[English] 日本語
Yorodumi
- PDB-4ovv: Crystal Structure of PI3Kalpha in complex with diC4-PIP2 -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 4ovv
TitleCrystal Structure of PI3Kalpha in complex with diC4-PIP2
Components
  • Phosphatidylinositol 3-kinase regulatory subunit alpha
  • Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform
KeywordsTRANSFERASE/TRANSFERASE REGULATOR / p110 / p85 / PI3KCA / PI3K / PIK3R1 / phosphatidilynositol 3 / 4 / 5 triphosphate / PIP2 / phosphatidylinositol 4 / 5 bisphosphate / lipid kinase / phosphoinositide / 3-kinase / signaling / phosphatidylinositol 3-kinase / TRANSFERASE-TRANSFERASE REGULATOR complex
Function / homology
Function and homology information


perinuclear endoplasmic reticulum membrane / response to muscle inactivity / negative regulation of actin filament depolymerization / regulation of toll-like receptor 4 signaling pathway / response to L-leucine / phosphatidylinositol kinase activity / regulation of actin filament organization / phosphatidylinositol 3-kinase regulator activity / response to butyrate / positive regulation of focal adhesion disassembly ...perinuclear endoplasmic reticulum membrane / response to muscle inactivity / negative regulation of actin filament depolymerization / regulation of toll-like receptor 4 signaling pathway / response to L-leucine / phosphatidylinositol kinase activity / regulation of actin filament organization / phosphatidylinositol 3-kinase regulator activity / response to butyrate / positive regulation of focal adhesion disassembly / autosome genomic imprinting / IRS-mediated signalling / cellular response to hydrostatic pressure / phosphatidylinositol 3-kinase activator activity / interleukin-18-mediated signaling pathway / PI3K events in ERBB4 signaling / myeloid leukocyte migration / 1-phosphatidylinositol-3-kinase regulator activity / phosphatidylinositol 3-kinase regulatory subunit binding / neurotrophin TRKA receptor binding / Activated NTRK2 signals through PI3K / positive regulation of protein localization to membrane / Activated NTRK3 signals through PI3K / cis-Golgi network / ErbB-3 class receptor binding / negative regulation of fibroblast apoptotic process / cardiac muscle cell contraction / RHOF GTPase cycle / kinase activator activity / phosphatidylinositol 3-kinase complex, class IB / vasculature development / transmembrane receptor protein tyrosine kinase adaptor activity / RHOD GTPase cycle / Signaling by cytosolic FGFR1 fusion mutants / regulation of cellular respiration / positive regulation of endoplasmic reticulum unfolded protein response / enzyme-substrate adaptor activity / phosphatidylinositol 3-kinase complex, class IA / anoikis / phosphatidylinositol 3-kinase complex / Nephrin family interactions / RND1 GTPase cycle / Costimulation by the CD28 family / relaxation of cardiac muscle / positive regulation of leukocyte migration / 1-phosphatidylinositol-4-phosphate 3-kinase activity / 1-phosphatidylinositol-4,5-bisphosphate 3-kinase activity / MET activates PI3K/AKT signaling / RND2 GTPase cycle / PI3K/AKT activation / positive regulation of filopodium assembly / RND3 GTPase cycle / phosphatidylinositol-4,5-bisphosphate 3-kinase / vascular endothelial growth factor signaling pathway / negative regulation of stress fiber assembly / growth hormone receptor signaling pathway / phosphatidylinositol 3-kinase / insulin binding / phosphatidylinositol-3-phosphate biosynthetic process / RHOV GTPase cycle / 1-phosphatidylinositol-3-kinase activity / negative regulation of cell-matrix adhesion / Signaling by ALK / RHOB GTPase cycle / negative regulation of macroautophagy / GP1b-IX-V activation signalling / PI-3K cascade:FGFR3 / Erythropoietin activates Phosphoinositide-3-kinase (PI3K) / PI-3K cascade:FGFR2 / response to dexamethasone / RHOJ GTPase cycle / PI-3K cascade:FGFR4 / protein kinase activator activity / RHOC GTPase cycle / PI-3K cascade:FGFR1 / negative regulation of osteoclast differentiation / intracellular glucose homeostasis / CD28 dependent PI3K/Akt signaling / Synthesis of PIPs at the plasma membrane / phosphatidylinositol-mediated signaling / phosphatidylinositol phosphate biosynthetic process / CDC42 GTPase cycle / RHOU GTPase cycle / PI3K events in ERBB2 signaling / negative regulation of anoikis / T cell differentiation / RET signaling / intercalated disc / regulation of multicellular organism growth / insulin receptor substrate binding / Interleukin-3, Interleukin-5 and GM-CSF signaling / RHOG GTPase cycle / extrinsic apoptotic signaling pathway via death domain receptors / PI3K Cascade / RHOA GTPase cycle / positive regulation of TOR signaling / endothelial cell migration / RAC2 GTPase cycle / RAC3 GTPase cycle / Role of phospholipids in phagocytosis
Similarity search - Function
Helix Hairpins - #1490 / PI3Kalpha, catalytic domain / Phosphatidylinositol 3-kinase regulatory subunit alpha, SH3 domain / PIK3R1, inter-SH2 domain / PI3K p85 subunit, C-terminal SH2 domain / PI3K regulatory subunit p85-related , inter-SH2 domain / PI3K p85 subunit, N-terminal SH2 domain / Phosphatidylinositol 3-kinase regulatory subunit P85 inter-SH2 domain / Phosphatidylinositol 3-/4-kinase, catalytic domain / Phosphatidylinositol 3-kinase, accessory domain (PIK) ...Helix Hairpins - #1490 / PI3Kalpha, catalytic domain / Phosphatidylinositol 3-kinase regulatory subunit alpha, SH3 domain / PIK3R1, inter-SH2 domain / PI3K p85 subunit, C-terminal SH2 domain / PI3K regulatory subunit p85-related , inter-SH2 domain / PI3K p85 subunit, N-terminal SH2 domain / Phosphatidylinositol 3-kinase regulatory subunit P85 inter-SH2 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 / PI3-kinase family, p85-binding domain / PI3-kinase family, p85-binding domain / Rho GTPase-activating protein domain / RhoGAP domain / Rho GTPase-activating proteins domain profile. / GTPase-activator protein for Rho-like GTPases / 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) / Rho GTPase activation protein / 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 / SH2 domain / Serine Threonine Protein Phosphatase 5, Tetratricopeptide repeat / Src homology 2 (SH2) domain profile. / Src homology 2 domains / SH2 domain / Src homology 3 domains / SH2 domain superfamily / Ubiquitin-like (UB roll) / SH3-like domain superfamily / Src homology 3 (SH3) domain profile. / SH3 domain / Alpha Horseshoe / Helix Hairpins / 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-PBU / PHOSPHATE ION / Phosphatidylinositol 3-kinase regulatory subunit alpha / Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / Resolution: 3.5 Å
AuthorsGabelli, S.B. / Vogelstein, B. / Miller, M. / Amzel, L.M.
Funding support United States, 1items
OrganizationGrant numberCountry
National Institutes of Health/National Cancer Institute (NIH/NCI)R37 CA043460 United States
CitationJournal: Oncotarget / Year: 2014
Title: Structural basis of nSH2 regulation and lipid binding in PI3K alpha.
Authors: Miller, M.S. / Schmidt-Kittler, O. / Bolduc, D.M. / Brower, E.T. / Chaves-Moreira, D. / Allaire, M. / Kinzler, K.W. / Jennings, I.G. / Thompson, P.E. / Cole, P.A. / Amzel, L.M. / Vogelstein, B. / Gabelli, S.B.
History
DepositionJan 14, 2014Deposition site: RCSB / Processing site: RCSB
Revision 1.0Sep 3, 2014Provider: repository / Type: Initial release
Revision 1.1Sep 10, 2014Group: Structure summary
Revision 1.2Aug 24, 2016Group: Other
Revision 1.3Aug 31, 2016Group: Experimental preparation
Revision 1.4Sep 27, 2017Group: Author supporting evidence / Derived calculations / Category: pdbx_audit_support / pdbx_struct_oper_list
Item: _pdbx_audit_support.country / _pdbx_audit_support.funding_organization / _pdbx_struct_oper_list.symmetry_operation
Revision 1.5Dec 4, 2019Group: Author supporting evidence / Category: pdbx_audit_support / Item: _pdbx_audit_support.funding_organization
Revision 1.6Dec 27, 2023Group: Data collection / Database references ...Data collection / Database references / Derived calculations / Structure summary
Category: chem_comp / chem_comp_atom ...chem_comp / chem_comp_atom / chem_comp_bond / database_2 / entity / pdbx_entity_nonpoly
Item: _chem_comp.name / _database_2.pdbx_DOI ..._chem_comp.name / _database_2.pdbx_DOI / _database_2.pdbx_database_accession / _entity.pdbx_description / _pdbx_entity_nonpoly.name

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

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


Theoretical massNumber of molelcules
Total (without water)162,8535
Polymers161,4902
Non-polymers1,3643
Water724
1


  • Idetical with deposited unit
  • defined by author&software
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area7670 Å2
ΔGint-20 kcal/mol
Surface area58870 Å2
MethodPISA
Unit cell
Length a, b, c (Å)114.259, 116.083, 148.743
Angle α, β, γ (deg.)90.000, 90.000, 90.000
Int Tables number19
Space group name H-MP212121

-
Components

#1: Protein Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform / PtdIns-3-kinase subunit alpha / Phosphatidylinositol 4 / 5-bisphosphate 3-kinase 110 kDa catalytic ...PtdIns-3-kinase subunit alpha / Phosphatidylinositol 4 / 5-bisphosphate 3-kinase 110 kDa catalytic subunit alpha / p110alpha / Phosphoinositide-3-kinase catalytic alpha polypeptide / Serine/threonine protein kinase PIK3CA


Mass: 127822.578 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: PIK3CA / Plasmid: pFastbac HT-A / Cell line (production host): sf9 / Production host: Spodoptera frugiperda (fall armyworm)
References: UniProt: P42336, phosphatidylinositol-4,5-bisphosphate 3-kinase
#2: Protein Phosphatidylinositol 3-kinase regulatory subunit alpha / PtdIns-3-kinase regulatory subunit alpha / Phosphatidylinositol 3-kinase 85 kDa regulatory subunit ...PtdIns-3-kinase regulatory subunit alpha / Phosphatidylinositol 3-kinase 85 kDa regulatory subunit alpha / PtdIns-3-kinase regulatory subunit p85-alpha


Mass: 33666.961 Da / Num. of mol.: 1 / Fragment: UNP residues 322-600
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: GRB1,PI3KR1,PIK3R1 / Plasmid: pFastbac HT-A / Cell line (production host): sf9 / Production host: Spodoptera frugiperda (fall armyworm) / References: UniProt: P27986
#3: Chemical ChemComp-PBU / (2R)-3-{[(R)-HYDROXY{[(1R,2R,3S,4R,5R,6S)-2,3,6-TRIHYDROXY-4,5-BIS(PHOSPHONOOXY)CYCLOHEXYL]OXY}PHOSPHORYL]OXY}PROPANE-1 ,2-DIYL DIBUTANOATE / di-butanoyl L-alpha-phosphatidyl-D-myo-inositol 4,5-bisphosphate / di-C4-PIP2


Mass: 634.354 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C17H33O19P3
#4: Chemical ChemComp-PO4 / PHOSPHATE ION


Mass: 94.971 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: PO4
#5: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 4 / 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: 3.05 Å3/Da / Density % sol: 59.73 %
Crystal growTemperature: 298 K / Method: vapor diffusion, hanging drop / pH: 6.8 / Details: NaFormate

-
Data collection

DiffractionMean temperature: 100 K
Diffraction sourceSource: SYNCHROTRON / Site: NSLS / Beamline: X25 / Wavelength: 0.9788 Å
DetectorType: ADSC QUANTUM 315 / Detector: CCD / Date: Apr 30, 2009
RadiationProtocol: SINGLE WAVELENGTH / Scattering type: x-ray
Radiation wavelengthWavelength: 0.9788 Å / Relative weight: 1
ReflectionResolution: 3.36→50 Å / Num. obs: 28636 / % possible obs: 99.9 % / Redundancy: 9 % / Rmerge(I) obs: 0.103 / Χ2: 2.127 / Net I/av σ(I): 35.706 / Net I/σ(I): 10.9 / Num. measured all: 256465
Reflection shell

Diffraction-ID: 1 / Rejects: _

Resolution (Å)Redundancy (%)Rmerge(I) obsNum. unique allΧ2% possible all
3.36-3.429.20.71214001.748100
3.42-3.489.20.64414052.283100
3.48-3.559.10.4914241.68100
3.55-3.629.20.40714161.75100
3.62-3.79.20.33613961.802100
3.7-3.789.20.2814181.843100
3.78-3.889.20.23214181.886100
3.88-3.989.10.19514051.907100
3.98-4.19.10.1714131.941100
4.1-4.239.10.14114282.024100
4.23-4.389.10.12614252.201100
4.38-4.5690.10314132.264100
4.56-4.7790.09614312.407100
4.77-5.028.90.09714242.532100
5.02-5.338.90.09614352.651100
5.33-5.748.80.10114412.588100
5.74-6.328.80.09714522.42100
6.32-7.238.60.07614632.302100
7.23-9.18.50.04514782.18599.9
9.1-5080.03615512.17598.4

-
Processing

Software
NameVersionClassificationNB
REFMAC5.6.0117refinement
PDB_EXTRACT3.14data extraction
DENZOdata reduction
SCALEPACKdata scaling
RefinementResolution: 3.5→91.51 Å / Cor.coef. Fo:Fc: 0.918 / Cor.coef. Fo:Fc free: 0.821 / WRfactor Rfree: 0.3388 / WRfactor Rwork: 0.2367 / FOM work R set: 0.7462 / SU B: 90.419 / SU ML: 0.643 / SU R Cruickshank DPI: 0.5687 / SU Rfree: 0.8008 / Cross valid method: THROUGHOUT / σ(F): 0 / ESU R Free: 0.801 / Stereochemistry target values: MAXIMUM LIKELIHOOD
Details: HYDROGENS HAVE BEEN USED IF PRESENT IN THE INPUT U VALUES : RESIDUAL ONLY
RfactorNum. reflection% reflectionSelection details
Rfree0.3388 1316 5.1 %RANDOM
Rwork0.2367 24266 --
obs0.2418 25582 99.84 %-
Solvent computationIon probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.4 Å / Solvent model: MASK
Displacement parametersBiso max: 166.28 Å2 / Biso mean: 94.047 Å2 / Biso min: 42.7 Å2
Baniso -1Baniso -2Baniso -3
1-3.6 Å20 Å20 Å2
2---1.86 Å20 Å2
3----1.73 Å2
Refinement stepCycle: final / Resolution: 3.5→91.51 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms10584 0 83 4 10671
Biso mean--90 75 -
Refine LS restraints
Refine-IDTypeDev idealDev ideal targetNumber
X-RAY DIFFRACTIONr_bond_refined_d0.0150.0210893
X-RAY DIFFRACTIONr_angle_refined_deg1.8651.96914704
X-RAY DIFFRACTIONr_dihedral_angle_1_deg8.0251270
X-RAY DIFFRACTIONr_dihedral_angle_2_deg39.59624.294545
X-RAY DIFFRACTIONr_dihedral_angle_3_deg23.914152026
X-RAY DIFFRACTIONr_dihedral_angle_4_deg21.0721573
X-RAY DIFFRACTIONr_chiral_restr0.1210.21592
X-RAY DIFFRACTIONr_gen_planes_refined0.0080.0218140
LS refinement shellResolution: 3.5→3.591 Å / Total num. of bins used: 20
RfactorNum. reflection% reflection
Rfree0.363 105 -
Rwork0.272 1585 -
all-1690 -
obs--99.88 %
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)
11.0062-0.0079-0.05210.84860.19551.45920.06420.16940.01070.1111-0.06590.2450.0931-0.03560.00170.11290.03790.09070.04720.0080.113266.43362.35191.95
20.53380.73040.38251.85170.22630.79550.10520.2317-0.1539-0.05070.1480.10110.3180.0088-0.25320.29820.01090.0340.2465-0.09640.301971.91837.68188.411
Refinement TLS group
IDRefine-IDRefine TLS-IDAuth asym-IDAuth seq-ID
1X-RAY DIFFRACTION1A-28 - 1053
2X-RAY DIFFRACTION1A1101
3X-RAY DIFFRACTION1B2001
4X-RAY DIFFRACTION1A1201 - 1204
5X-RAY DIFFRACTION2B327 - 598

+
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