[English] 日本語
Yorodumi
- PDB-6e6e: DGY-06-116, a novel and selective covalent inhibitor of SRC kinase -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 6e6e
TitleDGY-06-116, a novel and selective covalent inhibitor of SRC kinase
ComponentsProto-oncogene tyrosine-protein kinase Src
KeywordsTRANSFERASE/TRANSFERASE inhibitor / PROTO-ONCOGENE TYROSINE-PROTEIN KINASE SRC / TRANSFERASE / TRANSFERASE-TRANSFERASE inhibitor complex
Function / homology
Function and homology information


regulation of caveolin-mediated endocytosis / regulation of toll-like receptor 3 signaling pathway / positive regulation of platelet-derived growth factor receptor-beta signaling pathway / cellular response to progesterone stimulus / positive regulation of dephosphorylation / regulation of cell projection assembly / negative regulation of telomere maintenance / Regulation of commissural axon pathfinding by SLIT and ROBO / regulation of epithelial cell migration / ERBB2 signaling pathway ...regulation of caveolin-mediated endocytosis / regulation of toll-like receptor 3 signaling pathway / positive regulation of platelet-derived growth factor receptor-beta signaling pathway / cellular response to progesterone stimulus / positive regulation of dephosphorylation / regulation of cell projection assembly / negative regulation of telomere maintenance / Regulation of commissural axon pathfinding by SLIT and ROBO / regulation of epithelial cell migration / ERBB2 signaling pathway / Regulation of gap junction activity / BMP receptor binding / negative regulation of focal adhesion assembly / positive regulation of integrin activation / Activated NTRK2 signals through FYN / positive regulation of protein processing / Netrin mediated repulsion signals / regulation of intracellular estrogen receptor signaling pathway / intestinal epithelial cell development / negative regulation of neutrophil activation / regulation of vascular permeability / focal adhesion assembly / osteoclast development / connexin binding / Activated NTRK3 signals through PI3K / cellular response to fluid shear stress / signal complex assembly / positive regulation of small GTPase mediated signal transduction / branching involved in mammary gland duct morphogenesis / Co-stimulation by CD28 / Regulation of RUNX1 Expression and Activity / DCC mediated attractive signaling / EPH-Ephrin signaling / positive regulation of podosome assembly / regulation of bone resorption / positive regulation of lamellipodium morphogenesis / Ephrin signaling / Signal regulatory protein family interactions / podosome / odontogenesis / negative regulation of mitochondrial depolarization / MET activates PTK2 signaling / cellular response to peptide hormone stimulus / Regulation of KIT signaling / regulation of early endosome to late endosome transport / leukocyte migration / Signaling by ALK / phospholipase activator activity / oogenesis / GP1b-IX-V activation signalling / Co-inhibition by CTLA4 / EPHA-mediated growth cone collapse / Receptor Mediated Mitophagy / p130Cas linkage to MAPK signaling for integrins / interleukin-6-mediated signaling pathway / stress fiber assembly / positive regulation of Notch signaling pathway / Signaling by EGFR / RUNX2 regulates osteoblast differentiation / stimulatory C-type lectin receptor signaling pathway / negative regulation of intrinsic apoptotic signaling pathway / Fc-gamma receptor signaling pathway involved in phagocytosis / regulation of cell-cell adhesion / Recycling pathway of L1 / PECAM1 interactions / uterus development / regulation of heart rate by cardiac conduction / GRB2:SOS provides linkage to MAPK signaling for Integrins / RHOU GTPase cycle / protein tyrosine kinase activator activity / negative regulation of anoikis / signaling receptor activator activity / RET signaling / Long-term potentiation / FCGR activation / positive regulation of epithelial cell migration / EPH-ephrin mediated repulsion of cells / positive regulation of protein serine/threonine kinase activity / GAB1 signalosome / negative regulation of hippo signaling / vascular endothelial growth factor receptor signaling pathway / ephrin receptor signaling pathway / bone resorption / negative regulation of protein-containing complex assembly / forebrain development / progesterone receptor signaling pathway / Nuclear signaling by ERBB4 / phospholipase binding / T cell costimulation / cellular response to platelet-derived growth factor stimulus / p38MAPK events / ephrin receptor binding / Signaling by ERBB2 / EPHB-mediated forward signaling / Integrin signaling / ionotropic glutamate receptor binding / positive regulation of TORC1 signaling / NCAM signaling for neurite out-growth / substrate adhesion-dependent cell spreading / Downstream signal transduction
Similarity search - Function
: / 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 / 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 / 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-HVY / Proto-oncogene tyrosine-protein kinase Src
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.15 Å
AuthorsGurbani, D. / Bera, A. / Westover, K.
CitationJournal: Front Mol Biosci / Year: 2020
Title: Structure and Characterization of a Covalent Inhibitor of Src Kinase.
Authors: Gurbani, D. / Du, G. / Henning, N.J. / Rao, S. / Bera, A.K. / Zhang, T. / Gray, N.S. / Westover, K.D.
History
DepositionJul 24, 2018Deposition site: RCSB / Processing site: RCSB
Revision 1.0Jul 31, 2019Provider: repository / Type: Initial release
Revision 2.0Dec 11, 2019Group: Advisory / Atomic model ...Advisory / Atomic model / Data collection / Database references / Derived calculations / Structure summary
Category: atom_site / pdbx_poly_seq_scheme ...atom_site / pdbx_poly_seq_scheme / pdbx_struct_sheet_hbond / pdbx_unobs_or_zero_occ_residues / pdbx_validate_torsion / struct_conf / struct_conn / struct_mon_prot_cis / struct_ref_seq / struct_sheet_range / struct_site_gen
Item: _atom_site.auth_seq_id / _pdbx_poly_seq_scheme.pdb_seq_num ..._atom_site.auth_seq_id / _pdbx_poly_seq_scheme.pdb_seq_num / _pdbx_struct_sheet_hbond.range_1_auth_seq_id / _pdbx_struct_sheet_hbond.range_2_auth_seq_id / _pdbx_unobs_or_zero_occ_residues.auth_seq_id / _pdbx_validate_torsion.auth_seq_id / _struct_conf.beg_auth_seq_id / _struct_conf.end_auth_seq_id / _struct_conn.ptnr1_auth_seq_id / _struct_mon_prot_cis.auth_seq_id / _struct_mon_prot_cis.pdbx_auth_seq_id_2 / _struct_ref_seq.pdbx_auth_seq_align_beg / _struct_ref_seq.pdbx_auth_seq_align_end / _struct_sheet_range.beg_auth_seq_id / _struct_sheet_range.end_auth_seq_id / _struct_site_gen.auth_seq_id
Revision 2.1Jun 24, 2020Group: Database references / Category: citation / citation_author
Item: _citation.country / _citation.journal_abbrev ..._citation.country / _citation.journal_abbrev / _citation.journal_id_CSD / _citation.journal_id_ISSN / _citation.journal_volume / _citation.page_first / _citation.page_last / _citation.pdbx_database_id_DOI / _citation.pdbx_database_id_PubMed / _citation.title / _citation.year
Revision 2.2Oct 11, 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
Revision 2.3Nov 6, 2024Group: Structure summary / Category: pdbx_entry_details / pdbx_modification_feature

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Proto-oncogene tyrosine-protein kinase Src
B: Proto-oncogene tyrosine-protein kinase Src
C: Proto-oncogene tyrosine-protein kinase Src
D: Proto-oncogene tyrosine-protein kinase Src
E: Proto-oncogene tyrosine-protein kinase Src
F: Proto-oncogene tyrosine-protein kinase Src
G: Proto-oncogene tyrosine-protein kinase Src
H: Proto-oncogene tyrosine-protein kinase Src
hetero molecules


Theoretical massNumber of molelcules
Total (without water)258,04416
Polymers253,2518
Non-polymers4,7938
Water7,837435
1
A: Proto-oncogene tyrosine-protein kinase Src
hetero molecules


Theoretical massNumber of molelcules
Total (without water)32,2552
Polymers31,6561
Non-polymers5991
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
MethodPISA
2
B: Proto-oncogene tyrosine-protein kinase Src
hetero molecules


Theoretical massNumber of molelcules
Total (without water)32,2552
Polymers31,6561
Non-polymers5991
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
MethodPISA
3
C: Proto-oncogene tyrosine-protein kinase Src
hetero molecules


Theoretical massNumber of molelcules
Total (without water)32,2552
Polymers31,6561
Non-polymers5991
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
MethodPISA
4
D: Proto-oncogene tyrosine-protein kinase Src
hetero molecules


Theoretical massNumber of molelcules
Total (without water)32,2552
Polymers31,6561
Non-polymers5991
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
MethodPISA
5
E: Proto-oncogene tyrosine-protein kinase Src
hetero molecules


Theoretical massNumber of molelcules
Total (without water)32,2552
Polymers31,6561
Non-polymers5991
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
MethodPISA
6
F: Proto-oncogene tyrosine-protein kinase Src
hetero molecules


Theoretical massNumber of molelcules
Total (without water)32,2552
Polymers31,6561
Non-polymers5991
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
MethodPISA
7
G: Proto-oncogene tyrosine-protein kinase Src
hetero molecules


Theoretical massNumber of molelcules
Total (without water)32,2552
Polymers31,6561
Non-polymers5991
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
MethodPISA
8
H: Proto-oncogene tyrosine-protein kinase Src
hetero molecules


Theoretical massNumber of molelcules
Total (without water)32,2552
Polymers31,6561
Non-polymers5991
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
MethodPISA
Unit cell
Length a, b, c (Å)63.534, 84.028, 120.109
Angle α, β, γ (deg.)89.962, 90.046, 90.118
Int Tables number1
Space group name H-MP1
Space group name HallP1

-
Components

#1: Protein
Proto-oncogene tyrosine-protein kinase Src / Proto-oncogene c-Src / pp60c-src / p60-Src


Mass: 31656.355 Da / Num. of mol.: 8
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: SRC, SRC1 / Production host: Escherichia coli (E. coli)
References: UniProt: P12931, non-specific protein-tyrosine kinase
#2: Chemical
ChemComp-HVY / N-(2-chloro-6-methylphenyl)-2-{[4-(4-methylpiperazin-1-yl)phenyl]amino}-4-{[2-(propanoylamino)phenyl]amino}pyrimidine-5-carboxamide


Mass: 599.126 Da / Num. of mol.: 8 / Source method: obtained synthetically / Formula: C32H35ClN8O2
#3: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 435 / Source method: isolated from a natural source / Formula: H2O
Has protein modificationY

-
Experimental details

-
Experiment

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

-
Sample preparation

CrystalDensity Matthews: 2.53 Å3/Da / Density % sol: 51.44 %
Crystal growTemperature: 293 K / Method: vapor diffusion, sitting drop / pH: 7.5 / Details: 0.1M Magnesium Formate Dihydrate; 15% PEG3350

-
Data collection

DiffractionMean temperature: 100 K
Diffraction sourceSource: SYNCHROTRON / Site: APS / Beamline: 19-ID / Wavelength: 0.97951 Å
DetectorType: DECTRIS PILATUS 6M-F / Detector: PIXEL / Date: Jun 14, 2018
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.97951 Å / Relative weight: 1
ReflectionResolution: 2.15→50 Å / Num. obs: 123213 / % possible obs: 91.7 % / Redundancy: 3.6 % / Biso Wilson estimate: 36.4 Å2 / Rmerge(I) obs: 0.127 / Rpim(I) all: 0.076 / Net I/σ(I): 9.68
Reflection shellResolution: 2.15→2.19 Å / Redundancy: 3 % / Rmerge(I) obs: 0.964 / Num. unique obs: 6186 / % possible all: 91.6

-
Processing

Software
NameVersionClassification
PHENIX1.14rc3_3199refinement
PDB_EXTRACT3.24data extraction
HKL-3000data reduction
SCALEPACKdata scaling
PHASERphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 4MXO

4mxo


Resolution: 2.15→43.66 Å / SU ML: 0.34 / Cross valid method: THROUGHOUT / σ(F): 1.96 / Phase error: 36.3411
RfactorNum. reflection% reflection
Rfree0.2849 5955 4.86 %
Rwork0.2499 --
obs0.2517 122649 90.78 %
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å
Displacement parametersBiso mean: 46.64 Å2
Refinement stepCycle: LAST / Resolution: 2.15→43.66 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms17436 0 0 435 17871
Refine LS restraints
Refine-IDTypeDev idealNumber
X-RAY DIFFRACTIONf_bond_d0.002217948
X-RAY DIFFRACTIONf_angle_d0.592324343
X-RAY DIFFRACTIONf_chiral_restr0.04062571
X-RAY DIFFRACTIONf_plane_restr0.0043112
X-RAY DIFFRACTIONf_dihedral_angle_d14.47510968
LS refinement shell
Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkRefine-ID% reflection obs (%)
2.15-2.170.33521620.333168X-RAY DIFFRACTION75.44
2.17-2.20.40132030.33233953X-RAY DIFFRACTION91.28
2.2-2.230.31281730.32983968X-RAY DIFFRACTION91.9
2.23-2.250.37912080.33173925X-RAY DIFFRACTION91.64
2.25-2.280.35961580.31373958X-RAY DIFFRACTION91.26
2.28-2.320.32461640.31443905X-RAY DIFFRACTION91.62
2.32-2.350.35071970.30224007X-RAY DIFFRACTION90.94
2.35-2.380.39891730.30573802X-RAY DIFFRACTION89.55
2.38-2.420.33941950.29373819X-RAY DIFFRACTION89.16
2.42-2.460.35752060.28223728X-RAY DIFFRACTION86.69
2.46-2.50.36421900.27453400X-RAY DIFFRACTION80.13
2.5-2.550.28951810.26864036X-RAY DIFFRACTION93.34
2.55-2.60.3271800.27764009X-RAY DIFFRACTION94.69
2.6-2.650.34031920.28624146X-RAY DIFFRACTION94.37
2.65-2.710.32232130.26634028X-RAY DIFFRACTION94.12
2.71-2.770.32372550.25143980X-RAY DIFFRACTION93.84
2.77-2.840.32792280.25743927X-RAY DIFFRACTION93.56
2.84-2.920.34492080.26264012X-RAY DIFFRACTION92.81
2.92-30.29132400.26483919X-RAY DIFFRACTION91.77
3-3.10.31441880.26443859X-RAY DIFFRACTION90.74
3.1-3.210.29332180.26083626X-RAY DIFFRACTION85.59
3.21-3.340.24092040.24843819X-RAY DIFFRACTION88.83
3.34-3.490.27522240.23594086X-RAY DIFFRACTION95.65
3.49-3.680.3161890.23174083X-RAY DIFFRACTION95.59
3.68-3.910.24271960.23434128X-RAY DIFFRACTION95.03
3.91-4.210.26342270.21724015X-RAY DIFFRACTION93.77
4.21-4.630.19971560.20543856X-RAY DIFFRACTION90.24
4.63-5.30.26131720.20853942X-RAY DIFFRACTION90.38
5.3-6.670.28142650.24254035X-RAY DIFFRACTION96.22
6.67-43.670.21171900.22713555X-RAY DIFFRACTION83.24

+
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