[English] 日本語
Yorodumi
- PDB-1t45: STRUCTURAL BASIS FOR THE AUTOINHIBITION AND STI-571 INHIBITION OF... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 1t45
TitleSTRUCTURAL BASIS FOR THE AUTOINHIBITION AND STI-571 INHIBITION OF C-KIT TYROSINE KINASE
ComponentsHomo sapiens v-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog
KeywordsTRANSFERASE ACTIVATOR / KINASE / AUTOINHIBITION
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 / detection of mechanical stimulus involved in sensory perception of sound / positive regulation of long-term neuronal synaptic plasticity / 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 / SH2 domain binding / B cell differentiation / 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 / Transferase(Phosphotransferase); domain 1 / 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
: / Mast/stem cell growth factor receptor Kit
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 1.9 Å
AuthorsMol, C.D. / Dougan, D.R. / Schneider, T.R. / Skene, R.J. / Kraus, M.L. / Scheibe, D.N. / Snell, G.P. / Zou, H. / Sang, B.C. / Wilson, K.P.
CitationJournal: J.Biol.Chem. / Year: 2004
Title: Structural basis for the autoinhibition and STI-571 inhibition of c-Kit tyrosine kinase.
Authors: Mol, C.D. / Dougan, D.R. / Schneider, T.R. / Skene, R.J. / Kraus, M.L. / Scheibe, D.N. / Snell, G.P. / Zou, H. / Sang, B.C. / Wilson, K.P.
History
DepositionApr 28, 2004Deposition site: RCSB / Processing site: RCSB
Revision 1.0Jun 15, 2004Provider: repository / Type: Initial release
Revision 1.1Apr 30, 2008Group: Version format compliance
Revision 1.2Jul 13, 2011Group: Advisory / Version format compliance
Revision 1.3Aug 23, 2017Group: Refinement description / Source and taxonomy / Category: entity_src_gen / software
Revision 1.4Aug 23, 2023Group: Data collection / Database references / Refinement description
Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / database_2 / pdbx_initial_refinement_model
Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession
Remark 999SEQUENCE THIS IS A RECEPTOR PROTEIN TYROSINE KINASE WITH A "SPLIT" KINASE DOMAIN. THUS THE TWO ...SEQUENCE THIS IS A RECEPTOR PROTEIN TYROSINE KINASE WITH A "SPLIT" KINASE DOMAIN. THUS THE TWO CONSERVED KINASE DOMAINS ARE INTERRUPTED BY A LARGE NON-CONSERVED INSERTION CALLED THE KINASE INSERTION DOMAIN (KID). IN THE CONSTRUCT THE KID RESIDUES 694-753 WERE DELETED AND REPLACED WITH TWO VECTOR RESIDUES (THR-SER).

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Homo sapiens v-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog


Theoretical massNumber of molelcules
Total (without water)37,6701
Polymers37,6701
Non-polymers00
Water2,990166
1


  • Idetical with deposited unit
  • defined by author
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Unit cell
Length a, b, c (Å)44.414, 77.230, 94.574
Angle α, β, γ (deg.)90.00, 90.00, 90.00
Int Tables number19
Space group name H-MP212121

-
Components

#1: Protein Homo sapiens v-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog / KIT


Mass: 37669.559 Da / Num. of mol.: 1 / Fragment: KIT Tyrosine Kinase
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: kit / Plasmid: PSXB1 / Production host: Spodoptera frugiperda (fall armyworm)
References: UniProt: P10721, GenBank: 4557695, EC: 2.7.1.112
#2: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 166 / 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: 2.2 Å3/Da / Density % sol: 42 %
Crystal growTemperature: 295 K / Method: vapor diffusion, sitting drop / pH: 7
Details: PEG, pH 7.00, VAPOR DIFFUSION, SITTING DROP, temperature 295K

-
Data collection

DiffractionMean temperature: 100 K
Diffraction sourceSource: SYNCHROTRON / Site: ALS / Beamline: 5.0.3 / Wavelength: 1 / Wavelength: 1 Å
DetectorType: ADSC QUANTUM 4 / Detector: CCD / Date: Jul 10, 2003 / Details: MIRRORS
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelength
IDWavelength (Å)Relative weight
111
211
ReflectionResolution: 1.9→30 Å / Num. all: 26260 / Num. obs: 26260 / % possible obs: 99.3 % / Observed criterion σ(F): 2 / Observed criterion σ(I): 4 / Redundancy: 4.1 % / Biso Wilson estimate: 20 Å2 / Rmerge(I) obs: 0.058 / Net I/σ(I): 12.6
Reflection shellResolution: 1.9→1.97 Å / Rmerge(I) obs: 0.345 / Mean I/σ(I) obs: 3.1 / % possible all: 96.5

-
Processing

Software
NameVersionClassification
HKL-2000data collection
SCALEPACKdata scaling
AMoREphasing
REFMAC5.1.19refinement
HKL-2000data reduction
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 1PKG

1pkg


Resolution: 1.9→20 Å / Cor.coef. Fo:Fc: 0.948 / Cor.coef. Fo:Fc free: 0.936 / SU B: 3.379 / SU ML: 0.1 / TLS residual ADP flag: LIKELY RESIDUAL / Cross valid method: THROUGHOUT / σ(F): 0 / ESU R: 0.17 / ESU R Free: 0.145 / Stereochemistry target values: MAXIMUM LIKELIHOOD / Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS
RfactorNum. reflection% reflectionSelection details
Rfree0.22154 1325 5.1 %RANDOM
Rwork0.19299 ---
all0.19446 24835 --
obs0.19446 24835 99.37 %-
Solvent computationIon probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.4 Å / Solvent model: BABINET MODEL WITH MASK
Displacement parametersBiso mean: 16.896 Å2
Baniso -1Baniso -2Baniso -3
1-0.05 Å20 Å20 Å2
2--1.7 Å20 Å2
3----1.75 Å2
Refinement stepCycle: LAST / Resolution: 1.9→20 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms2642 0 0 166 2808
Refine LS restraints
Refine-IDTypeDev idealDev ideal targetNumber
X-RAY DIFFRACTIONr_bond_refined_d0.0090.0222719
X-RAY DIFFRACTIONr_bond_other_d0.0020.022470
X-RAY DIFFRACTIONr_angle_refined_deg1.1121.9583679
X-RAY DIFFRACTIONr_angle_other_deg0.75935768
X-RAY DIFFRACTIONr_dihedral_angle_1_deg6.3035329
X-RAY DIFFRACTIONr_chiral_restr0.0650.2404
X-RAY DIFFRACTIONr_gen_planes_refined0.0040.022959
X-RAY DIFFRACTIONr_gen_planes_other0.0040.02548
X-RAY DIFFRACTIONr_nbd_refined0.2030.2587
X-RAY DIFFRACTIONr_nbd_other0.2280.23014
X-RAY DIFFRACTIONr_nbtor_other0.0830.21592
X-RAY DIFFRACTIONr_xyhbond_nbd_refined0.1420.2155
X-RAY DIFFRACTIONr_symmetry_vdw_refined0.1120.217
X-RAY DIFFRACTIONr_symmetry_vdw_other0.2450.277
X-RAY DIFFRACTIONr_symmetry_hbond_refined0.1170.214
X-RAY DIFFRACTIONr_mcbond_it0.5371.51653
X-RAY DIFFRACTIONr_mcangle_it0.8841.52675
X-RAY DIFFRACTIONr_scbond_it0.4961.51066
X-RAY DIFFRACTIONr_scangle_it0.7291.51002
LS refinement shellResolution: 1.9→1.949 Å / Total num. of bins used: 20 /
RfactorNum. reflection
Rfree0.28 85
Rwork0.228 1713
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)
11.1534-0.11890.00941.7019-0.11872.22160.0289-0.0128-0.0407-0.0333-0.04240.0159-0.1834-0.05130.01350.0187-0.0064-0.00210.02340.00450.07619.64414.5479.965
21.55820.1885-0.19072.3859-0.32842.0227-0.0148-0.0683-0.14490.08040.02140.1093-0.0543-0.0149-0.00670.0109-0.0037-0.00240.02050.00860.06994.6034.05330.616
Refinement TLS group
IDRefine-IDRefine TLS-IDAuth asym-IDLabel asym-IDAuth seq-IDLabel seq-ID
1X-RAY DIFFRACTION1AA547 - 6751 - 129
2X-RAY DIFFRACTION2AA676 - 935130 - 331

+
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