[English] 日本語
Yorodumi
- PDB-6hd6: ABL1 IN COMPLEX WITH COMPOUND6 AND IMATINIB (STI-571) -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 6hd6
TitleABL1 IN COMPLEX WITH COMPOUND6 AND IMATINIB (STI-571)
ComponentsTyrosine-protein kinase ABL1
KeywordsTRANSFERASE / PHOSPHOTRANSFERASE / Inhibitor complex
Function / homology
Function and homology information


transitional one stage B cell differentiation / Role of ABL in ROBO-SLIT signaling / cerebellum morphogenesis / regulation of extracellular matrix organization / HDR through Single Strand Annealing (SSA) / B cell proliferation involved in immune response / B-1 B cell homeostasis / RHO GTPases Activate WASPs and WAVEs / neuroepithelial cell differentiation / positive regulation of Wnt signaling pathway, planar cell polarity pathway ...transitional one stage B cell differentiation / Role of ABL in ROBO-SLIT signaling / cerebellum morphogenesis / regulation of extracellular matrix organization / HDR through Single Strand Annealing (SSA) / B cell proliferation involved in immune response / B-1 B cell homeostasis / RHO GTPases Activate WASPs and WAVEs / neuroepithelial cell differentiation / positive regulation of Wnt signaling pathway, planar cell polarity pathway / alpha-beta T cell differentiation / microspike assembly / MLL4 and MLL3 complexes regulate expression of PPARG target genes in adipogenesis and hepatic steatosis / Turbulent (oscillatory, disturbed) flow shear stress activates signaling by PIEZO1 and integrins in endothelial cells / activated T cell proliferation / protein localization to cytoplasmic microtubule plus-end / Cyclin D associated events in G1 / DNA conformation change / response to epinephrine / phospholipase C-inhibiting G protein-coupled receptor signaling pathway / negative regulation of ubiquitin-protein transferase activity / podocyte apoptotic process / Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks / Bergmann glial cell differentiation / regulation of postsynaptic specialization assembly / regulation of cellular senescence / positive regulation of phospholipase C/protein kinase C signal transduction / regulation of modification of synaptic structure / delta-catenin binding / RUNX1 regulates transcription of genes involved in differentiation of HSCs / circulatory system development / positive regulation of extracellular matrix organization / Regulation of actin dynamics for phagocytic cup formation / neuropilin signaling pathway / neuropilin binding / Myogenesis / negative regulation of mitotic cell cycle / bubble DNA binding / spleen development / positive regulation of establishment of T cell polarity / neuromuscular process controlling balance / regulation of T cell differentiation / positive regulation of blood vessel branching / proline-rich region binding / post-embryonic development / platelet-derived growth factor receptor signaling pathway / syntaxin binding / positive regulation of dendrite development / B cell proliferation / regulation of Cdc42 protein signal transduction / negative regulation of cell-cell adhesion / negative regulation of cellular senescence / regulation of axon extension / mitogen-activated protein kinase binding / positive regulation of cell migration involved in sprouting angiogenesis / positive regulation of osteoblast proliferation / neural tube closure / thymus development / platelet-derived growth factor receptor-beta signaling pathway / cell leading edge / negative regulation of endothelial cell apoptotic process / myoblast proliferation / negative regulation of BMP signaling pathway / associative learning / negative regulation of long-term synaptic potentiation / cardiac muscle cell proliferation / regulation of microtubule polymerization / phagocytosis / ephrin receptor signaling pathway / cellular response to transforming growth factor beta stimulus / positive regulation of focal adhesion assembly / positive regulation of vasoconstriction / positive regulation of substrate adhesion-dependent cell spreading / endothelial cell migration / positive regulation of stress fiber assembly / substrate adhesion-dependent cell spreading / negative regulation of double-strand break repair via homologous recombination / positive regulation of T cell migration / ephrin receptor binding / positive regulation of mitotic cell cycle / four-way junction DNA binding / ruffle / positive regulation of interleukin-2 production / signal transduction in response to DNA damage / phosphotyrosine residue binding / actin filament polymerization / peptidyl-tyrosine phosphorylation / positive regulation of endothelial cell migration / SH2 domain binding / B cell receptor signaling pathway / integrin-mediated signaling pathway / response to endoplasmic reticulum stress / positive regulation of fibroblast proliferation / protein serine/threonine kinase activator activity / positive regulation of release of sequestered calcium ion into cytosol / regulation of actin cytoskeleton organization / protein kinase C binding / non-specific protein-tyrosine kinase / non-membrane spanning protein tyrosine kinase activity / positive regulation of type II interferon production
Similarity search - Function
F-actin binding / F-actin binding / F-actin binding domain (FABD) / Tyrosine-protein kinase ABL, SH2 domain / : / SH3 domain / SH2 domain / Src homology 2 (SH2) domain profile. / Src homology 2 domains / SH2 domain ...F-actin binding / F-actin binding / F-actin binding domain (FABD) / Tyrosine-protein kinase ABL, SH2 domain / : / SH3 domain / SH2 domain / Src homology 2 (SH2) domain profile. / Src homology 2 domains / SH2 domain / Src homology 3 domains / SH2 domain superfamily / SH3-like domain superfamily / Src homology 3 (SH3) domain profile. / SH3 domain / Tyrosine-protein kinase, catalytic domain / Tyrosine kinase, catalytic domain / Tyrosine protein kinases specific active-site signature. / 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 / Protein kinase, ATP binding site / Protein kinases ATP-binding region signature. / 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-FYH / Chem-STI / Tyrosine-protein kinase ABL1
Similarity search - Component
Biological speciesMus musculus (house mouse)
MethodX-RAY DIFFRACTION / SYNCHROTRON / FOURIER SYNTHESIS / Resolution: 2.3 Å
AuthorsCowan-Jacob, S.W.
CitationJournal: J. Med. Chem. / Year: 2018
Title: Discovery of Asciminib (ABL001), an Allosteric Inhibitor of the Tyrosine Kinase Activity of BCR-ABL1.
Authors: Schoepfer, J. / Jahnke, W. / Berellini, G. / Buonamici, S. / Cotesta, S. / Cowan-Jacob, S.W. / Dodd, S. / Drueckes, P. / Fabbro, D. / Gabriel, T. / Groell, J.M. / Grotzfeld, R.M. / Hassan, A. ...Authors: Schoepfer, J. / Jahnke, W. / Berellini, G. / Buonamici, S. / Cotesta, S. / Cowan-Jacob, S.W. / Dodd, S. / Drueckes, P. / Fabbro, D. / Gabriel, T. / Groell, J.M. / Grotzfeld, R.M. / Hassan, A.Q. / Henry, C. / Iyer, V. / Jones, D. / Lombardo, F. / Loo, A. / Manley, P.W. / Pelle, X. / Rummel, G. / Salem, B. / Warmuth, M. / Wylie, A.A. / Zoller, T. / Marzinzik, A.L. / Furet, P.
History
DepositionAug 17, 2018Deposition site: PDBE / Processing site: PDBE
Revision 1.0Sep 12, 2018Provider: repository / Type: Initial release
Revision 1.1Oct 10, 2018Group: Data collection / 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.identifier_ORCID / _citation_author.name
Revision 1.2May 15, 2024Group: Data collection / Database references / Structure summary
Category: chem_comp / chem_comp_atom ...chem_comp / chem_comp_atom / chem_comp_bond / database_2
Item: _chem_comp.pdbx_synonyms / _database_2.pdbx_DOI / _database_2.pdbx_database_accession

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Tyrosine-protein kinase ABL1
B: Tyrosine-protein kinase ABL1
hetero molecules


Theoretical massNumber of molelcules
Total (without water)68,8906
Polymers67,4872
Non-polymers1,4034
Water6,936385
1
A: Tyrosine-protein kinase ABL1
hetero molecules


Theoretical massNumber of molelcules
Total (without water)34,6534
Polymers33,7441
Non-polymers9093
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
MethodPISA
2
B: Tyrosine-protein kinase ABL1
hetero molecules


Theoretical massNumber of molelcules
Total (without water)34,2372
Polymers33,7441
Non-polymers4941
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
MethodPISA
Unit cell
Length a, b, c (Å)42.080, 65.201, 66.347
Angle α, β, γ (deg.)73.30, 79.82, 84.54
Int Tables number1
Space group name H-MP1

-
Components

#1: Protein Tyrosine-protein kinase ABL1 / Abelson murine leukemia viral oncogene homolog 1 / Abelson tyrosine-protein kinase 1 / Proto- ...Abelson murine leukemia viral oncogene homolog 1 / Abelson tyrosine-protein kinase 1 / Proto-oncogene c-Abl / p150


Mass: 33743.523 Da / Num. of mol.: 2 / Fragment: KINASE DOMAIN
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Mus musculus (house mouse) / Gene: Abl1, Abl / Production host: Spodoptera frugiperda (fall armyworm) / Variant (production host): SF9
References: UniProt: P00520, non-specific protein-tyrosine kinase
#2: Chemical ChemComp-CL / CHLORIDE ION


Mass: 35.453 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: Cl
#3: Chemical ChemComp-FYH / 3-(morpholin-4-ylmethyl)-~{N}-[4-(trifluoromethyloxy)phenyl]benzamide


Mass: 380.361 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C19H19F3N2O3
#4: Chemical ChemComp-STI / 4-(4-METHYL-PIPERAZIN-1-YLMETHYL)-N-[4-METHYL-3-(4-PYRIDIN-3-YL-PYRIMIDIN-2-YLAMINO)-PHENYL]-BENZAMIDE / STI-571 / IMATINIB


Mass: 493.603 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C29H31N7O / Comment: medication, inhibitor*YM
#5: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 385 / 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: 2.54 Å3/Da / Density % sol: 51.58 %
Crystal growTemperature: 277 K / Method: vapor diffusion, hanging drop / Details: 21.4 % PEG 4000, 0.2 M MGCL2, 0.1 M MES PH 5.6

-
Data collection

DiffractionMean temperature: 100 K
Diffraction sourceSource: SYNCHROTRON / Site: SLS / Beamline: X10SA / Wavelength: 0.9781 Å
DetectorType: MARRESEARCH / Detector: CCD / Date: Feb 22, 2008
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.9781 Å / Relative weight: 1
ReflectionResolution: 2.3→37.34 Å / Num. obs: 27927 / % possible obs: 94.4 % / Redundancy: 1.99 % / Rmerge(I) obs: 0.048 / Net I/σ(I): 14.29
Reflection shellResolution: 2.3→2.38 Å / Redundancy: 1.99 % / Rmerge(I) obs: 0.244 / Mean I/σ(I) obs: 3.16 / % possible all: 95.2

-
Processing

Software
NameVersionClassification
REFMAC5.3.0040refinement
XDSdata reduction
XSCALEdata scaling
REFMACphasing
RefinementMethod to determine structure: FOURIER SYNTHESIS / Resolution: 2.3→35.25 Å / SU ML: 0.171 / Cross valid method: FREE R-VALUE / ESU R: 0.386 / ESU R Free: 0.25
RfactorNum. reflection% reflectionSelection details
Rfree0.23801 1397 5 %RANDOM
Rwork0.17471 ---
obs0.17795 26528 94.57 %-
Solvent computationIon probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.2 Å
Displacement parametersBiso mean: 35.395 Å2
Baniso -1Baniso -2Baniso -3
1--0.78 Å2-0.01 Å20.21 Å2
2--0.48 Å2-0.69 Å2
3---0.63 Å2
Refinement stepCycle: LAST / Resolution: 2.3→35.25 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms4612 0 102 385 5099
LS refinement shellResolution: 2.3→2.36 Å
RfactorNum. reflection% reflection
Rfree0.334 --
Rwork0.205 1990 -
obs--95.66 %

+
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