[English] 日本語
Yorodumi
- PDB-6itv: Crystal structure of activated c-KIT in complex with compound -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 6itv
TitleCrystal structure of activated c-KIT in complex with compound
ComponentsMast/stem cell growth factor receptor Kit
KeywordsONCOPROTEIN / Receptor tyrosine kinase DFG motif conformational control inhibitor
Function / homology
Function and homology information


Dasatinib-resistant KIT mutants / Imatinib-resistant KIT mutants / KIT mutants bind TKIs / Masitinib-resistant KIT mutants / Nilotinib-resistant KIT mutants / Regorafenib-resistant KIT mutants / Signaling by kinase domain mutants of KIT / Sunitinib-resistant KIT mutants / Signaling by juxtamembrane domain KIT mutants / Sorafenib-resistant KIT mutants ...Dasatinib-resistant KIT mutants / Imatinib-resistant KIT mutants / KIT mutants bind TKIs / Masitinib-resistant KIT mutants / Nilotinib-resistant KIT mutants / Regorafenib-resistant KIT mutants / Signaling by kinase domain mutants of KIT / Sunitinib-resistant KIT mutants / Signaling by juxtamembrane domain KIT mutants / Sorafenib-resistant KIT mutants / Signaling by extracellular domain mutants of KIT / hematopoietic stem cell migration / melanocyte adhesion / positive regulation of pyloric antrum smooth muscle contraction / positive regulation of colon smooth muscle contraction / positive regulation of vascular associated smooth muscle cell differentiation / melanocyte migration / Kit signaling pathway / positive regulation of small intestine smooth muscle contraction / regulation of bile acid metabolic process / positive regulation of dendritic cell cytokine production / positive regulation of mast cell proliferation / mast cell differentiation / mast cell chemotaxis / Fc receptor signaling pathway / glycosphingolipid metabolic process / mast cell proliferation / positive regulation of long-term neuronal synaptic plasticity / detection of mechanical stimulus involved in sensory perception of sound / positive regulation of pseudopodium assembly / immature B cell differentiation / positive regulation of mast cell cytokine production / lymphoid progenitor cell differentiation / melanocyte differentiation / germ cell migration / erythropoietin-mediated signaling pathway / myeloid progenitor cell differentiation / digestive tract development / negative regulation of programmed cell death / lamellipodium assembly / embryonic hemopoiesis / tongue development / positive regulation of tyrosine phosphorylation of STAT protein / Regulation of KIT signaling / megakaryocyte development / mast cell degranulation / pigmentation / stem cell population maintenance / positive regulation of Notch signaling pathway / growth factor binding / cytokine binding / spermatid development / negative regulation of reproductive process / negative regulation of developmental process / hemopoiesis / somatic stem cell population maintenance / T cell differentiation / ectopic germ cell programmed cell death / hematopoietic progenitor cell differentiation / response to cadmium ion / ovarian follicle development / transmembrane receptor protein tyrosine kinase activity / TFAP2 (AP-2) family regulates transcription of growth factors and their receptors / Transcriptional and post-translational regulation of MITF-M expression and activity / B cell differentiation / SH2 domain binding / Signaling by phosphorylated juxtamembrane, extracellular and kinase domain KIT mutants / acrosomal vesicle / erythrocyte differentiation / positive regulation of DNA-binding transcription factor activity / epithelial cell proliferation / cell chemotaxis / positive regulation of receptor signaling pathway via JAK-STAT / stem cell differentiation / placental growth factor receptor activity / Signaling by SCF-KIT / insulin receptor activity / vascular endothelial growth factor receptor activity / hepatocyte growth factor receptor activity / macrophage colony-stimulating factor receptor activity / platelet-derived growth factor alpha-receptor activity / platelet-derived growth factor beta-receptor activity / stem cell factor receptor activity / boss receptor activity / protein tyrosine kinase collagen receptor activity / brain-derived neurotrophic factor receptor activity / transmembrane-ephrin receptor activity / GPI-linked ephrin receptor activity / epidermal growth factor receptor activity / fibroblast growth factor receptor activity / cytokine-mediated signaling pathway / insulin-like growth factor receptor activity / receptor protein-tyrosine kinase / visual learning / cytoplasmic side of plasma membrane / fibrillar center / male gonad development / Constitutive Signaling by Aberrant PI3K in Cancer / cell-cell junction / cell migration
Similarity search - Function
Mast/stem cell growth factor receptor / Tyrosine-protein kinase, receptor class III, conserved site / Receptor tyrosine kinase class III signature. / Immunoglobulin / Immunoglobulin domain / : / Immunoglobulin subtype 2 / Immunoglobulin C-2 Type / Tyrosine-protein kinase, catalytic domain / Tyrosine kinase, catalytic domain ...Mast/stem cell growth factor receptor / Tyrosine-protein kinase, receptor class III, conserved site / Receptor tyrosine kinase class III signature. / Immunoglobulin / Immunoglobulin domain / : / Immunoglobulin subtype 2 / Immunoglobulin C-2 Type / Tyrosine-protein kinase, catalytic domain / Tyrosine kinase, catalytic domain / Tyrosine protein kinases specific active-site signature. / Tyrosine-protein kinase, active site / Immunoglobulin subtype / Immunoglobulin / Serine-threonine/tyrosine-protein kinase, catalytic domain / Protein tyrosine and serine/threonine kinase / Phosphorylase Kinase; domain 1 / Ig-like domain profile. / Immunoglobulin-like domain / Phosphorylase Kinase; domain 1 / Transferase(Phosphotransferase) domain 1 / Immunoglobulin-like domain superfamily / Transferase(Phosphotransferase); domain 1 / 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-AWO / Mast/stem cell growth factor receptor Kit
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / Resolution: 1.881 Å
AuthorsWu, T.S. / Wu, S.Y.
CitationJournal: To Be Published
Title: Crystal structure of activated c-KIT in complex with compound
Authors: Wu, T.S. / Wu, S.Y.
History
DepositionNov 26, 2018Deposition site: PDBJ / Processing site: PDBJ
Revision 1.0Nov 27, 2019Provider: repository / Type: Initial release
Revision 1.1Nov 13, 2024Group: Data collection / Database references / Structure summary
Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / database_2 / pdbx_entry_details / pdbx_modification_feature
Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Mast/stem cell growth factor receptor Kit
hetero molecules


Theoretical massNumber of molelcules
Total (without water)38,2652
Polymers37,7501
Non-polymers5161
Water4,089227
1
A: Mast/stem cell growth factor receptor Kit
hetero molecules

A: Mast/stem cell growth factor receptor Kit
hetero molecules


Theoretical massNumber of molelcules
Total (without water)76,5304
Polymers75,4992
Non-polymers1,0312
Water362
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
crystal symmetry operation7_645y+1,x-1,-z1
Buried area2350 Å2
ΔGint-3 kcal/mol
Surface area27520 Å2
MethodPISA
Unit cell
Length a, b, c (Å)59.853, 59.853, 197.984
Angle α, β, γ (deg.)90.000, 90.000, 90.000
Int Tables number96
Space group name H-MP43212

-
Components

#1: Protein Mast/stem cell growth factor receptor Kit / SCFR / Piebald trait protein / PBT / Proto-oncogene c-Kit / Tyrosine-protein kinase Kit / p145 c- ...SCFR / Piebald trait protein / PBT / Proto-oncogene c-Kit / Tyrosine-protein kinase Kit / p145 c-kit / v-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog


Mass: 37749.535 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Details: kinase domain, residue 547-693 and 754-935 from UNP P10721, linked with TS
Source: (gene. exp.) Homo sapiens (human) / Gene: KIT, SCFR / Production host: unidentified baculovirus
References: UniProt: P10721, receptor protein-tyrosine kinase
#2: Chemical ChemComp-AWO / N-(5-ethyl-1,2-oxazol-3-yl)-N'-[4-(2-{[6-(4-ethylpyrazin-1(4H)-yl)pyrimidin-4-yl]amino}-1,3-thiazol-5-yl)phenyl]urea


Mass: 515.590 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C25H25N9O2S
#3: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 227 / Source method: isolated from a natural source / Formula: H2O
Has protein modificationY

-
Experimental details

-
Experiment

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

-
Sample preparation

CrystalDensity Matthews: 2.35 Å3/Da / Density % sol: 47.63 %
Crystal growTemperature: 291 K / Method: vapor diffusion, hanging drop
Details: 15% PEG 3350, 0.1M sodium citrate tribasic dihydrate, pH 5.6, 3% ethylene glycol, 3% 1,6-hexanediol

-
Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: NSRRC / Beamline: BL15A1 / Wavelength: 1 Å
DetectorType: RAYONIX MX300HE / Detector: CCD / Date: Apr 18, 2018
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1 Å / Relative weight: 1
ReflectionResolution: 1.88→30 Å / Num. obs: 30279 / % possible obs: 99.7 % / Redundancy: 5.1 % / Biso Wilson estimate: 30.42 Å2 / Rmerge(I) obs: 0.055 / Rpim(I) all: 0.027 / Rrim(I) all: 0.062 / Χ2: 1.051 / Net I/σ(I): 13.7 / Num. measured all: 154364
Reflection shell

Diffraction-ID: 1

Resolution (Å)Redundancy (%)Rmerge(I) obsNum. unique obsCC1/2Rpim(I) allRrim(I) allΧ2% possible all
1.88-1.955.20.65429350.8570.3180.7291.059100
1.95-2.035.20.44729770.9420.2170.4981.071100
2.03-2.125.20.31129670.9690.1510.3471.05100
2.12-2.235.20.22430070.980.1080.251.05100
2.23-2.375.20.16229670.9880.0780.1811.075100
2.37-2.555.10.12330020.9920.060.1371.05100
2.55-2.815.10.07830220.9960.0380.0871.011100
2.81-3.215.10.05430590.9970.0260.061.031100
3.21-4.054.90.0431130.9980.020.0451.057100
4.05-304.80.02532300.9990.0120.0271.0697

-
Processing

Software
NameVersionClassification
HKL-2000data scaling
PHENIXdev_2621refinement
PDB_EXTRACT3.24data extraction
RefinementResolution: 1.881→26.767 Å / SU ML: 0.19 / Cross valid method: THROUGHOUT / σ(F): 1.33 / Phase error: 24.06
RfactorNum. reflection% reflection
Rfree0.2306 1999 6.63 %
Rwork0.1798 --
obs0.1832 30161 99.59 %
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å
Displacement parametersBiso max: 126.92 Å2 / Biso mean: 42.0495 Å2 / Biso min: 20.67 Å2
Refinement stepCycle: final / Resolution: 1.881→26.767 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms2372 0 37 227 2636
Biso mean--31.4 48.17 -
Num. residues----298
Refine LS restraints
Refine-IDTypeDev idealNumber
X-RAY DIFFRACTIONf_bond_d0.0062482
X-RAY DIFFRACTIONf_angle_d0.8283362
X-RAY DIFFRACTIONf_chiral_restr0.052363
X-RAY DIFFRACTIONf_plane_restr0.005423
X-RAY DIFFRACTIONf_dihedral_angle_d11.352045
LS refinement shell

Refine-ID: X-RAY DIFFRACTION / Rfactor Rfree error: 0 / Total num. of bins used: 14

Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkNum. reflection all% reflection obs (%)
1.8808-1.92780.31541400.270919852125100
1.9278-1.97990.30081390.235819332072100
1.9799-2.03810.23961390.224119612100100
2.0381-2.10390.26961410.206519822123100
2.1039-2.17910.28771410.198519862127100
2.1791-2.26630.23241410.188219892130100
2.2663-2.36930.24171420.185419872129100
2.3693-2.49420.24271420.183920162158100
2.4942-2.65030.22121410.192519862127100
2.6503-2.85470.2451430.200720262169100
2.8547-3.14160.25041450.19520332178100
3.1416-3.59530.21231440.175920382182100
3.5953-4.52610.17271480.14520832231100
4.5261-26.76980.25661530.16742157231096
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)
13.4236-0.2025-0.355.626-0.44653.3779-0.0801-0.03450.3158-0.16730.07-0.0681-0.2091-0.0064-0.00390.1851-0.0153-0.06740.2439-0.00860.11538.711-7.3763-28.6497
22.37030.0181-1.44233.72431.51473.72520.00050.03630.0203-0.23720.0086-0.1135-0.06340.0721-0.01510.1898-0.0152-0.00130.15970.01940.179238.9635-10.4474-27.1716
33.0761-1.76130.94191.7344-0.17928.1551-0.2291-0.6613-0.63340.08870.0240.20980.9694-0.28410.20160.3508-0.03320.0080.229-0.00030.312231.8508-20.5273-11.3654
42.4209-0.4410.53633.4805-5.5689.5546-0.0534-0.358-0.06180.16720.1182-0.04990.0822-0.2022-0.10160.24980.0066-0.00070.2771-0.04690.219533.4637-10.7484-1.6693
52.3387-0.6615-1.01292.64960.39382.8680.01880.33310.0653-0.2796-0.01730.3534-0.1435-0.71350.00370.22170.0033-0.04830.35630.02360.244722.8254-7.9311-14.5154
66.1401-0.960.27793.26211.21222.97010.17690.0724-0.1646-0.2276-0.05010.67840.0684-1.0631-0.16920.2333-0.01210.01650.58410.02310.413411.1849-10.0351-5.0172
74.16590.45930.15965.6699-3.92895.96940.1355-0.09890.21230.29860.17060.3616-0.6017-0.5266-0.27790.25960.08150.04610.2887-0.03570.251320.32370.1387-0.2924
84.8088-3.72093.45265.6358-4.99224.47-0.2263-0.52310.00051.13170.0647-0.4246-0.35750.30190.17950.5136-0.0323-0.0320.3931-0.07470.282333.6921-4.38856.0944
Refinement TLS group
IDRefine-IDRefine TLS-IDSelection detailsAuth asym-IDAuth seq-ID
1X-RAY DIFFRACTION1chain 'A' and (resid 569 through 600 )A569 - 600
2X-RAY DIFFRACTION2chain 'A' and (resid 601 through 666 )A601 - 666
3X-RAY DIFFRACTION3chain 'A' and (resid 667 through 758 )A667 - 758
4X-RAY DIFFRACTION4chain 'A' and (resid 759 through 786 )A759 - 786
5X-RAY DIFFRACTION5chain 'A' and (resid 787 through 863 )A787 - 863
6X-RAY DIFFRACTION6chain 'A' and (resid 864 through 896 )A864 - 896
7X-RAY DIFFRACTION7chain 'A' and (resid 897 through 916 )A897 - 916
8X-RAY DIFFRACTION8chain 'A' and (resid 917 through 935 )A917 - 935

+
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