[English] 日本語
Yorodumi
- PDB-6kla: Crystal structure of human c-KIT kinase domain in complex with co... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 6kla
TitleCrystal structure of human c-KIT kinase domain in complex with compound 15a
ComponentsMast/stem cell growth factor receptor Kit
KeywordsTRANSFERASE / tyrosine kinase inhibitor / kinase phosphorylation / ATP competitor / transmembrane receptor protein
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 / melanocyte adhesion / positive regulation of pyloric antrum smooth muscle contraction / positive regulation of colon smooth muscle contraction / melanocyte migration / stem cell factor receptor activity / mast cell proliferation / positive regulation of vascular associated smooth muscle cell differentiation / Kit signaling pathway / positive regulation of dendritic cell cytokine production / tongue development / positive regulation of small intestine smooth muscle contraction / positive regulation of mast cell cytokine production / mast cell differentiation / mast cell chemotaxis / Fc receptor signaling pathway / immature B cell differentiation / epithelial cell proliferation / melanocyte differentiation / positive regulation of long-term neuronal synaptic plasticity / primordial germ cell migration / positive regulation of pseudopodium assembly / detection of mechanical stimulus involved in sensory perception of sound / megakaryocyte development / erythropoietin-mediated signaling pathway / somatic stem cell population maintenance / pigmentation / embryonic hemopoiesis / digestive tract development / lamellipodium assembly / Regulation of KIT signaling / stem cell population maintenance / positive regulation of Notch signaling pathway / growth factor binding / positive regulation of tyrosine phosphorylation of STAT protein / Developmental Lineage of Mammary Gland Alveolar Cells / ovarian follicle development / hemopoiesis / cytokine binding / hematopoietic progenitor cell differentiation / T cell differentiation / response to cadmium ion / Developmental Lineage of Mammary Gland Luminal Epithelial Cells / B cell differentiation / stem cell differentiation / TFAP2 (AP-2) family regulates transcription of growth factors and their receptors / transmembrane receptor protein tyrosine kinase activity / male gonad development / Transcriptional and post-translational regulation of MITF-M expression and activity / visual learning / acrosomal vesicle / SH2 domain binding / erythrocyte differentiation / positive regulation of receptor signaling pathway via JAK-STAT / Signaling by phosphorylated juxtamembrane, extracellular and kinase domain KIT mutants / mast cell degranulation / cell chemotaxis / Signaling by SCF-KIT / receptor protein-tyrosine kinase / cytokine-mediated signaling pathway / Constitutive Signaling by Aberrant PI3K in Cancer / cytoplasmic side of plasma membrane / regulation of cell shape / cell-cell junction / actin cytoskeleton organization / PIP3 activates AKT signaling / regulation of cell population proliferation / protein autophosphorylation / cell migration / PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling / RAF/MAP kinase cascade / protease binding / protein tyrosine kinase activity / spermatogenesis / positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction / positive regulation of MAPK cascade / signaling receptor complex / positive regulation of cell migration / inflammatory response / external side of plasma membrane / positive regulation of cell population proliferation / signal transduction / protein homodimerization activity / : / ATP binding / metal ion binding / plasma membrane
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. / Immunoglobulin subtype / Immunoglobulin / Tyrosine-protein kinase, active site / Protein tyrosine and serine/threonine kinase / Serine-threonine/tyrosine-protein kinase, catalytic domain / Phosphorylase Kinase; domain 1 / Phosphorylase Kinase; domain 1 / Transferase(Phosphotransferase) domain 1 / Transferase(Phosphotransferase); 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-DJX / Mast/stem cell growth factor receptor Kit
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / molecular replacement / Resolution: 2.109 Å
AuthorsWu, T.S. / Peng, Y.H. / Hsueh, C.C. / Wu, S.Y.
CitationJournal: J.Med.Chem. / Year: 2019
Title: Identification of a Multitargeted Tyrosine Kinase Inhibitor for the Treatment of Gastrointestinal Stromal Tumors and Acute Myeloid Leukemia.
Authors: Lin, W.H. / Wu, S.Y. / Yeh, T.K. / Chen, C.T. / Song, J.S. / Shiao, H.Y. / Kuo, C.C. / Hsu, T. / Lu, C.T. / Wang, P.C. / Wu, T.S. / Peng, Y.H. / Lin, H.Y. / Chen, C.P. / Weng, Y.L. / Kung, F. ...Authors: Lin, W.H. / Wu, S.Y. / Yeh, T.K. / Chen, C.T. / Song, J.S. / Shiao, H.Y. / Kuo, C.C. / Hsu, T. / Lu, C.T. / Wang, P.C. / Wu, T.S. / Peng, Y.H. / Lin, H.Y. / Chen, C.P. / Weng, Y.L. / Kung, F.C. / Wu, M.H. / Su, Y.C. / Huang, K.W. / Chou, L.H. / Hsueh, C.C. / Yen, K.J. / Kuo, P.C. / Huang, C.L. / Chen, L.T. / Shih, C. / Tsai, H.J. / Jiaang, W.T.
History
DepositionJul 30, 2019Deposition site: PDBJ / Processing site: PDBJ
Revision 1.0Nov 27, 2019Provider: repository / Type: Initial release
Revision 1.1Jan 8, 2020Group: Database references / Category: citation / citation_author
Item: _citation.journal_volume / _citation.page_first ..._citation.journal_volume / _citation.page_first / _citation.page_last / _citation.title / _citation_author.name
Revision 1.2Nov 22, 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

-
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)38,0512
Polymers37,6701
Non-polymers3811
Water84747
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)76,1024
Polymers75,3392
Non-polymers7632
Water362
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
crystal symmetry operation7_555y,x,-z1
Buried area1850 Å2
ΔGint-4 kcal/mol
Surface area28200 Å2
MethodPISA
Unit cell
Length a, b, c (Å)63.205, 63.205, 196.142
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: 37669.559 Da / Num. of mol.: 1
Fragment: kinase domain, residue 547-693 and 754-935 from UNP P10721, linked with TS
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: KIT, SCFR / Plasmid: pBacPAK8 / Cell line (production host): Sf9 / Production host: Spodoptera frugiperda (fall armyworm)
References: UniProt: P10721, receptor protein-tyrosine kinase
#2: Chemical ChemComp-DJX / N-[6-(4-ethylpiperazin-1-yl)-2-methyl-pyrimidin-4-yl]-5-pyridin-4-yl-1,3-thiazol-2-amine / 6-(4-ethylpiperazin-1-yl)-2-methyl-N-(5-(pyridin-4-yl)thiazol-2-yl)pyrimidin-4-amine


Mass: 381.498 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C19H23N7S / Feature type: SUBJECT OF INVESTIGATION
#3: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 47 / Source method: isolated from a natural source / Formula: H2O
Has ligand of interestY

-
Experimental details

-
Experiment

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

-
Sample preparation

CrystalDensity Matthews: 2.6 Å3/Da / Density % sol: 52.69 %
Crystal growTemperature: 291.15 K / Method: vapor diffusion, hanging drop / pH: 5.6
Details: PEG 4000, sodium citrate tribasic dihydrate, pH5.6, glycerol

-
Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: NSRRC / Beamline: TPS 05A / Wavelength: 1 Å
DetectorType: RAYONIX MX300-HS / Detector: CCD / Date: Mar 4, 2017 / Details: LN2-Cooled Fixed-Exit Double
RadiationMonochromator: Si(111) / Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1 Å / Relative weight: 1
ReflectionResolution: 2.109→30 Å / Num. obs: 23502 / % possible obs: 98.3 % / Redundancy: 7.2 % / Biso Wilson estimate: 45.25 Å2 / Rmerge(I) obs: 0.066 / Rpim(I) all: 0.026 / Rrim(I) all: 0.071 / Χ2: 1.051 / Net I/σ(I): 12.5
Reflection shell

Diffraction-ID: 1

Resolution (Å)Redundancy (%)Rmerge(I) obsNum. unique obsCC1/2Rpim(I) allRrim(I) allΧ2% possible all
2.11-2.194.90.62121230.8990.2780.6841.05992
2.19-2.276.10.50922850.9590.2140.5541.02798.1
2.27-2.387.20.40922940.9830.1610.441.07399
2.38-2.57.80.3423470.9860.1290.3641.03199.3
2.5-2.6680.2323430.9930.0860.2461.08999.3
2.66-2.8680.14823510.9960.0550.1581.04699.4
2.86-3.157.90.09423630.9960.0350.11.05899.5
3.15-3.617.60.06223830.9980.0240.0661.05899.5
3.61-4.547.30.04724440.9980.0180.051.02599.1
4.54-306.80.04325690.9980.0170.0471.03897.7

-
Phasing

PhasingMethod: molecular replacement

-
Processing

Software
NameVersionClassificationNB
DENZOdata reduction
SCALEPACKdata scaling
PHASERphasing
PHENIXdev_2621refinement
PDB_EXTRACT3.25data extraction
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 1T46

1t46


Resolution: 2.109→29.482 Å / SU ML: 0.24 / Cross valid method: THROUGHOUT / σ(F): 1.34 / Phase error: 26.78
RfactorNum. reflection% reflection
Rfree0.2239 1996 8.52 %
Rwork0.183 --
obs0.1866 23419 98.28 %
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å
Displacement parametersBiso max: 148.74 Å2 / Biso mean: 64.5664 Å2 / Biso min: 29.29 Å2
Refinement stepCycle: final / Resolution: 2.109→29.482 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms2423 0 27 47 2497
Biso mean--49.86 56.03 -
Num. residues----309
Refine LS restraints
Refine-IDTypeDev idealNumber
X-RAY DIFFRACTIONf_bond_d0.0072560
X-RAY DIFFRACTIONf_angle_d0.833465
X-RAY DIFFRACTIONf_chiral_restr0.052374
X-RAY DIFFRACTIONf_plane_restr0.005438
X-RAY DIFFRACTIONf_dihedral_angle_d10.222119
LS refinement shell

Refine-ID: X-RAY DIFFRACTION / Rfactor Rfree error: 0

Resolution (Å)Rfactor RfreeNum. reflection Rfree% reflection Rfree (%)Rfactor RworkNum. reflection Rwork% reflection obs (%)
2.1094-2.16220.36881251133990
2.1622-2.22060.2657138147497
2.2206-2.28590.2927140149398
2.2859-2.35970.2977139150298
2.3597-2.4440.2697140150899
2.444-2.54180.2642143153399
2.5418-2.65740.28142152199
2.6574-2.79740.2856142152499
2.7974-2.97250.2717142153499
2.9725-3.20180.26231461566100
3.2018-3.52350.2131451564100
3.5235-4.03230.21761470.17241571100
4.0323-5.0760.18961480.1394159599
5.076-29.4820.18291590.1639169998
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)
16.7458-2.1375-1.41173.0633.99115.85140.36451.0469-0.4644-0.01150.2297-0.52570.95170.3462-0.70870.73570.07-0.10720.8679-0.11440.67537.10660.843122.2893
27.73251.52360.43768.87770.54266.185-0.086-0.70240.06250.1594-0.07340.27110.0188-0.33970.17410.29090.00930.02620.39870.01310.192315.908211.821529.4448
39.0952-4.41183.41887.8753-3.04253.7584-0.0282-0.38570.07450.71120.42030.7173-0.2433-0.3534-0.4110.3419-0.06080.05550.3969-0.04480.279713.893611.657627.1093
44.14574.1674-5.56819.5754-6.20127.641-0.2498-0.2037-0.14630.31980.2388-0.64240.66120.3679-0.15160.42970.0181-0.10060.4601-0.08920.593227.90574.448528.5177
52.06860.3080.3962.81472.15276.57120.02330.1131-0.0521-0.06950.07560.2140.4559-0.5966-0.09430.3754-0.0856-0.01950.38710.03010.379614.84645.647415.7819
63.12071.22833.92565.78051.31965.975-0.32270.37320.1004-0.54520.27350.08380.09130.049-0.05620.3814-0.07180.06710.4137-0.01590.256718.76333.5240.9536
72.4162-1.20180.52823.16390.59533.6242-0.0138-0.2656-0.52350.40860.2464-0.00241.1050.1444-0.21220.7074-0.0008-0.0040.42850.02260.449822.2022-10.287511.1728
86.7392-1.29891.75795.45160.0835.53070.11050.45130.1896-0.51710.1146-0.55260.23850.4289-0.160.4815-0.0070.15130.5205-0.10970.408828.9063-3.7273-2.6573
Refinement TLS group
IDRefine-IDRefine TLS-IDSelection detailsAuth asym-IDAuth seq-ID
1X-RAY DIFFRACTION1chain 'A' and (resid 554 through 579 )A554 - 579
2X-RAY DIFFRACTION2chain 'A' and (resid 580 through 600 )A580 - 600
3X-RAY DIFFRACTION3chain 'A' and (resid 601 through 630 )A601 - 630
4X-RAY DIFFRACTION4chain 'A' and (resid 631 through 647 )A631 - 647
5X-RAY DIFFRACTION5chain 'A' and (resid 648 through 758 )A648 - 758
6X-RAY DIFFRACTION6chain 'A' and (resid 759 through 786 )A759 - 786
7X-RAY DIFFRACTION7chain 'A' and (resid 787 through 896 )A787 - 896
8X-RAY DIFFRACTION8chain 'A' and (resid 897 through 931 )A897 - 931

+
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