[English] 日本語
Yorodumi
- PDB-3kfa: Structural analysis of DFG-in and DFG-out dual Src-Abl inhibitors... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 3kfa
TitleStructural analysis of DFG-in and DFG-out dual Src-Abl inhibitors sharing a common vinyl purine template
ComponentsTyrosine-protein kinase ABL1
KeywordsTRANSFERASE / Abl / CML / drug resistance / inhibitor / ATP-binding / Kinase / Nucleotide-binding / Oncogene / Tyrosine-protein kinase
Function / homology
Function and homology information


Role of ABL in ROBO-SLIT signaling / HDR through Single Strand Annealing (SSA) / RHO GTPases Activate WASPs and WAVEs / Cyclin D associated events in G1 / Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks / protein localization to cytoplasmic microtubule plus-end / DN4 thymocyte differentiation / regulation of cellular senescence / response to epinephrine / RUNX1 regulates transcription of genes involved in differentiation of HSCs ...Role of ABL in ROBO-SLIT signaling / HDR through Single Strand Annealing (SSA) / RHO GTPases Activate WASPs and WAVEs / Cyclin D associated events in G1 / Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks / protein localization to cytoplasmic microtubule plus-end / DN4 thymocyte differentiation / regulation of cellular senescence / response to epinephrine / RUNX1 regulates transcription of genes involved in differentiation of HSCs / podocyte apoptotic process / transitional one stage B cell differentiation / regulation of modification of synaptic structure / Regulation of actin dynamics for phagocytic cup formation / delta-catenin binding / DNA conformation change / microspike assembly / neuroepithelial cell differentiation / B cell proliferation involved in immune response / positive regulation of Wnt signaling pathway, planar cell polarity pathway / positive regulation of extracellular matrix organization / cerebellum morphogenesis / regulation of extracellular matrix organization / positive regulation of blood vessel branching / circulatory system development / B-1 B cell homeostasis / neuropilin signaling pathway / neuropilin binding / Myogenesis / bubble DNA binding / activated T cell proliferation / regulation of Cdc42 protein signal transduction / proline-rich region binding / mitogen-activated protein kinase binding / positive regulation of dendrite development / syntaxin binding / myoblast proliferation / alpha-beta T cell differentiation / regulation of T cell differentiation / cardiac muscle cell proliferation / regulation of axon extension / positive regulation of cell migration involved in sprouting angiogenesis / negative regulation of cell-cell adhesion / B cell proliferation / cell leading edge / positive regulation of osteoblast proliferation / regulation of microtubule polymerization / platelet-derived growth factor receptor-beta signaling pathway / negative regulation of cellular senescence / positive regulation of focal adhesion assembly / associative learning / Bergmann glial cell differentiation / platelet-derived growth factor receptor signaling pathway / neuromuscular process controlling balance / negative regulation of mitotic cell cycle / negative regulation of long-term synaptic potentiation / negative regulation of BMP signaling pathway / negative regulation of double-strand break repair via homologous recombination / endothelial cell migration / signal transduction in response to DNA damage / positive regulation of T cell migration / BMP signaling pathway / negative regulation of endothelial cell apoptotic process / canonical NF-kappaB signal transduction / phagocytosis / positive regulation of substrate adhesion-dependent cell spreading / four-way junction DNA binding / spleen development / cellular response to transforming growth factor beta stimulus / positive regulation of vasoconstriction / positive regulation of stress fiber assembly / ruffle / positive regulation of establishment of T cell polarity / phosphotyrosine residue binding / response to endoplasmic reticulum stress / ephrin receptor binding / positive regulation of interleukin-2 production / actin filament polymerization / ERK1 and ERK2 cascade / post-embryonic development / SH2 domain binding / positive regulation of mitotic cell cycle / substrate adhesion-dependent cell spreading / thymus development / positive regulation of release of sequestered calcium ion into cytosol / integrin-mediated signaling pathway / neural tube closure / establishment of localization in cell / regulation of actin cytoskeleton organization / non-specific protein-tyrosine kinase / protein kinase C binding / B cell receptor signaling pathway / non-membrane spanning protein tyrosine kinase activity / epidermal growth factor receptor signaling pathway / neuron differentiation / negative regulation of ERK1 and ERK2 cascade / SH3 domain binding / cell-cell adhesion / peptidyl-tyrosine phosphorylation / autophagy
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 / Serine-threonine/tyrosine-protein kinase, catalytic domain / Protein tyrosine and serine/threonine kinase / Transferase(Phosphotransferase) domain 1 / Transferase(Phosphotransferase); domain 1 / Phosphorylase Kinase; domain 1 / Phosphorylase Kinase; 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-B91 / Tyrosine-protein kinase ABL1
Similarity search - Component
Biological speciesMus musculus (house mouse)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / molecular replacement / Resolution: 1.22 Å
AuthorsZhou, T.
CitationJournal: Chem.Biol.Drug Des. / Year: 2010
Title: Structural analysis of DFG-in and DFG-out dual Src-Abl inhibitors sharing a common vinyl purine template.
Authors: Zhou, T. / Commodore, L. / Huang, W.S. / Wang, Y. / Sawyer, T.K. / Shakespeare, W.C. / Clackson, T. / Zhu, X. / Dalgarno, D.C.
History
DepositionOct 27, 2009Deposition site: RCSB / Processing site: RCSB
Revision 1.0Dec 22, 2009Provider: repository / Type: Initial release
Revision 1.1Jul 13, 2011Group: Version format compliance
Revision 1.2Nov 1, 2017Group: Refinement description / Category: software
Revision 1.3Sep 6, 2023Group: Data collection / Database references ...Data collection / Database references / Derived calculations / Refinement description
Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / database_2 / pdbx_initial_refinement_model / struct_ref_seq_dif / struct_site
Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession ..._database_2.pdbx_DOI / _database_2.pdbx_database_accession / _struct_ref_seq_dif.details / _struct_site.pdbx_auth_asym_id / _struct_site.pdbx_auth_comp_id / _struct_site.pdbx_auth_seq_id

-
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)67,6014
Polymers66,4842
Non-polymers1,1172
Water14,412800
1
A: Tyrosine-protein kinase ABL1
hetero molecules


Theoretical massNumber of molelcules
Total (without water)33,8012
Polymers33,2421
Non-polymers5591
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
MethodPISA
2
B: Tyrosine-protein kinase ABL1
hetero molecules


Theoretical massNumber of molelcules
Total (without water)33,8012
Polymers33,2421
Non-polymers5591
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
MethodPISA
Unit cell
Length a, b, c (Å)43.470, 59.980, 123.550
Angle α, β, γ (deg.)90.000, 89.990, 90.000
Int Tables number4
Space group name H-MP1211

-
Components

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


Mass: 33241.965 Da / Num. of mol.: 2 / Fragment: residues 115-401
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Mus musculus (house mouse) / Gene: Abl, Abl1, c-Abl / Plasmid: pET28a / Production host: Escherichia coli (E. coli) / Strain (production host): BL21DE3
References: UniProt: P00520, non-specific protein-tyrosine kinase
#2: Chemical ChemComp-B91 / 3-{(E)-2-[6-(cyclopropylamino)-9H-purin-9-yl]ethenyl}-4-methyl-N-[3-(4-methyl-1H-imidazol-1-yl)-5-(trifluoromethyl)phenyl]benzamide


Mass: 558.557 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C29H25F3N8O
#3: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 800 / 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: 2.42 Å3/Da / Density % sol: 49.23 %
Crystal growTemperature: 277 K / Method: vapor diffusion, hanging drop / pH: 8.5
Details: 0.1 M TRIS-HCL, pH 8.5, 30% w/v PEG 4000, VAPOR DIFFUSION, HANGING DROP, temperature 277K

-
Data collection

DiffractionMean temperature: 100 K
Diffraction sourceSource: SYNCHROTRON / Site: APS / Beamline: 22-BM / Wavelength: 0.979 Å
DetectorType: MARMOSAIC 225 mm CCD / Detector: CCD / Date: Dec 1, 2007
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.979 Å / Relative weight: 1
ReflectionResolution: 1.22→50 Å / Num. all: 189032 / Num. obs: 189032 / % possible obs: 98.5 % / Observed criterion σ(F): 2 / Observed criterion σ(I): 2 / Redundancy: 3.8 % / Rmerge(I) obs: 0.055 / Net I/σ(I): 26.8
Reflection shellResolution: 1.22→1.26 Å / Redundancy: 3.2 % / Rmerge(I) obs: 0.481 / Mean I/σ(I) obs: 1.54 / Num. unique all: 16510 / % possible all: 87.8

-
Phasing

PhasingMethod: molecular replacement

-
Processing

Software
NameVersionClassificationNB
DENZOdata reduction
SCALEPACKdata scaling
AMoREphasing
CNSrefinement
PDB_EXTRACT3.005data extraction
HKL-2000data collection
HKL-2000data reduction
HKL-2000data scaling
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: PDB ENTRY 1IEP

1iep


Resolution: 1.22→50 Å / Occupancy max: 1 / Occupancy min: 1 / Cross valid method: THROUGHOUT / σ(F): 0 / Stereochemistry target values: Engh & Huber
RfactorNum. reflection% reflectionSelection details
Rfree0.201 8871 4.7 %RANDOM
Rwork0.187 ---
all0.201 188652 --
obs0.201 176375 93.5 %-
Displacement parametersBiso max: 58.21 Å2 / Biso mean: 18.666 Å2 / Biso min: 8.72 Å2
Baniso -1Baniso -2Baniso -3
1--0.017 Å20 Å20 Å2
2---0.077 Å20 Å2
3---0.094 Å2
Refinement stepCycle: LAST / Resolution: 1.22→50 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms4604 0 82 800 5486
Refine LS restraints
Refine-IDTypeDev idealDev ideal target
X-RAY DIFFRACTIONc_mcbond_it1.0271.5
X-RAY DIFFRACTIONc_scbond_it2.0312
X-RAY DIFFRACTIONc_mcangle_it1.5512
X-RAY DIFFRACTIONc_scangle_it2.9962.5
Xplor file
Refine-IDSerial noParam file
X-RAY DIFFRACTION1protein_rep.param
X-RAY DIFFRACTION2dna-rna_rep.param
X-RAY DIFFRACTION3water_rep.param
X-RAY DIFFRACTION4ion.param
X-RAY DIFFRACTION5AP24163_r2_B.param

+
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