[English] 日本語
Yorodumi
- PDB-3p2b: Crystal Structure of PI3K gamma with 3-(2-morpholino-6-(pyridin-3... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 3p2b
TitleCrystal Structure of PI3K gamma with 3-(2-morpholino-6-(pyridin-3-ylamino)pyrimidin-4-yl)phenol
ComponentsPhosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit gamma isoform
KeywordsTRANSFERASE/TRANSFERASE INHIBITOR / PI3-kinase p110 subunit gamma / Transferase / Lipid Kinase / ATP Binding / TRANSFERASE-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 / regulation of calcium ion transmembrane transport / positive regulation of acute inflammatory response / respiratory burst involved in defense response / negative regulation of cardiac muscle contraction / T cell chemotaxis ...secretory granule localization / negative regulation of triglyceride catabolic process / natural killer cell chemotaxis / neutrophil extravasation / phosphatidylinositol-4-phosphate 3-kinase / regulation of calcium ion transmembrane transport / positive regulation of acute inflammatory response / respiratory burst involved in defense response / negative regulation of cardiac muscle contraction / T cell chemotaxis / negative regulation of fibroblast apoptotic process / phosphatidylinositol 3-kinase complex, class IB / sphingosine-1-phosphate receptor signaling pathway / 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-kinase complex, class IA / 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 phosphate biosynthetic process / regulation of angiogenesis / T cell proliferation / cellular response to cAMP / GPVI-mediated activation cascade / T cell activation / ephrin receptor binding / neutrophil chemotaxis / positive regulation of endothelial cell migration / 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 / immune response / inflammatory 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-P2B / Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / molecular replacement / Resolution: 3.2 Å
AuthorsKnapp, M.S. / Elling, R.A. / Ornelas, E.
CitationJournal: Bioorg.Med.Chem.Lett. / Year: 2010
Title: Identification and structure-activity relationship of 2-morpholino 6-(3-hydroxyphenyl) pyrimidines, a class of potent and selective PI3 kinase inhibitors.
Authors: Pecchi, S. / Renhowe, P.A. / Taylor, C. / Kaufman, S. / Merritt, H. / Wiesmann, M. / Shoemaker, K.R. / Knapp, M.S. / Ornelas, E. / Hendrickson, T.F. / Fantl, W. / Voliva, C.F.
History
DepositionOct 1, 2010Deposition site: RCSB / Processing site: RCSB
Revision 1.0Aug 17, 2011Provider: repository / Type: Initial release
Revision 1.1Feb 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)111,1062
Polymers110,7561
Non-polymers3491
Water30617
1


  • Idetical with deposited unit
  • defined by author&software
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
MethodPISA
Unit cell
Length a, b, c (Å)141.120, 66.780, 105.970
Angle α, β, γ (deg.)90.000, 96.950, 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 / PI3-kinase subunit gamma / PI3K-gamma / Phosphatidylinositol-4 / 5- ...PtdIns-3-kinase subunit gamma / PI3-kinase subunit gamma / PI3K-gamma / Phosphatidylinositol-4 / 5-bisphosphate 3-kinase 110 kDa catalytic subunit gamma / PtdIns-3-kinase subunit p110-gamma / p120-PI3K


Mass: 110756.164 Da / Num. of mol.: 1 / Fragment: UNP residues 144-1102 / Mutation: Q459R
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: PIK3CG, PK3CG / Plasmid: pVL1393 / Production host: Spodoptera frugiperda (fall armyworm) / Strain (production host): Tn5
References: UniProt: P48736, phosphatidylinositol-4,5-bisphosphate 3-kinase
#2: Chemical ChemComp-P2B / 3-[2-morpholin-4-yl-6-(pyridin-3-ylamino)pyrimidin-4-yl]phenol


Mass: 349.386 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C19H19N5O2
#3: Water ChemComp-HOH / water / Water


Mass: 18.015 Da / Num. of mol.: 17 / 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: 2.24 Å3/Da / Density % sol: 45.03 %
Crystal growTemperature: 291 K / Method: vapor diffusion, hanging drop / pH: 8.5
Details: 16-19% PEG 4000, 0.2M Sodium Acetate, 0.1M Sodium Citrate, 0.1M TRIS pH 8.5 [Protein] ~6mg/mL in 20mM Tris pH 7.2, 50mM AmmSO4, 1% Betaine, 1% Ethylene Glycol, 0.02% CHAPS, 5mM DTT Drop: 1uL ...Details: 16-19% PEG 4000, 0.2M Sodium Acetate, 0.1M Sodium Citrate, 0.1M TRIS pH 8.5 [Protein] ~6mg/mL in 20mM Tris pH 7.2, 50mM AmmSO4, 1% Betaine, 1% Ethylene Glycol, 0.02% CHAPS, 5mM DTT Drop: 1uL + 1uL, VAPOR DIFFUSION, HANGING DROP, temperature 291K

-
Data collection

DiffractionMean temperature: 100 K
Diffraction sourceSource: SYNCHROTRON / Site: ALS / Beamline: 5.0.2 / Wavelength: 1 Å
DetectorType: ADSC QUANTUM 315 / Detector: CCD / Date: Nov 25, 2009
RadiationMonochromator: double-crystal, Si(111) liquid N2 cooled / Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1 Å / Relative weight: 1
ReflectionResolution: 3.05→105.191 Å / Num. all: 18727 / Num. obs: 17914 / % possible obs: 99.2 % / Observed criterion σ(F): 1 / Observed criterion σ(I): 1 / Redundancy: 3.2 % / Rsym value: 0.081 / Net I/σ(I): 10.2
Reflection shell

Diffraction-ID: 1

Resolution (Å)Redundancy (%)Rmerge(I) obsMean I/σ(I) obsNum. measured allNum. unique allRsym value% possible all
3.05-3.213.20.5241.5881727350.52499.9
3.21-3.413.20.3232.4833025670.32399.7
3.41-3.653.20.1854.1782324240.18599.6
3.65-3.943.20.1166.4730822770.11699.8
3.94-4.313.20.07410662520720.07499.4
4.31-4.823.20.05811.9602818900.05899.3
4.82-5.573.20.0679.5532516810.06799.1
5.57-6.8230.0768.3419213760.07697.9
6.82-9.643.10.03514.4338410880.03597
9.64-70.0423.20.03118.319616170.03197.9

-
Phasing

PhasingMethod: molecular replacement
Phasing MRRfactor: 34.91 / Model details: Phaser MODE: MR_AUTO
Highest resolutionLowest resolution
Rotation3.05 Å70.04 Å
Translation3.05 Å70.04 Å

-
Processing

Software
NameVersionClassificationNB
MOSFLMdata reduction
SCALA3.3.15data scaling
PHASER2.1.4phasing
PHENIX1.6.1_357refinement
PDB_EXTRACT3.1data extraction
BOSdata collection
RefinementMethod to determine structure: MOLECULAR REPLACEMENT / Resolution: 3.2→70.04 Å / Occupancy max: 1 / Occupancy min: 0.43 / SU ML: 0.43 / σ(F): 1.35 / Stereochemistry target values: ML
RfactorNum. reflection% reflectionSelection details
Rfree0.263 834 5.14 %RANDOM
Rwork0.1823 ---
obs0.1866 16226 98.9 %-
all-16226 --
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT BULK SOLVENT MODEL / Bsol: 61.479 Å2 / ksol: 0.323 e/Å3
Displacement parametersBiso max: 470.34 Å2 / Biso mean: 81.712 Å2 / Biso min: 12.03 Å2
Baniso -1Baniso -2Baniso -3
1-0.9927 Å20 Å23.7736 Å2
2---6.7497 Å20 Å2
3---5.757 Å2
Refinement stepCycle: LAST / Resolution: 3.2→70.04 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms6383 0 26 17 6426
Refine LS restraints
Refine-IDTypeDev idealNumber
X-RAY DIFFRACTIONf_bond_d0.0026552
X-RAY DIFFRACTIONf_angle_d0.4918890
X-RAY DIFFRACTIONf_chiral_restr0.0351023
X-RAY DIFFRACTIONf_plane_restr0.0021126
X-RAY DIFFRACTIONf_dihedral_angle_d10.3622368
LS refinement shellResolution: 3.2→3.4004 Å / Total num. of bins used: 6
RfactorNum. reflection% reflection
Rfree0.3051 128 -
Rwork0.2158 2576 -
all-2704 -
obs-2731 100 %
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)
12.8011-0.8646-0.58320.49810.4231.61140.01220.326-0.515-0.0356-0.07540.18040.0421-0.030.07360.10030.13170.02650.0825-0.08780.112536.3764-11.938320.5005
22.43691.74751.47971.25331.06110.8984-0.4327-2.6358-0.17360.3150.47520.15230.18461.12320.03010.37980.12140.41722.998-0.38030.651560.0207-11.444957.9862
33.7789-1.43310.01660.56820.14272.34-0.0101-0.6979-0.2507-0.00460.05770.07870.10970.432-0.02290.130.0049-0.02070.29340.12080.14243.3723-11.693333.2544
42.8728-0.0801-0.99530.93630.07960.95550.24791.6841-0.46240.382-0.29490.0858-0.5696-0.97520.06410.29290.3277-0.07550.9394-0.06190.167217.5894-0.77997.006
54.5123-2.47990.25363.4760.31862.25410.4062-0.05280.41830.2885-0.53960.4146-0.6506-0.48360.11160.06350.2325-0.0050.17010.06420.097618.392310.718327.1877
63.3131-1.49360.09722.48841.03623.38270.2474-0.60821.12460.2474-0.1966-0.6633-0.68740.0711-0.06710.4409-0.0329-0.01890.2446-0.09370.450731.141815.081938.9431
Refinement TLS group
IDRefine-IDRefine TLS-IDSelection detailsAuth asym-IDAuth seq-ID
1X-RAY DIFFRACTION1(chain A and resid 143:522)A143 - 522
2X-RAY DIFFRACTION2(chain A and resid 525:548)A525 - 548
3X-RAY DIFFRACTION3(chain A and resid 549:721)A549 - 721
4X-RAY DIFFRACTION4(chain A and resid 722:783)A722 - 783
5X-RAY DIFFRACTION5(chain A and resid 784:952)A784 - 952
6X-RAY DIFFRACTION6(chain A and resid 953:1087)A953 - 1087

+
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