[English] 日本語
Yorodumi
- PDB-7cc2: Strategic design of catalytic lysine-targeting reversible covalen... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 7cc2
TitleStrategic design of catalytic lysine-targeting reversible covalent BCR-ABL Inhibitors
ComponentsTyrosine-protein kinase ABL1
KeywordsTRANSFERASE / Tyrosine kinase Covalent inhibitor chronic myelogenous leukemia
Function / homology
Function and homology information


: / positive regulation of actin filament binding / positive regulation of oxidoreductase activity / protein localization to cytoplasmic microtubule plus-end / DNA conformation change / podocyte apoptotic process / DN4 thymocyte differentiation / Role of ABL in ROBO-SLIT signaling / response to epinephrine / transitional one stage B cell differentiation ...: / positive regulation of actin filament binding / positive regulation of oxidoreductase activity / protein localization to cytoplasmic microtubule plus-end / DNA conformation change / podocyte apoptotic process / DN4 thymocyte differentiation / Role of ABL in ROBO-SLIT signaling / response to epinephrine / transitional one stage B cell differentiation / activation of protein kinase C activity / nicotinate-nucleotide adenylyltransferase activity / regulation of modification of synaptic structure / positive regulation of microtubule binding / delta-catenin binding / B cell proliferation involved in immune response / positive regulation of extracellular matrix organization / neuroepithelial cell differentiation / microspike assembly / positive regulation of Wnt signaling pathway, planar cell polarity pathway / cerebellum morphogenesis / positive regulation of blood vessel branching / B-1 B cell homeostasis / mitochondrial depolarization / negative regulation of ubiquitin-protein transferase activity / neuropilin signaling pathway / neuropilin binding / bubble DNA binding / negative regulation of protein serine/threonine kinase activity / activated T cell proliferation / cellular response to dopamine / regulation of cell motility / regulation of Cdc42 protein signal transduction / proline-rich region binding / positive regulation of dendrite development / mitogen-activated protein kinase binding / myoblast proliferation / regulation of hematopoietic stem cell differentiation / syntaxin binding / alpha-beta T cell differentiation / cardiac muscle cell proliferation / regulation of T cell differentiation / regulation of axon extension / HDR through Single Strand Annealing (SSA) / positive regulation of cell migration involved in sprouting angiogenesis / negative regulation of cell-cell adhesion / Fc-gamma receptor signaling pathway involved in phagocytosis / Myogenesis / regulation of microtubule polymerization / positive regulation of osteoblast proliferation / RUNX2 regulates osteoblast differentiation / 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 / neuromuscular process controlling balance / regulation of endocytosis / negative regulation of BMP signaling pathway / negative regulation of mitotic cell cycle / negative regulation of long-term synaptic potentiation / actin monomer binding / endothelial cell migration / RHO GTPases Activate WASPs and WAVEs / positive regulation of T cell migration / canonical NF-kappaB signal transduction / signal transduction in response to DNA damage / negative regulation of double-strand break repair via homologous recombination / regulation of cell adhesion / BMP signaling pathway / mismatch repair / negative regulation of endothelial cell apoptotic process / four-way junction DNA binding / peptidyl-tyrosine autophosphorylation / positive regulation of substrate adhesion-dependent cell spreading / positive regulation of vasoconstriction / spleen development / positive regulation of stress fiber assembly / cellular response to transforming growth factor beta stimulus / ruffle / positive regulation of establishment of T cell polarity / ERK1 and ERK2 cascade / positive regulation of interleukin-2 production / ephrin receptor binding / actin filament polymerization / phosphotyrosine residue binding / positive regulation of endothelial cell migration / response to endoplasmic reticulum stress / positive regulation of mitotic cell cycle / SH2 domain binding / substrate adhesion-dependent cell spreading / positive regulation of release of sequestered calcium ion into cytosol / post-embryonic development / thymus development / regulation of autophagy / neural tube closure / establishment of localization in cell / integrin-mediated signaling pathway / regulation of actin cytoskeleton organization / protein kinase C binding
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 / Src homology 3 domains ...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 / Protein kinase, ATP binding site / Protein kinases ATP-binding region signature. / Protein kinase domain profile. / Protein kinase domain / Protein kinase-like domain superfamily
Similarity search - Domain/homology
Chem-FVC / Tyrosine-protein kinase ABL1
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.723 Å
AuthorsAnantharajan, J. / Baburajendran, N.
Funding support Singapore, 1items
OrganizationGrant numberCountry
National Medical Research Council Singapore
CitationJournal: Angew.Chem.Int.Ed.Engl. / Year: 2021
Title: Strategic Design of Catalytic Lysine-Targeting Reversible Covalent BCR-ABL Inhibitors*.
Authors: Quach, D. / Tang, G. / Anantharajan, J. / Baburajendran, N. / Poulsen, A. / Wee, J.L.K. / Retna, P. / Li, R. / Liu, B. / Tee, D.H.Y. / Kwek, P.Z. / Joy, J.K. / Yang, W.Q. / Zhang, C.J. / ...Authors: Quach, D. / Tang, G. / Anantharajan, J. / Baburajendran, N. / Poulsen, A. / Wee, J.L.K. / Retna, P. / Li, R. / Liu, B. / Tee, D.H.Y. / Kwek, P.Z. / Joy, J.K. / Yang, W.Q. / Zhang, C.J. / Foo, K. / Keller, T.H. / Yao, S.Q.
History
DepositionJun 16, 2020Deposition site: PDBJ / Processing site: PDBJ
Revision 1.0Jun 9, 2021Provider: repository / Type: Initial release
Revision 1.1Jul 28, 2021Group: 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 1.2Nov 29, 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 / struct_ncs_dom_lim
Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession ..._database_2.pdbx_DOI / _database_2.pdbx_database_accession / _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: Tyrosine-protein kinase ABL1
B: Tyrosine-protein kinase ABL1
hetero molecules


Theoretical massNumber of molelcules
Total (without water)72,5904
Polymers71,7902
Non-polymers8002
Water81145
1
A: Tyrosine-protein kinase ABL1
hetero molecules


Theoretical massNumber of molelcules
Total (without water)36,2952
Polymers35,8951
Non-polymers4001
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
2
B: Tyrosine-protein kinase ABL1
hetero molecules


Theoretical massNumber of molelcules
Total (without water)36,2952
Polymers35,8951
Non-polymers4001
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Unit cell
Length a, b, c (Å)116.489, 127.939, 56.760
Angle α, β, γ (deg.)90.000, 90.000, 90.000
Int Tables number18
Space group name H-MP21212
Noncrystallographic symmetry (NCS)NCS domain:
IDEns-IDDetails
11(chain A and (resid 233 through 237 or (resid 238...
21(chain B and (resid 233 through 248 or resid 255...

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
11ASPASPMETMET(chain A and (resid 233 through 237 or (resid 238...AA233 - 23733 - 37
12GLUGLUGLUGLU(chain A and (resid 233 through 237 or (resid 238...AA23838
13ASPASPSERSER(chain A and (resid 233 through 237 or (resid 238...AA233 - 50133 - 301
14ASPASPSERSER(chain A and (resid 233 through 237 or (resid 238...AA233 - 50133 - 301
15ASPASPSERSER(chain A and (resid 233 through 237 or (resid 238...AA233 - 50133 - 301
16ASPASPSERSER(chain A and (resid 233 through 237 or (resid 238...AA233 - 50133 - 301
21ASPASPLEULEU(chain B and (resid 233 through 248 or resid 255...BB233 - 24833 - 48
22GLUGLUTHRTHR(chain B and (resid 233 through 248 or resid 255...BB255 - 27755 - 77
23METMETPHEPHE(chain B and (resid 233 through 248 or resid 255...BB278 - 28378 - 83
24TYRTYRSERSER(chain B and (resid 233 through 248 or resid 255...BB232 - 50132 - 301
25TYRTYRSERSER(chain B and (resid 233 through 248 or resid 255...BB232 - 50132 - 301
26TYRTYRSERSER(chain B and (resid 233 through 248 or resid 255...BB232 - 50132 - 301
27TYRTYRSERSER(chain B and (resid 233 through 248 or resid 255...BB232 - 50132 - 301
28TYRTYRSERSER(chain B and (resid 233 through 248 or resid 255...BB232 - 50132 - 301

-
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: 35894.848 Da / Num. of mol.: 2
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: ABL1, ABL, JTK7 / Production host: Escherichia coli (E. coli)
References: UniProt: P00519, non-specific protein-tyrosine kinase
#2: Chemical ChemComp-FVC / [4-[5-[5-(dimethylcarbamoyl)pyridin-3-yl]-1H-pyrrolo[2,3-b]pyridin-3-yl]-2-methyl-phenyl]boronic acid


Mass: 400.238 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C22H21BN4O3
#3: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 45 / 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: 2.93 Å3/Da / Density % sol: 57.98 %
Crystal growTemperature: 277.15 K / Method: vapor diffusion, hanging drop
Details: 7 % w/v Polyethylene glycol 8000, 100 mM MES pH 6.5, 20 % v/v Ethylene glycol

-
Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: Australian Synchrotron / Beamline: MX2 / Wavelength: 0.95374 Å
DetectorType: ADSC QUANTUM 315r / Detector: CCD / Date: Oct 28, 2018
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.95374 Å / Relative weight: 1
ReflectionResolution: 2.72→47.395 Å / Num. obs: 23393 / % possible obs: 99.5 % / Redundancy: 6.7 % / Biso Wilson estimate: 43.73 Å2 / CC1/2: 0.995 / Rmerge(I) obs: 0.144 / Rpim(I) all: 0.06 / Rrim(I) all: 0.157 / Net I/σ(I): 8.7
Reflection shell

Diffraction-ID: 1

Resolution (Å)Redundancy (%)Rmerge(I) obsNum. unique obsCC1/2Rpim(I) allRrim(I) all% possible all
2.72-2.856.80.75330000.7850.3070.81597.6
9.02-47.3956.20.0417240.9990.0170.04498.5

-
Processing

Software
NameVersionClassification
PHENIX1.11.1_2575refinement
Aimless0.7.2data scaling
PDB_EXTRACT3.25data extraction
XDSdata reduction
PHASERphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 2QOH

2qoh


Resolution: 2.723→47.39 Å / SU ML: 0.33 / Cross valid method: THROUGHOUT / σ(F): 1.36 / Phase error: 22.53 / Stereochemistry target values: ML
RfactorNum. reflection% reflection
Rfree0.2418 2000 8.57 %
Rwork0.1922 21343 -
obs0.1964 23343 99.61 %
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT BULK SOLVENT MODEL
Displacement parametersBiso max: 129.3 Å2 / Biso mean: 46.1251 Å2 / Biso min: 13.4 Å2
Refinement stepCycle: final / Resolution: 2.723→47.39 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms4303 0 0 45 4348
Biso mean---34.99 -
Num. residues----529
Refine LS restraints
Refine-IDTypeDev idealNumber
X-RAY DIFFRACTIONf_bond_d0.0034418
X-RAY DIFFRACTIONf_angle_d0.6765985
X-RAY DIFFRACTIONf_chiral_restr0.045643
X-RAY DIFFRACTIONf_plane_restr0.003746
X-RAY DIFFRACTIONf_dihedral_angle_d5.4942596
Refine LS restraints NCS
Ens-IDDom-IDAuth asym-IDNumberRefine-IDRmsType
11A2398X-RAY DIFFRACTION8.779TORSIONAL
12B2398X-RAY DIFFRACTION8.779TORSIONAL
LS refinement shell

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

Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection Rwork% reflection obs (%)
2.723-2.7910.35551380.2615147399
2.791-2.86640.31211400.229148899
2.8664-2.95070.29861410.21521515100
2.9507-3.0460.28431400.22111493100
3.046-3.15480.24961420.20151512100
3.1548-3.28110.31521400.20511502100
3.2811-3.43040.23781420.20061507100
3.4304-3.61120.211420.18171517100
3.6112-3.83730.23431420.1861514100
3.8373-4.13350.22891430.17441532100
4.1335-4.54910.1861440.1671528100
4.5491-5.20670.19861450.16841563100
5.2067-6.55710.23371470.20471558100
6.5571-47.390.26591540.1943164199

+
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://pdbjlvh1.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