+Open data
-Basic information
Entry | Database: PDB / ID: 3g0e | ||||||
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Title | KIT kinase domain in complex with sunitinib | ||||||
Components | Mast/stem cell growth factor receptor | ||||||
Keywords | TRANSFERASE / KIT Kinase domain / Sutent binding / drug resistance / ATP-binding / Disease mutation / Glycoprotein / Immunoglobulin domain / Kinase / Membrane / Nucleotide-binding / Phosphoprotein / Polymorphism / Proto-oncogene / Receptor / Transmembrane / Tyrosine-protein kinase | ||||||
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 / stem cell factor receptor activity / hematopoietic stem cell migration / melanocyte adhesion / positive regulation of pyloric antrum smooth muscle contraction / positive regulation of colon smooth muscle contraction / erythropoietin-mediated signaling pathway / positive regulation of vascular associated smooth muscle cell differentiation / melanocyte migration / positive regulation of dendritic cell cytokine production / Kit signaling pathway / regulation of bile acid metabolic process / positive regulation of small intestine smooth muscle contraction / mast cell differentiation / positive regulation of mast cell proliferation / 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 / positive regulation of mast cell cytokine production / immature B cell differentiation / melanocyte differentiation / germ cell migration / lymphoid progenitor cell differentiation / myeloid progenitor cell differentiation / digestive tract development / negative regulation of programmed cell death / embryonic hemopoiesis / lamellipodium assembly / pigmentation / tongue development / megakaryocyte development / Regulation of KIT signaling / mast cell degranulation / stem cell population maintenance / positive regulation of Notch signaling pathway / cytokine binding / negative regulation of reproductive process / negative regulation of developmental process / spermatid development / growth factor binding / somatic stem cell population maintenance / hemopoiesis / T cell differentiation / ectopic germ cell programmed cell death / hematopoietic progenitor cell differentiation / positive regulation of phospholipase C activity / response to cadmium ion / ovarian follicle development / positive regulation of tyrosine phosphorylation of STAT protein / TFAP2 (AP-2) family regulates transcription of growth factors and their receptors / transmembrane receptor protein tyrosine kinase activity / SH2 domain binding / cell chemotaxis / B cell differentiation / erythrocyte differentiation / acrosomal vesicle / Signaling by phosphorylated juxtamembrane, extracellular and kinase domain KIT mutants / epithelial cell proliferation / stem cell differentiation / positive regulation of receptor signaling pathway via JAK-STAT / visual learning / Signaling by SCF-KIT / cytoplasmic side of plasma membrane / receptor protein-tyrosine kinase / fibrillar center / cytokine-mediated signaling pathway / male gonad development / Constitutive Signaling by Aberrant PI3K in Cancer / positive regulation of DNA-binding transcription factor activity / cell-cell junction / PIP3 activates AKT signaling / regulation of cell population proliferation / regulation of cell shape / PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling / actin cytoskeleton organization / RAF/MAP kinase cascade / spermatogenesis / protein tyrosine kinase activity / protease binding / positive regulation of MAPK cascade / protein autophosphorylation / positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction / receptor complex / intracellular signal transduction / positive regulation of cell migration / inflammatory response Similarity search - Function | ||||||
Biological species | Homo sapiens (human) | ||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 1.6 Å | ||||||
Authors | Gajiwala, K.S. / Wu, J.C. / Lunney, E.A. / Gemetri, G.D. | ||||||
Citation | Journal: Proc.Natl.Acad.Sci.USA / Year: 2009 Title: KIT kinase mutants show unique mechanisms of drug resistance to imatinib and sunitinib in gastrointestinal stromal tumor patients. Authors: Gajiwala, K.S. / Wu, J.C. / Christensen, J. / Deshmukh, G.D. / Diehl, W. / DiNitto, J.P. / English, J.M. / Greig, M.J. / He, Y.A. / Jacques, S.L. / Lunney, E.A. / McTigue, M. / Molina, D. / ...Authors: Gajiwala, K.S. / Wu, J.C. / Christensen, J. / Deshmukh, G.D. / Diehl, W. / DiNitto, J.P. / English, J.M. / Greig, M.J. / He, Y.A. / Jacques, S.L. / Lunney, E.A. / McTigue, M. / Molina, D. / Quenzer, T. / Wells, P.A. / Yu, X. / Zhang, Y. / Zou, A. / Emmett, M.R. / Marshall, A.G. / Zhang, H.M. / Demetri, G.D. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 3g0e.cif.gz | 89 KB | Display | PDBx/mmCIF format |
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PDB format | pdb3g0e.ent.gz | 65.7 KB | Display | PDB format |
PDBx/mmJSON format | 3g0e.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/g0/3g0e ftp://data.pdbj.org/pub/pdb/validation_reports/g0/3g0e | HTTPS FTP |
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-Related structure data
Related structure data | 3g0fC 1t45S C: citing same article (ref.) S: Starting model for refinement |
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Similar structure data |
-Links
-Assembly
Deposited unit |
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1 |
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Unit cell |
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-Components
#1: Protein | Mass: 38217.180 Da / Num. of mol.: 1 / Fragment: Kinase domain - KID deleted / Mutation: 694-753 deleted, replaced with TS Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: KIT / Production host: Spodoptera frugiperda (fall armyworm) References: UniProt: P10721, receptor protein-tyrosine kinase |
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#2: Chemical | ChemComp-B49 / |
#3: Water | ChemComp-HOH / |
Sequence details | RESIDUES 694-753 DELETED, REPLACED WITH TS |
-Experimental details
-Experiment
Experiment | Method: X-RAY DIFFRACTION / Number of used crystals: 1 |
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-Sample preparation
Crystal | Density Matthews: 2.37 Å3/Da / Density % sol: 48.19 % |
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Crystal grow | Temperature: 286 K / Method: vapor diffusion, hanging drop / pH: 9 Details: Reservoir: 10% PEG6000, 0.1 M bicine, pH 9; Protein: 6.6 mg/ml in 0.25M NaCl, 25mM Tris, pH 7.5, 1mM EDTA, 0.5mM TCEP, VAPOR DIFFUSION, HANGING DROP, temperature 286K |
-Data collection
Diffraction | Mean temperature: 98 K |
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Diffraction source | Source: SYNCHROTRON / Site: ALS / Beamline: 5.0.1 / Wavelength: 1 Å |
Detector | Type: ADSC QUANTUM 210 / Detector: CCD / Date: Mar 10, 2007 / Details: Mirrors |
Radiation | Monochromator: Mirrors / Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 1 Å / Relative weight: 1 |
Reflection | Resolution: 1.6→20 Å / Num. all: 48722 / Num. obs: 48589 / % possible obs: 99.7 % / Redundancy: 4.9 % / Biso Wilson estimate: 19.7 Å2 / Rmerge(I) obs: 0.039 / Rsym value: 0.039 |
Reflection shell | Resolution: 1.6→1.66 Å / Redundancy: 5 % / Rmerge(I) obs: 0.241 / Mean I/σ(I) obs: 6.6 / Num. unique all: 4803 / Rsym value: 0.241 / % possible all: 100 |
-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: 1T45 Resolution: 1.6→20 Å / Isotropic thermal model: Isotropic / Cross valid method: THROUGHOUT / σ(F): 0 / σ(I): 0 / Stereochemistry target values: Engh & Huber
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Displacement parameters | Biso mean: 18.7 Å2 | |||||||||||||||||||||||||
Refine analyze |
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Refinement step | Cycle: LAST / Resolution: 1.6→20 Å
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Refine LS restraints |
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LS refinement shell | Resolution: 1.6→1.7 Å / Rfactor Rfree error: 0.012
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