[English] 日本語
Yorodumi
- PDB-7khk: Crystal structure of KIT kinase domain with a small molecule inhi... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 7khk
TitleCrystal structure of KIT kinase domain with a small molecule inhibitor, PLX9486 (bezuclastinib) in the DFG-in state
ComponentsMast/stem cell growth factor receptor Kit
KeywordsTRANSFERASE/TRANSFERASE INHIBITOR / transferase / tyrosine-protein kinase / ATP-binding / kinase-kinase inhibitor complex / TRANSFERASE-TRANSFERASE INHIBITOR complex
Function / homologyChem-WEJ
Function and homology information
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.34 Å
AuthorsZhang, Y.
CitationJournal: Jama Oncol / Year: 2021
Title: Association of Combination of Conformation-Specific KIT Inhibitors With Clinical Benefit in Patients With Refractory Gastrointestinal Stromal Tumors: A Phase 1b/2a Nonrandomized Clinical Trial.
Authors: Wagner, A.J. / Severson, P.L. / Shields, A.F. / Patnaik, A. / Chugh, R. / Tinoco, G. / Wu, G. / Nespi, M. / Lin, J. / Zhang, Y. / Ewing, T. / Habets, G. / Burton, E.A. / Matusow, B. / Tsai, ...Authors: Wagner, A.J. / Severson, P.L. / Shields, A.F. / Patnaik, A. / Chugh, R. / Tinoco, G. / Wu, G. / Nespi, M. / Lin, J. / Zhang, Y. / Ewing, T. / Habets, G. / Burton, E.A. / Matusow, B. / Tsai, J. / Tsang, G. / Shellooe, R. / Carias, H. / Chan, K. / Rezaei, H. / Sanftner, L. / Marimuthu, A. / Spevak, W. / Ibrahim, P.N. / Inokuchi, K. / Alcantar, O. / Michelson, G. / Tsiatis, A.C. / Zhang, C. / Bollag, G. / Trent, J.C. / Tap, W.D.
History
DepositionOct 21, 2020Deposition site: RCSB / Processing site: RCSB
Revision 1.0Jul 7, 2021Provider: repository / Type: Initial release
Revision 1.1Aug 4, 2021Group: Database references / Category: citation
Item: _citation.journal_id_ISSN / _citation.pdbx_database_id_DOI ..._citation.journal_id_ISSN / _citation.pdbx_database_id_DOI / _citation.pdbx_database_id_PubMed / _citation.title
Revision 1.2Aug 11, 2021Group: Database references / Category: citation / database_2
Item: _citation.country / _citation.journal_abbrev ..._citation.country / _citation.journal_abbrev / _database_2.pdbx_DOI / _database_2.pdbx_database_accession
Revision 1.3Sep 29, 2021Group: Database references / Category: citation
Item: _citation.journal_volume / _citation.page_first / _citation.page_last
Revision 1.4Oct 18, 2023Group: Data collection / Refinement description
Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / pdbx_initial_refinement_model / struct_ncs_dom_lim
Item: _struct_ncs_dom_lim.beg_auth_comp_id / _struct_ncs_dom_lim.beg_label_asym_id ..._struct_ncs_dom_lim.beg_auth_comp_id / _struct_ncs_dom_lim.beg_label_asym_id / _struct_ncs_dom_lim.beg_label_comp_id / _struct_ncs_dom_lim.beg_label_seq_id / _struct_ncs_dom_lim.end_auth_comp_id / _struct_ncs_dom_lim.end_label_asym_id / _struct_ncs_dom_lim.end_label_comp_id / _struct_ncs_dom_lim.end_label_seq_id

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

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


Theoretical massNumber of molelcules
Total (without water)76,6314
Polymers75,9682
Non-polymers6632
Water55831
1
A: Mast/stem cell growth factor receptor Kit
hetero molecules


Theoretical massNumber of molelcules
Total (without water)38,3152
Polymers37,9841
Non-polymers3311
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
MethodPISA
2
B: Mast/stem cell growth factor receptor Kit
hetero molecules


Theoretical massNumber of molelcules
Total (without water)38,3152
Polymers37,9841
Non-polymers3311
Water0
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
MethodPISA
Unit cell
Length a, b, c (Å)57.984, 61.906, 206.769
Angle α, β, γ (deg.)90.000, 90.000, 90.000
Int Tables number19
Space group name H-MP212121
Noncrystallographic symmetry (NCS)NCS domain:
IDEns-IDDetails
11(chain A and (resid 567 through 596 or resid 601...
21(chain B and (resid 567 through 826 or resid 829 through 929))

NCS domain segments:

Ens-ID: 1

Dom-IDComponent-IDBeg auth comp-IDBeg label comp-IDEnd auth comp-IDEnd label comp-IDSelection detailsAuth asym-IDLabel asym-IDAuth seq-IDLabel seq-ID
11ASNASNGLYGLY(chain A and (resid 567 through 596 or resid 601...AA567 - 59626 - 55
12GLYGLYLYSLYS(chain A and (resid 567 through 596 or resid 601...AA601 - 62660 - 85
13SERSERLEULEU(chain A and (resid 567 through 596 or resid 601...AA631 - 68290 - 141
14ASPASPLYSLYS(chain A and (resid 567 through 596 or resid 601...AA765 - 818166 - 219
15SERSERARGARG(chain A and (resid 567 through 596 or resid 601...AA821 - 888222 - 289
16HISHISSERSER(chain A and (resid 567 through 596 or resid 601...AA894 - 929295 - 330
21ASNASNLYSLYS(chain B and (resid 567 through 826 or resid 829 through 929))BB567 - 82626 - 227
22ALAALASERSER(chain B and (resid 567 through 826 or resid 829 through 929))BB829 - 929230 - 330

-
Components

#1: Protein Mast/stem cell growth factor receptor Kit


Mass: 37984.066 Da / Num. of mol.: 2
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Production host: Escherichia coli (E. coli)
#2: Chemical ChemComp-WEJ / 4,5-dimethyl-N-(2-phenyl-1H-pyrrolo[2,3-b]pyridin-5-yl)-1H-pyrazole-3-carboxamide


Mass: 331.371 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C19H17N5O / Feature type: SUBJECT OF INVESTIGATION
#3: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 31 / 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: 2.44 Å3/Da / Density % sol: 49.64 %
Crystal growTemperature: 293 K / Method: vapor diffusion, sitting drop / Details: 0.1M Imidazole-HCl, pH7.0, 1M sodium acetate

-
Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: ALS / Beamline: 8.3.1 / Wavelength: 1.116 Å
DetectorType: ADSC QUANTUM 210 / Detector: CCD / Date: Jun 10, 2012
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1.116 Å / Relative weight: 1
ReflectionResolution: 2.34→96.06 Å / Num. obs: 31070 / % possible obs: 96.06 % / Redundancy: 4.2 % / Rsym value: 0.058 / Net I/σ(I): 10.9
Reflection shellResolution: 2.34→2.47 Å / Num. unique obs: 3351 / Rsym value: 0.606

-
Processing

Software
NameVersionClassification
PHENIX1.11.1_2575refinement
PDB_EXTRACT3.25data extraction
MOSFLMdata reduction
SCALAdata scaling
MOLREPphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 1t45

1t45


Resolution: 2.34→46.056 Å / SU ML: 0.36 / Cross valid method: THROUGHOUT / σ(F): 1.34 / Phase error: 30.35 / Stereochemistry target values: ML
RfactorNum. reflection% reflection
Rfree0.2854 1534 4.94 %
Rwork0.2452 29536 -
obs0.2472 31070 96.06 %
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT BULK SOLVENT MODEL
Displacement parametersBiso max: 172.83 Å2 / Biso mean: 81.1681 Å2 / Biso min: 29.44 Å2
Refinement stepCycle: final / Resolution: 2.34→46.056 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms4440 0 50 31 4521
Biso mean--107.14 56.09 -
Num. residues----557
Refine LS restraints
Refine-IDTypeDev idealNumber
X-RAY DIFFRACTIONf_bond_d0.0084585
X-RAY DIFFRACTIONf_angle_d0.9926198
X-RAY DIFFRACTIONf_chiral_restr0.055672
X-RAY DIFFRACTIONf_plane_restr0.007778
X-RAY DIFFRACTIONf_dihedral_angle_d17.8542714
Refine LS restraints NCS
Ens-IDDom-IDAuth asym-IDNumberRefine-IDRmsType
11A2398X-RAY DIFFRACTION14.433TORSIONAL
12B2398X-RAY DIFFRACTION14.433TORSIONAL
LS refinement shell

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

Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection Rwork% reflection obs (%)
2.3401-2.41560.39711450.3352234986
2.4156-2.50190.35751000.3058250290
2.5019-2.60210.33551410.2767252593
2.6021-2.72050.31641550.2854261695
2.7205-2.86390.29611380.2697270598
2.8639-3.04330.34331220.2807278499
3.0433-3.27820.30071570.2631273099
3.2782-3.6080.27591210.25762804100
3.608-4.12980.26891600.23992796100
4.1298-5.2020.27111510.21452815100
5.202-46.0560.26331440.228291097

+
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