group: Data collection / Refinement description
Category: chem_comp_atom / chem_comp_bond / pdbx_initial_refinement_model
Revision 1.2Oct 23, 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: Fms-related tyrosine kinase 3 ligand
B: Receptor-type tyrosine-protein kinase FLT3
C: Fms-related tyrosine kinase 3 ligand
D: Receptor-type tyrosine-protein kinase FLT3
E: Fms-related tyrosine kinase 3 ligand
F: Receptor-type tyrosine-protein kinase FLT3
G: Fms-related tyrosine kinase 3 ligand
H: Receptor-type tyrosine-protein kinase FLT3
I: Fms-related tyrosine kinase 3 ligand
J: Receptor-type tyrosine-protein kinase FLT3
K: Fms-related tyrosine kinase 3 ligand
L: Receptor-type tyrosine-protein kinase FLT3
M: Fms-related tyrosine kinase 3 ligand
N: Receptor-type tyrosine-protein kinase FLT3
O: Fms-related tyrosine kinase 3 ligand
P: Receptor-type tyrosine-protein kinase FLT3
hetero molecules


Theoretical massNumber of molelcules
Total (without water)668,00826
Polymers664,57716
Non-polymers3,43110
Water00
1
A: Fms-related tyrosine kinase 3 ligand
B: Receptor-type tyrosine-protein kinase FLT3
hetero molecules


Theoretical massNumber of molelcules
Total (without water)83,5144
Polymers83,0722
Non-polymers4422
Water0
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
2
C: Fms-related tyrosine kinase 3 ligand
D: Receptor-type tyrosine-protein kinase FLT3
hetero molecules


Theoretical massNumber of molelcules
Total (without water)83,4963
Polymers83,0722
Non-polymers4241
Water0
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
3
E: Fms-related tyrosine kinase 3 ligand
F: Receptor-type tyrosine-protein kinase FLT3
hetero molecules


Theoretical massNumber of molelcules
Total (without water)83,4963
Polymers83,0722
Non-polymers4241
Water0
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
4
G: Fms-related tyrosine kinase 3 ligand
H: Receptor-type tyrosine-protein kinase FLT3
hetero molecules


Theoretical massNumber of molelcules
Total (without water)83,2933
Polymers83,0722
Non-polymers2211
Water0
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
5
I: Fms-related tyrosine kinase 3 ligand
J: Receptor-type tyrosine-protein kinase FLT3
hetero molecules


Theoretical massNumber of molelcules
Total (without water)83,4963
Polymers83,0722
Non-polymers4241
Water0
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
6
K: Fms-related tyrosine kinase 3 ligand
L: Receptor-type tyrosine-protein kinase FLT3
hetero molecules


Theoretical massNumber of molelcules
Total (without water)83,4963
Polymers83,0722
Non-polymers4241
Water0
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
7
M: Fms-related tyrosine kinase 3 ligand
N: Receptor-type tyrosine-protein kinase FLT3
hetero molecules


Theoretical massNumber of molelcules
Total (without water)83,4963
Polymers83,0722
Non-polymers4241
Water0
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
8
O: Fms-related tyrosine kinase 3 ligand
P: Receptor-type tyrosine-protein kinase FLT3
hetero molecules


Theoretical massNumber of molelcules
Total (without water)83,7184
Polymers83,0722
Non-polymers6462
Water0
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Unit cell
Length a, b, c (Å)139.208, 139.215, 143.689
Angle α, β, γ (deg.)90.02, 90.03, 89.99
Int Tables number1
Space group name H-MP1

-
Components

#1: Protein
Fms-related tyrosine kinase 3 ligand / Flt3 ligand / Flt3L / SL cytokine


Mass: 17764.242 Da / Num. of mol.: 8 / Mutation: L27D
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: FLT3LG / Production host: Escherichia coli BL21(DE3) (bacteria) / References: UniProt: P49771
#2: 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: 65307.824 Da / Num. of mol.: 8
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: FLT3, CD135, FLK2, STK1 / Plasmid: pcDNA4/TO / Production host: Homo sapiens (human) / Strain (production host): Human embryonic kidney 293 / Variant (production host): MGAT-/- TR+
References: UniProt: P36888, receptor protein-tyrosine kinase
#3: Polysaccharide
2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose


Type: oligosaccharide / Mass: 424.401 Da / Num. of mol.: 6
Source method: isolated from a genetically manipulated source
DescriptorTypeProgram
DGlcpNAcb1-4DGlcpNAcb1-ROHGlycam Condensed SequenceGMML 1.0
WURCS=2.0/1,2,1/[a2122h-1b_1-5_2*NCC/3=O]/1-1/a4-b1WURCSPDB2Glycan 1.1.0
[][D-1-deoxy-GlcpNAc]{[(4+1)][b-D-GlcpNAc]{}}LINUCSPDB-CARE
#4: 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.: 4 / Source method: obtained synthetically / 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
Has ligand of interestN
Has protein modificationY

-
Experimental details

-
Experiment

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

-
Sample preparation

CrystalDensity Matthews: 4.19 Å3/Da / Density % sol: 70.67 %
Crystal growTemperature: 293 K / Method: vapor diffusion, sitting drop / pH: 8.3
Details: 0.9 M ammonium sulfate 10% PEG 8000 MES buffer pH 8.3

-
Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: SLS / Beamline: X06DA / Wavelength: 1 Å
DetectorType: DECTRIS PILATUS 2M-F / Detector: PIXEL / Date: Oct 25, 2017
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1 Å / Relative weight: 1
ReflectionResolution: 4.3→50 Å / Num. obs: 68007 / % possible obs: 92.3 % / Redundancy: 1.68 % / CC1/2: 0.998 / Net I/σ(I): 7.64
Reflection shellResolution: 4.3→4.6 Å / Redundancy: 1.66 % / Mean I/σ(I) obs: 0.44 / Num. unique obs: 1187 / CC1/2: 0.222 / % possible all: 93

-
Processing

Software
NameVersionClassification
BUSTER2.10.3refinement
PHENIX1.20-4459refinement
XDSdata scaling
PHASERphasing
Cootmodel building
PDB-REDOrefinement
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 3QS7

3qs7


Resolution: 4.507→47.9 Å / Cor.coef. Fo:Fc: 0.841 / Cor.coef. Fo:Fc free: 0.792 / Cross valid method: THROUGHOUT / SU Rfree Blow DPI: 1.136
RfactorNum. reflection% reflectionSelection details
Rfree0.2913 2027 -RANDOM
Rwork0.2777 ---
obs0.2784 42090 66.2 %-
Displacement parametersBiso mean: 200.99 Å2
Baniso -1Baniso -2Baniso -3
1--1.9395 Å25.463 Å2-10.0354 Å2
2---9.1462 Å20.657 Å2
3---11.0857 Å2
Refine analyzeLuzzati coordinate error obs: 1.01 Å
Refinement stepCycle: LAST / Resolution: 4.507→47.9 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms26467 0 224 0 26691
Refine LS restraints
Refine-IDTypeDev idealNumberRestraint functionWeight
X-RAY DIFFRACTIONt_bond_d0.00527132HARMONIC2
X-RAY DIFFRACTIONt_angle_deg0.8337588HARMONIC2
X-RAY DIFFRACTIONt_dihedral_angle_d6770SINUSOIDAL2
X-RAY DIFFRACTIONt_gen_planes4917HARMONIC5
X-RAY DIFFRACTIONt_it26892HARMONIC10
X-RAY DIFFRACTIONt_chiral_improper_torsion4555SEMIHARMONIC5
X-RAY DIFFRACTIONt_ideal_dist_contact14098SEMIHARMONIC4
X-RAY DIFFRACTIONt_omega_torsion5.61
X-RAY DIFFRACTIONt_other_torsion21.37
LS refinement shellResolution: 4.51→4.64 Å
RfactorNum. reflection% reflection
Rfree0.3118 32 -
Rwork0.2067 --
obs0.2114 842 15.7 %
Refinement TLS params.

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)
18.50644.9421-2.02174.22990.55014.8870.20920.0687-0.07620.0687-0.385-0.9412-0.0762-0.94120.17580.2210.2172-0.3040.60780.05620.3467-117.3807-54.351971.4293
216.62742.42394.203112.2065-0.361216.63490.1330.7782-1.08820.77820.1327-1.0885-1.0882-1.0885-0.2657-0.00960.1574-0.2037-0.36160.01580.6077-68.7438-36.631232.1762
316.6348-0.5547-4.050112.72862.053816.6280.0623-0.59330.316-0.5933-0.3856-1.04540.316-1.04540.32330.0329-0.0131-0.0003-0.2927-0.16720.6078-68.674-97.67873.4088
45.6467-4.0566-1.07993.4444-0.80914.88390.0122-0.2719-0.3521-0.2719-0.31621.058-0.35211.0580.30410.15-0.1371-0.27840.60790.14710.5519-14.9145-53.931336.0178
57.94284.79312.93654.0774-0.85596.4382-0.14220.15460.37340.1546-0.21311.0880.37341.0880.3553-0.00010.13370.12270.60770.27180.5764-15.2288-80.3029-0.7681
614.11361.69592.973215.37-5.820816.63050.1073-0.79311.0883-0.7931-0.3070.71181.08830.71180.1998-0.29880.14540.0183-0.11160.20180.6081-35.5807-69.9578-32.762
73.8152-3.57720.17347.33431.85334.5828-0.17250.4674-1.08850.4674-0.06150.1857-1.08850.18570.2340.6082-0.1962-0.30390.27910.21980.3702-53.0697-16.0663-36.6832
811.2486-0.5217-1.303916.62765.820816.6330.585-1.0424-1.0885-1.0424-0.2057-0.9393-1.0885-0.9393-0.3793-0.19410.1591-0.30430.0299-00.6076-96.6902-64.608938.9437
92.0612-3.6658-0.11736.1011-1.34875.43750.18451.06610.83721.0661-0.52180.13210.83720.13210.33740.6078-0.26380.01830.089-0.1190.4531-78.9028-118.396135.1541
1011.97370.3673-2.130216.6342-5.820316.62530.36621.0886-1.0881.0886-0.64270.8487-1.0880.84870.2765-0.410.07-0.15820.16030.16270.5966-35.625-64.409968.118
113.54133.3951-0.08712.04692.93133.3196-0.11450.25331.08860.25330.20810.34791.08860.3479-0.09360.6080.2474-0.03890.21260.18110.4449-53.2123-118.64171.9764
1216.635-5.8202-5.822511.54470.559616.6253-0.48451.08851.08871.08850.53770.88051.08870.8805-0.0532-0.0403-0.0495-0.0612-0.21760.05160.6079-63.5959-97.6548-39.7585
1310.4567-4.65763.60414.99380.02615.4482-0.0084-0.00270.1661-0.0027-0.229-1.08880.1661-1.08880.23740.0425-0.22330.1690.608-0.06870.2995-117.5024-80.0149-35.8578
1415.5516-2.806-2.670415.93455.819616.6317-0.00261.05221.08891.05220.3492-0.72411.0889-0.7241-0.3466-0.1491-0.06220.0888-0.1105-0.00030.593-96.4097-70.1515-3.4446
155.09675.241-1.31410.1175-4.93387.7239-0.1737-0.4083-1.0085-0.4083-0.14950.1138-1.00850.11380.32320.60820.091-0.25520.0634-0.14650.0239-79.1803-16.2034-0.3407
1615.72974.53145.821713.39190.258316.6369-0.4959-0.5413-0.9381-0.54130.59171.0894-0.93811.0894-0.0958-0.19850.0628-0.1917-0.31590.12760.6052-63.3061-36.86474.9481
Refinement TLS group
IDRefine-IDRefine TLS-IDSelection details
1X-RAY DIFFRACTION1{ N|* }
2X-RAY DIFFRACTION2{ A|* }
3X-RAY DIFFRACTION3{ O|* }
4X-RAY DIFFRACTION4{ B|* }
5X-RAY DIFFRACTION5{ P|* }
6X-RAY DIFFRACTION6{ C|* }
7X-RAY DIFFRACTION7{ D|* }
8X-RAY DIFFRACTION8{ E|* }
9X-RAY DIFFRACTION9{ F|* }
10X-RAY DIFFRACTION10{ G|* }
11X-RAY DIFFRACTION11{ H|* }
12X-RAY DIFFRACTION12{ I|* }
13X-RAY DIFFRACTION13{ J|* }
14X-RAY DIFFRACTION14{ K|* }
15X-RAY DIFFRACTION15{ L|* }
16X-RAY DIFFRACTION16{ M|* }

+
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