[English] 日本語
Yorodumi
- PDB-3l54: Structure of Pi3K gamma with inhibitor -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 3l54
TitleStructure of Pi3K gamma with inhibitor
ComponentsPhosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit gamma isoform
KeywordsTRANSFERASE / Pi3K / Pi3K gamma / phosphatidylinositol / Pi3 / ATP-binding / Kinase / Nucleotide-binding
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 / phosphatidylinositol-mediated signaling / phosphatidylinositol phosphate biosynthetic process / regulation of cell adhesion mediated by integrin / Synthesis of PIPs at the plasma membrane / 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 / neutrophil chemotaxis / phosphatidylinositol 3-kinase/protein kinase B signal transduction / 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 / immune response / G protein-coupled receptor signaling pathway / phosphorylation / protein serine kinase activity / innate immune response / protein serine/threonine kinase activity / ATP binding / membrane / identical protein binding / plasma membrane / cytosol / cytoplasm
Similarity search - Function
PIK3 catalytic subunit gamma, adaptor-binding domain / PIK3 catalytic subunit gamma adaptor-binding domain / Phosphatidylinositol 3-/4-kinase, catalytic domain / Phosphatidylinositol 3-kinase, accessory domain (PIK) / Phosphatidylinositol 3-kinase Catalytic Subunit; Chain A, domain 4 / Phosphatidylinositol 3-kinase Catalytic Subunit; Chain A, domain 4 / Phosphatidylinositol 3-kinase Catalytic Subunit; Chain A, Domain 5 / C2 domain / Phosphatidylinositol 3-kinase, adaptor-binding domain / Phosphatidylinositol 3-kinase adaptor-binding (PI3K ABD) domain profile. ...PIK3 catalytic subunit gamma, adaptor-binding domain / PIK3 catalytic subunit gamma adaptor-binding domain / Phosphatidylinositol 3-/4-kinase, catalytic domain / Phosphatidylinositol 3-kinase, accessory domain (PIK) / Phosphatidylinositol 3-kinase Catalytic Subunit; Chain A, domain 4 / Phosphatidylinositol 3-kinase Catalytic Subunit; Chain A, domain 4 / Phosphatidylinositol 3-kinase Catalytic Subunit; Chain A, Domain 5 / C2 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 / Phosphatidylinositol 3-kinase Catalytic Subunit; Chain A, domain 1 / C2 domain superfamily / Serine Threonine Protein Phosphatase 5, Tetratricopeptide repeat / Ubiquitin-like (UB roll) / Alpha Horseshoe / Armadillo-type fold / Ubiquitin-like domain superfamily / Roll / Protein kinase-like domain superfamily / Immunoglobulin-like / Sandwich / 2-Layer Sandwich / Orthogonal Bundle / Mainly Beta / Mainly Alpha / Alpha Beta
Similarity search - Domain/homology
Chem-LXX / Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.3 Å
AuthorsElkins, P.A. / Smallwood, A.M.
CitationJournal: ACS Med Chem Lett / Year: 2010
Title: Discovery of GSK2126458, a Highly Potent Inhibitor of PI3K and the Mammalian Target of Rapamycin.
Authors: Knight, S.D. / Adams, N.D. / Burgess, J.L. / Chaudhari, A.M. / Darcy, M.G. / Donatelli, C.A. / Luengo, J.I. / Newlander, K.A. / Parrish, C.A. / Ridgers, L.H. / Sarpong, M.A. / Schmidt, S.J. ...Authors: Knight, S.D. / Adams, N.D. / Burgess, J.L. / Chaudhari, A.M. / Darcy, M.G. / Donatelli, C.A. / Luengo, J.I. / Newlander, K.A. / Parrish, C.A. / Ridgers, L.H. / Sarpong, M.A. / Schmidt, S.J. / Van Aller, G.S. / Carson, J.D. / Diamond, M.A. / Elkins, P.A. / Gardiner, C.M. / Garver, E. / Gilbert, S.A. / Gontarek, R.R. / Jackson, J.R. / Kershner, K.L. / Luo, L. / Raha, K. / Sherk, C.S. / Sung, C.M. / Sutton, D. / Tummino, P.J. / Wegrzyn, R.J. / Auger, K.R. / Dhanak, D.
History
DepositionDec 21, 2009Deposition site: RCSB / Processing site: RCSB
Revision 1.0Jun 30, 2010Provider: repository / Type: Initial release
Revision 1.1Jul 13, 2011Group: Version format compliance
Revision 1.2Sep 24, 2014Group: Database references
Revision 1.3Feb 21, 2024Group: Data collection / Database references / Derived calculations
Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / database_2 / 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: Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit gamma isoform
hetero molecules


Theoretical massNumber of molelcules
Total (without water)111,1353
Polymers110,7151
Non-polymers4192
Water48627
1


  • Idetical with deposited unit
  • defined by author
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Unit cell
Length a, b, c (Å)145.262, 68.406, 106.724
Angle α, β, γ (deg.)90.00, 94.76, 90.00
Int Tables number5
Space group name H-MC121

-
Components

#1: Protein Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit gamma isoform / PI3-kinase p110 subunit gamma / PtdIns-3-kinase subunit p110 / PI3Kgamma / PI3K / p120-PI3K


Mass: 110715.109 Da / Num. of mol.: 1 / Fragment: catalytic subunit
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: PIK3CG / Production host: unidentified baculovirus
References: UniProt: P48736, phosphatidylinositol-4,5-bisphosphate 3-kinase
#2: Chemical ChemComp-SO4 / SULFATE ION / Sulfate


Mass: 96.063 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: SO4
#3: Chemical ChemComp-LXX / 6-(1H-pyrazolo[3,4-b]pyridin-5-yl)-4-pyridin-4-ylquinoline


Mass: 323.351 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C20H13N5
#4: Water ChemComp-HOH / water / Water


Mass: 18.015 Da / Num. of mol.: 27 / 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: 2.39 Å3/Da / Density % sol: 48.46 %
Crystal growTemperature: 277 K / Method: vapor diffusion, sitting drop
Details: Protein at 7.9mg/ml in 20mM Tris, pH 7.2, 50mM ammonium sulfate, 1% ethylene glycol, 1% betaine, 0.02% CHAPS, 5mM DTT with 1mM inhbitor reacted overnight at 4C. 2 microliter protein solution ...Details: Protein at 7.9mg/ml in 20mM Tris, pH 7.2, 50mM ammonium sulfate, 1% ethylene glycol, 1% betaine, 0.02% CHAPS, 5mM DTT with 1mM inhbitor reacted overnight at 4C. 2 microliter protein solution plus 2 microliters well in sitting drops. Well consisted of 20% PEG 3350, 0.1M Tris, pH 8.0, 3% 1,6 hexanediol, 0.2M ammonium sulfate. Crystals grew from dilution seeding from apo seeds. Cryo was 25% ethylene glycol mixed with the well, VAPOR DIFFUSION, SITTING DROP, temperature 277K

-
Data collection

Diffraction sourceSource: SYNCHROTRON / Site: APS / Beamline: 22-BM
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthRelative weight: 1
ReflectionResolution: 2.3→50 Å / Num. all: 46614 / Num. obs: 37850 / % possible obs: 81.2 % / Observed criterion σ(F): 2 / Observed criterion σ(I): 2 / Biso Wilson estimate: 52 Å2 / Rsym value: 0.046 / Net I/σ(I): 19.4
Reflection shellResolution: 2.3→2.38 Å / Mean I/σ(I) obs: 2.3 / Rsym value: 0.437 / % possible all: 78.2

-
Processing

Software
NameVersionClassification
DENZOdata reduction
PHENIXmodel building
PHENIX(phenix.refine: 1.5_2)refinement
HKL-2000data reduction
HKL-2000data scaling
PHENIXphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT / Resolution: 2.3→39.431 Å / SU ML: 0.42 / σ(F): 1.34 / Stereochemistry target values: ML
RfactorNum. reflection% reflectionSelection details
Rfree0.2798 1895 5.02 %random 5%
Rwork0.216 ---
obs0.2192 37786 81.07 %-
all-46614 --
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT BULK SOLVENT MODEL / Bsol: 57.716 Å2 / ksol: 0.353 e/Å3
Refinement stepCycle: LAST / Resolution: 2.3→39.431 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms6779 0 30 27 6836
Refine LS restraints
Refine-IDTypeDev idealNumber
X-RAY DIFFRACTIONf_bond_d0.0046957
X-RAY DIFFRACTIONf_angle_d0.7799417
X-RAY DIFFRACTIONf_dihedral_angle_d14.7522555
X-RAY DIFFRACTIONf_chiral_restr0.0541061
X-RAY DIFFRACTIONf_plane_restr0.0031201
LS refinement shell
Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkRefine-ID% reflection obs (%)
2.3-2.35760.3641120.26852316X-RAY DIFFRACTION74
2.3576-2.42130.38371220.27112532X-RAY DIFFRACTION80
2.4213-2.49260.34711320.26542471X-RAY DIFFRACTION80
2.4926-2.5730.31961560.25382585X-RAY DIFFRACTION82
2.573-2.6650.40031350.25712641X-RAY DIFFRACTION83
2.665-2.77160.2911430.25452642X-RAY DIFFRACTION84
2.7716-2.89770.30851430.23072659X-RAY DIFFRACTION85
2.8977-3.05050.30461500.23682663X-RAY DIFFRACTION85
3.0505-3.24150.34531290.23752674X-RAY DIFFRACTION84
3.2415-3.49160.29031480.21722631X-RAY DIFFRACTION83
3.4916-3.84280.23681440.19852599X-RAY DIFFRACTION82
3.8428-4.39820.21991150.16562585X-RAY DIFFRACTION81
4.3982-5.53880.21461240.16362578X-RAY DIFFRACTION80
5.5388-39.43650.24221420.18782315X-RAY DIFFRACTION71
Refinement TLS params.

Method: refined / Refine-ID: X-RAY DIFFRACTION

IDL11 (°2)L12 (°2)L13 (°2)L22 (°2)L23 (°2)L33 (°2)S11 (Å °)S12 (Å °)S13 (Å °)S21 (Å °)S22 (Å °)S23 (Å °)S31 (Å °)S32 (Å °)S33 (Å °)T11 (Å2)T12 (Å2)T13 (Å2)T22 (Å2)T23 (Å2)T33 (Å2)Origin x (Å)Origin y (Å)Origin z (Å)
13.09260.49861.87471.16740.8961.48730.14231.2117-0.6825-0.27980.1006-0.10870.23130.5573-0.24910.37820.1796-0.14210.4801-0.17060.232237.9001-19.106812.7292
21.3885-1.1477-0.25591.0907-0.1651.8070.28850.0738-0.74050.05780.1350.77750.0914-0.7975-0.0550.09250.03220.27760.47320.19430.542711.7177-10.470837.2309
30.80140.1659-0.26080.53520.16890.5160.08110.28270.0419-0.357-0.0536-0.2901-0.00220.5958-0.03260.36530.13480.08610.6219-0.00590.242964.4508-6.010513.9928
41.4214-0.0397-0.03890.7485-0.45930.2973-0.00040.67080.163-0.1665-0.0492-0.17940.2651-0.03710.05130.33580.18730.07430.545-0.01980.237256.181-7.844112.6625
52.1988-0.46830.8090.27710.16220.83310.1680.0535-0.16320.0085-0.01550.01590.00860.1549-0.12090.17730.0582-0.0260.17320.03180.167346.9278-10.061534.6559
62.485-0.26010.06781.27010.40240.3215-0.02510.7414-0.1459-0.50920.13670.4502-0.1952-0.2744-0.15910.2240.1767-0.07510.48240.11750.165917.39784.485612.1818
70.908-0.026-0.21830.32110.37780.53970.08540.79330.0559-0.13-0.3815-0.20990.39370.3990.17410.50690.284-0.040.55360.08270.327327.49995.140918.6316
80.8067-0.65380.25661.99410.3830.3356-0.05580.1625-0.19260.49450.12980.52010.3214-0.2501-0.03720.50650.16930.10110.2310.10570.211330.69825.584734.912
91.0970.01950.12651.36270.25790.39570.0885-0.03620.420.34260.02780.0751-0.369-0.0651-0.1320.45640.18420.15750.19280.09930.313131.026319.789736.3211
Refinement TLS group
IDRefine-IDRefine TLS-IDSelection details
1X-RAY DIFFRACTION1chain A and resid 144:190
2X-RAY DIFFRACTION2chain A and resid 191:321
3X-RAY DIFFRACTION3chain A and resid 350:488
4X-RAY DIFFRACTION4chain A and resid 495:533
5X-RAY DIFFRACTION5chain A and resid 544:725
6X-RAY DIFFRACTION6chain A and resid 726:836
7X-RAY DIFFRACTION7chain A and resid 867:881
8X-RAY DIFFRACTION8chain A and resid 837:866
9X-RAY DIFFRACTION9chain A and resid 882:1090

+
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