[English] 日本語
Yorodumi
- PDB-7kke: Phosphoinositide 3-Kinase gamma bound to a thiazole inhibitor -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 7kke
TitlePhosphoinositide 3-Kinase gamma bound to a thiazole inhibitor
ComponentsPhosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform
KeywordsTRANSFERASE/Inhibitor / KINASE / INHIBITOR / TRANSFERASE-Inhibitor complex
Function / homology
Function and homology information


secretory granule localization / negative regulation of triglyceride catabolic process / natural killer cell chemotaxis / neutrophil extravasation / phosphatidylinositol-4-phosphate 3-kinase / positive regulation of acute inflammatory response / respiratory burst involved in defense response / negative regulation of cardiac muscle contraction / regulation of calcium ion transmembrane transport / T cell chemotaxis ...secretory granule localization / negative regulation of triglyceride catabolic process / natural killer cell chemotaxis / neutrophil extravasation / phosphatidylinositol-4-phosphate 3-kinase / positive regulation of acute inflammatory response / respiratory burst involved in defense response / negative regulation of cardiac muscle contraction / regulation of calcium ion transmembrane transport / T cell chemotaxis / negative regulation of fibroblast apoptotic process / phosphatidylinositol 3-kinase complex, class IB / sphingosine-1-phosphate receptor signaling pathway / phosphatidylinositol 3-kinase complex, class IA / dendritic cell chemotaxis / 1-phosphatidylinositol-4-phosphate 3-kinase activity / 1-phosphatidylinositol-4,5-bisphosphate 3-kinase activity / phosphatidylinositol-4,5-bisphosphate 3-kinase / phosphatidylinositol 3-kinase / phosphatidylinositol-3-phosphate biosynthetic process / 1-phosphatidylinositol-3-kinase activity / mast cell degranulation / Erythropoietin activates Phosphoinositide-3-kinase (PI3K) / hepatocyte apoptotic process / positive regulation of Rac protein signal transduction / regulation of cell adhesion mediated by integrin / Synthesis of PIPs at the plasma membrane / phosphatidylinositol-mediated signaling / phosphatidylinositol phosphate biosynthetic process / regulation of angiogenesis / T cell proliferation / cellular response to cAMP / GPVI-mediated activation cascade / T cell activation / ephrin receptor binding / positive regulation of endothelial cell migration / phosphatidylinositol 3-kinase/protein kinase B signal transduction / neutrophil chemotaxis / positive regulation of cytokine production / positive regulation of MAP kinase activity / platelet aggregation / endocytosis / G beta:gamma signalling through PI3Kgamma / Signaling by CSF1 (M-CSF) in myeloid cells / kinase activity / positive regulation of cytosolic calcium ion concentration / angiogenesis / adaptive immune response / positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction / non-specific serine/threonine protein kinase / protein kinase activity / inflammatory response / phosphorylation / immune response / G protein-coupled receptor signaling pathway / innate immune response / protein serine kinase activity / protein serine/threonine kinase activity / ATP binding / identical protein binding / membrane / plasma membrane / cytoplasm / cytosol
Similarity search - Function
PIK3 catalytic subunit gamma, adaptor-binding domain / PIK3 catalytic subunit gamma adaptor-binding domain / Phosphatidylinositol 3-kinase, adaptor-binding domain / Phosphatidylinositol 3-kinase adaptor-binding (PI3K ABD) domain profile. / PI3-kinase family, Ras-binding domain / Phosphatidylinositol 3-kinase Ras-binding (PI3K RBD) domain / PI3-kinase family, ras-binding domain / Phosphatidylinositol 3-kinase Ras-binding (PI3K RBD) domain profile. / Phosphoinositide 3-kinase C2 / Phosphoinositide 3-kinase, region postulated to contain C2 domain ...PIK3 catalytic subunit gamma, adaptor-binding domain / PIK3 catalytic subunit gamma adaptor-binding domain / Phosphatidylinositol 3-kinase, adaptor-binding domain / Phosphatidylinositol 3-kinase adaptor-binding (PI3K ABD) domain profile. / PI3-kinase family, Ras-binding domain / Phosphatidylinositol 3-kinase Ras-binding (PI3K RBD) domain / PI3-kinase family, ras-binding domain / Phosphatidylinositol 3-kinase Ras-binding (PI3K RBD) domain profile. / Phosphoinositide 3-kinase C2 / Phosphoinositide 3-kinase, region postulated to contain C2 domain / C2 phosphatidylinositol 3-kinase-type domain / C2 phosphatidylinositol 3-kinase (PI3K)-type domain profile. / Phosphoinositide 3-kinase, accessory (PIK) domain superfamily / Phosphoinositide 3-kinase family, accessory domain (PIK domain) / Phosphoinositide 3-kinase family, accessory domain (PIK domain) / Phosphoinositide 3-kinase, accessory (PIK) domain / Phosphatidylinositol kinase / PIK helical domain profile. / Phosphatidylinositol 3- and 4-kinases signature 1. / Phosphatidylinositol 3/4-kinase, conserved site / Phosphatidylinositol 3- and 4-kinases signature 2. / Phosphatidylinositol 3-/4-kinase, catalytic domain superfamily / Phosphoinositide 3-kinase, catalytic domain / Phosphatidylinositol 3- and 4-kinase / Phosphatidylinositol 3- and 4-kinases catalytic domain profile. / Phosphatidylinositol 3-/4-kinase, catalytic domain / C2 domain superfamily / Armadillo-type fold / Ubiquitin-like domain superfamily / Protein kinase-like domain superfamily
Similarity search - Domain/homology
Chem-WJV / Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / FOURIER SYNTHESIS / Resolution: 2.81 Å
AuthorsJacobs, M.D. / Griffith, J.P.
Funding support United States, 1items
OrganizationGrant numberCountry
Department of Energy (DOE, United States)DE-AC02-05CH11231 United States
CitationJournal: Acs Med.Chem.Lett. / Year: 2021
Title: Discovery of a Novel Series of Potent and Selective Alkynylthiazole-Derived PI3K gamma Inhibitors.
Authors: Bandarage, U.K. / Aronov, A.M. / Cao, J. / Come, J.H. / Cottrell, K.M. / Davies, R.J. / Giroux, S. / Jacobs, M. / Mahajan, S. / Messersmith, D. / Moody, C.S. / Swett, R. / Xu, J.
History
DepositionOct 27, 2020Deposition site: RCSB / Processing site: RCSB
Revision 1.0Mar 24, 2021Provider: repository / Type: Initial release
Revision 1.1Oct 18, 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

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform
hetero molecules


Theoretical massNumber of molelcules
Total (without water)111,6552
Polymers111,2691
Non-polymers3871
Water41423
1


  • Idetical with deposited unit
  • defined by author&software
  • Evidence: gel filtration
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
MethodPISA
Unit cell
Length a, b, c (Å)141.456, 67.050, 107.398
Angle α, β, γ (deg.)90.000, 97.050, 90.000
Int Tables number5
Space group name H-MC121

-
Components

#1: Protein Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform / PtdIns-3-kinase subunit gamma / Phosphatidylinositol 4 / 5-bisphosphate 3-kinase 110 kDa catalytic ...PtdIns-3-kinase subunit gamma / Phosphatidylinositol 4 / 5-bisphosphate 3-kinase 110 kDa catalytic subunit gamma / p110gamma / Phosphoinositide-3-kinase catalytic gamma polypeptide / Serine/threonine protein kinase PIK3CG / p120-PI3K


Mass: 111268.758 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: PIK3CG / Plasmid: pBev12 / Cell line (production host): Sf9 / Production host: Spodoptera frugiperda (fall armyworm)
References: UniProt: P48736, phosphatidylinositol-4,5-bisphosphate 3-kinase, non-specific serine/threonine protein kinase
#2: Chemical ChemComp-WJV / N-[2-(3,3-dimethylbutoxy)ethyl]-N'-{4-methyl-5-[(pyridin-4-yl)ethynyl]-1,3-thiazol-2-yl}urea


Mass: 386.511 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C20H26N4O2S / Feature type: SUBJECT OF INVESTIGATION
#3: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 23 / 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: 2.27 Å3/Da / Density % sol: 45.85 %
Crystal growTemperature: 298 K / Method: vapor diffusion / pH: 8.5
Details: 25% PEG3350, 200MM LITHIUM SULFATE, 10 REMARK 280 MM DTT, 10 MM EDTA, 100 MM TRIS, PH 8.5, VAPOR DIFFUSION, REMARK 280 HANGING DROP, TEMPERATURE 298K

-
Data collection

DiffractionMean temperature: 110 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: ALS / Beamline: 5.0.2 / Wavelength: 1 Å
DetectorType: ADSC QUANTUM 315 / Detector: CCD / Date: Aug 1, 2009
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1 Å / Relative weight: 1
ReflectionResolution: 2.81→62.24 Å / Num. obs: 19864 / % possible obs: 87.3 % / Redundancy: 3.3 % / CC1/2: 0.999 / Rmerge(I) obs: 0.07 / Rpim(I) all: 0.044 / Rrim(I) all: 0.083 / Net I/σ(I): 13.1
Reflection shell

Num. unique obs: 993 / Diffraction-ID: 1

Resolution (Å)Redundancy (%)Rmerge(I) obsNum. measured allCC1/2Rpim(I) allRrim(I) allNet I/σ(I) obs% possible all
2.81-2.993.71.15436880.5470.6921.3481.142.7
8.086-62.2373.30.0232770.9990.0120.02342.490.3

-
Processing

Software
NameVersionClassification
XDSdata reduction
Aimlessdata scaling
BUSTERrefinement
PDB_EXTRACT3.25data extraction
BUSTERphasing
RefinementMethod to determine structure: FOURIER SYNTHESIS
Starting model: 6C1S

6c1s


Resolution: 2.81→62.24 Å / Cor.coef. Fo:Fc: 0.938 / Cor.coef. Fo:Fc free: 0.884 / Cross valid method: THROUGHOUT / σ(F): 0 / SU Rfree Blow DPI: 0.449
RfactorNum. reflection% reflectionSelection details
Rfree0.2637 937 4.72 %RANDOM
Rwork0.1936 ---
obs0.1967 19864 80.8 %-
Displacement parametersBiso max: 158.52 Å2 / Biso mean: 86.79 Å2 / Biso min: 26.37 Å2
Baniso -1Baniso -2Baniso -3
1-1.885 Å20 Å2-6.8064 Å2
2--3.6709 Å20 Å2
3----5.5559 Å2
Refine analyzeLuzzati coordinate error obs: 0.37 Å
Refinement stepCycle: final / Resolution: 2.81→62.24 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms6775 0 27 23 6825
Biso mean--66.68 52.92 -
Num. residues----842
Refine LS restraints
Refine-IDTypeNumberRestraint functionWeightDev ideal
X-RAY DIFFRACTIONt_dihedral_angle_d2444SINUSOIDAL2
X-RAY DIFFRACTIONt_trig_c_planes
X-RAY DIFFRACTIONt_gen_planes1161HARMONIC5
X-RAY DIFFRACTIONt_it6967HARMONIC10
X-RAY DIFFRACTIONt_nbd
X-RAY DIFFRACTIONt_improper_torsion
X-RAY DIFFRACTIONt_pseud_angle
X-RAY DIFFRACTIONt_chiral_improper_torsion911SEMIHARMONIC5
X-RAY DIFFRACTIONt_sum_occupancies
X-RAY DIFFRACTIONt_utility_distance
X-RAY DIFFRACTIONt_utility_angle
X-RAY DIFFRACTIONt_utility_torsion
X-RAY DIFFRACTIONt_ideal_dist_contact5409SEMIHARMONIC4
X-RAY DIFFRACTIONt_bond_d6967HARMONIC20.009
X-RAY DIFFRACTIONt_angle_deg9433HARMONIC21.01
X-RAY DIFFRACTIONt_omega_torsion2.7
X-RAY DIFFRACTIONt_other_torsion21.85
LS refinement shellResolution: 2.81→2.93 Å / Rfactor Rfree error: 0
RfactorNum. reflection% reflection
Rfree0.2941 21 4.86 %
Rwork0.2419 411 -
obs--24.1 %
Refinement TLS params.Method: refined / Origin x: 32.4077 Å / Origin y: -20.6799 Å / Origin z: 27.0153 Å
111213212223313233
T-0.0099 Å2-0.0047 Å2-0.0775 Å2--0.1722 Å2-0.0206 Å2---0.1804 Å2
L3.4169 °2-0.9612 °20.414 °2-0.3901 °2-0.0089 °2--1.5661 °2
S-0.1462 Å °0.0134 Å °-0.2156 Å °0.0715 Å °0.0944 Å °0.0962 Å °-0.2282 Å °-0.0395 Å °0.0518 Å °
Refinement TLS groupSelection details: { A|* }

+
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