[English] 日本語
Yorodumi
- PDB-2qlq: Crystal structure of SRC kinase domain with covalent inhibitor RL3 -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 2qlq
TitleCrystal structure of SRC kinase domain with covalent inhibitor RL3
ComponentsProto-oncogene tyrosine-protein kinase Src
KeywordsTRANSFERASE / Src kinase domain / drug resistance / irreversible inhibitor / kovalent inhibitor / Alternative splicing / ATP-binding / Lipoprotein / Myristate / Nucleotide-binding / Phosphorylation / Proto-oncogene / SH2 domain / SH3 domain / Tyrosine-protein kinase
Function / homology
Function and homology information


Signaling by ERBB2 / Nuclear signaling by ERBB4 / PIP3 activates AKT signaling / Signaling by SCF-KIT / Regulation of KIT signaling / Signaling by EGFR / GAB1 signalosome / Regulation of gap junction activity / FCGR activation / PECAM1 interactions ...Signaling by ERBB2 / Nuclear signaling by ERBB4 / PIP3 activates AKT signaling / Signaling by SCF-KIT / Regulation of KIT signaling / Signaling by EGFR / GAB1 signalosome / Regulation of gap junction activity / FCGR activation / PECAM1 interactions / CD28 co-stimulation / CTLA4 inhibitory signaling / EPHA-mediated growth cone collapse / Ephrin signaling / G alpha (i) signalling events / GP1b-IX-V activation signalling / Recycling pathway of L1 / Thrombin signalling through proteinase activated receptors (PARs) / VEGFR2 mediated cell proliferation / RAF activation / PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling / RET signaling / Receptor Mediated Mitophagy / ADP signalling through P2Y purinoceptor 1 / Downregulation of ERBB4 signaling / EPH-ephrin mediated repulsion of cells / Cyclin D associated events in G1 / Regulation of RUNX3 expression and activity / Activated NTRK3 signals through PI3K / Downstream signal transduction / MAP2K and MAPK activation / Integrin signaling / GRB2:SOS provides linkage to MAPK signaling for Integrins / MET activates PTK2 signaling / Extra-nuclear estrogen signaling / EPHB-mediated forward signaling / p130Cas linkage to MAPK signaling for integrins / VEGFA-VEGFR2 Pathway / connexin binding / osteoclast development / progesterone receptor signaling pathway / negative regulation of intrinsic apoptotic signaling pathway / bone resorption / extrinsic component of cytoplasmic side of plasma membrane / negative regulation of extrinsic apoptotic signaling pathway / non-specific protein-tyrosine kinase / non-membrane spanning protein tyrosine kinase activity / epidermal growth factor receptor signaling pathway / cell junction / protein phosphatase binding / protein tyrosine kinase activity / mitochondrial inner membrane / cell differentiation / cytoskeleton / endosome membrane / regulation of cell cycle / cell adhesion / cell cycle / phosphorylation / signaling receptor binding / focal adhesion / innate immune response / heme binding / perinuclear region of cytoplasm / protein-containing complex / ATP binding / membrane / nucleus / plasma membrane / cytosol
Similarity search - Function
SH3 domain / SH2 domain / Src homology 2 (SH2) domain profile. / Src homology 2 domains / Src homology 3 domains / SH2 domain / SH2 domain superfamily / SH3-like domain superfamily / Src homology 3 (SH3) domain profile. / SH3 domain ...SH3 domain / SH2 domain / Src homology 2 (SH2) domain profile. / Src homology 2 domains / Src homology 3 domains / SH2 domain / 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 / 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-SR2 / Proto-oncogene tyrosine-protein kinase Src
Similarity search - Component
Biological speciesGallus gallus (chicken)
MethodX-RAY DIFFRACTION / MOLECULAR REPLACEMENT / Resolution: 2.33 Å
AuthorsMichalczyk, A. / Rode, H.B. / Gruetter, C. / Rauh, D.
CitationJournal: Bioorg.Med.Chem. / Year: 2008
Title: Structural insights into how irreversible inhibitors can overcome drug resistance in EGFR.
Authors: Michalczyk, A. / Kluter, S. / Rode, H.B. / Simard, J.R. / Grutter, C. / Rabiller, M. / Rauh, D.
History
DepositionJul 13, 2007Deposition site: RCSB / Processing site: RCSB
Revision 1.0Mar 11, 2008Provider: repository / Type: Initial release
Revision 1.1Jul 13, 2011Group: Version format compliance
Revision 1.2Oct 20, 2021Group: Database references / Derived calculations
Category: database_2 / struct_conn ...database_2 / struct_conn / 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_conn.pdbx_leaving_atom_flag / _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: Proto-oncogene tyrosine-protein kinase Src
B: Proto-oncogene tyrosine-protein kinase Src
hetero molecules


Theoretical massNumber of molelcules
Total (without water)66,7645
Polymers65,4852
Non-polymers1,2793
Water1,78399
1
A: Proto-oncogene tyrosine-protein kinase Src
hetero molecules


Theoretical massNumber of molelcules
Total (without water)33,5953
Polymers32,7431
Non-polymers8532
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)33,1692
Polymers32,7431
Non-polymers4261
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
MethodPISA
Unit cell
Length a, b, c (Å)41.940, 63.530, 74.500
Angle α, β, γ (deg.)78.28, 90.37, 89.45
Int Tables number1
Space group name H-MP1

-
Components

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


Mass: 32742.711 Da / Num. of mol.: 2 / Fragment: Protein kinase domain / Mutation: S345C
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Gallus gallus (chicken) / Gene: SRC / Plasmid: pSKB3 / Species (production host): Escherichia coli / Production host: Escherichia coli BL21(DE3) (bacteria) / Strain (production host): BL21(DE3)
References: UniProt: P00523, non-specific protein-tyrosine kinase
#2: Chemical ChemComp-SR2 / (2E)-N-{4-[(3-bromophenyl)amino]quinazolin-6-yl}-4-(dimethylamino)but-2-enamide


Mass: 426.310 Da / Num. of mol.: 3 / Source method: obtained synthetically / Formula: C20H20BrN5O
#3: Water ChemComp-HOH / water / Water


Mass: 18.015 Da / Num. of mol.: 99 / 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: 2.97 Å3/Da / Density % sol: 58.55 %
Crystal growTemperature: 298 K / Method: vapor diffusion, hanging drop / pH: 8
Details: 16% Ethylene glycol, pH 8.0, VAPOR DIFFUSION, HANGING DROP, temperature 298K

-
Data collection

DiffractionMean temperature: 100 K
Diffraction sourceSource: ROTATING ANODE / Type: RIGAKU MICROMAX-007 / Wavelength: 1.5417 Å
DetectorType: MAR scanner 345 mm plate / Detector: IMAGE PLATE / Date: Dec 13, 2006
RadiationMonochromator: Multilayer Optic (Osmic) / Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1.5417 Å / Relative weight: 1
ReflectionResolution: 2.33→72.944 Å / Num. all: 32156 / Num. obs: 29166 / % possible obs: 90.7 % / Redundancy: 3.7 % / Rmerge(I) obs: 0.06 / Rsym value: 0.06 / Net I/σ(I): 11.6
Reflection shell
Resolution (Å)Redundancy (%)Rmerge(I) obsMean I/σ(I) obsRsym value% possible all
2.33-2.463.60.4071.80.40785.9
2.46-2.613.60.292.60.2989.2
2.61-2.783.70.1973.80.19790.2
2.78-3.013.80.12660.12691.1
3.01-3.33.80.0819.30.08191.8
3.3-3.683.80.04715.80.04792.3
3.68-4.253.80.03123.30.03192.6
4.25-5.213.80.02625.50.02693.6
5.21-7.373.80.02726.30.02793.6
7.37-52.943.80.02221.20.02293.8

-
Processing

Software
NameVersionClassificationNB
SCALAdata scaling
REFMACrefinement
PDB_EXTRACT2data extraction
MAR345dtbdata collection
MOSFLMdata reduction
PHASERphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT / Resolution: 2.33→72.93 Å / Cor.coef. Fo:Fc: 0.926 / Cor.coef. Fo:Fc free: 0.88 / SU B: 6.714 / SU ML: 0.168 / Cross valid method: THROUGHOUT / ESU R: 0.312 / ESU R Free: 0.251 / Stereochemistry target values: MAXIMUM LIKELIHOOD / Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS
RfactorNum. reflection% reflectionSelection details
Rfree0.26673 1463 5 %RANDOM
Rwork0.2123 ---
obs0.21508 27702 90.72 %-
all-32683 --
Solvent computationIon probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.4 Å / Solvent model: MASK
Displacement parametersBiso mean: 32.043 Å2
Baniso -1Baniso -2Baniso -3
1-0.06 Å2-0.08 Å20.17 Å2
2---0.44 Å20.82 Å2
3---0.05 Å2
Refinement stepCycle: LAST / Resolution: 2.33→72.93 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms3892 0 93 99 4084
Refine LS restraints
Refine-IDTypeDev idealDev ideal targetNumber
X-RAY DIFFRACTIONr_bond_refined_d0.0160.0224096
X-RAY DIFFRACTIONr_bond_other_d
X-RAY DIFFRACTIONr_angle_refined_deg1.771.9995566
X-RAY DIFFRACTIONr_angle_other_deg
X-RAY DIFFRACTIONr_dihedral_angle_1_deg9.7035492
X-RAY DIFFRACTIONr_dihedral_angle_2_deg37.58123.873173
X-RAY DIFFRACTIONr_dihedral_angle_3_deg17.75415672
X-RAY DIFFRACTIONr_dihedral_angle_4_deg16.8771525
X-RAY DIFFRACTIONr_chiral_restr0.1240.2602
X-RAY DIFFRACTIONr_gen_planes_refined0.0060.023103
X-RAY DIFFRACTIONr_gen_planes_other
X-RAY DIFFRACTIONr_nbd_refined0.2190.21909
X-RAY DIFFRACTIONr_nbd_other
X-RAY DIFFRACTIONr_nbtor_refined0.3090.22705
X-RAY DIFFRACTIONr_nbtor_other
X-RAY DIFFRACTIONr_xyhbond_nbd_refined0.1750.2171
X-RAY DIFFRACTIONr_xyhbond_nbd_other
X-RAY DIFFRACTIONr_metal_ion_refined
X-RAY DIFFRACTIONr_metal_ion_other
X-RAY DIFFRACTIONr_symmetry_vdw_refined0.2420.241
X-RAY DIFFRACTIONr_symmetry_vdw_other
X-RAY DIFFRACTIONr_symmetry_hbond_refined0.3290.27
X-RAY DIFFRACTIONr_symmetry_hbond_other
X-RAY DIFFRACTIONr_symmetry_metal_ion_refined
X-RAY DIFFRACTIONr_symmetry_metal_ion_other
X-RAY DIFFRACTIONr_mcbond_it0.961.52541
X-RAY DIFFRACTIONr_mcbond_other
X-RAY DIFFRACTIONr_mcangle_it1.64223968
X-RAY DIFFRACTIONr_scbond_it2.23731877
X-RAY DIFFRACTIONr_scangle_it3.4334.51594
X-RAY DIFFRACTIONr_rigid_bond_restr
X-RAY DIFFRACTIONr_sphericity_free
X-RAY DIFFRACTIONr_sphericity_bonded
LS refinement shellResolution: 2.33→2.391 Å / Total num. of bins used: 20
RfactorNum. reflection% reflection
Rfree0.345 98 -
Rwork0.247 1900 -
obs--84.95 %

+
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