[English] 日本語
Yorodumi
- PDB-2y3a: Crystal structure of p110beta in complex with icSH2 of p85beta an... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 2y3a
TitleCrystal structure of p110beta in complex with icSH2 of p85beta and the drug GDC-0941
Components
  • PHOSPHATIDYLINOSITOL 3-KINASE REGULATORY SUBUNIT BETA
  • PHOSPHATIDYLINOSITOL-4,5-BISPHOSPHATE 3-KINASE CATALYTIC SUBUNIT BETA ISOFORM
KeywordsTRANSFERASE / PHOSPHOINOSITIDE 3-KINASE / RTK
Function / homology
Function and homology information


: / IRS-mediated signalling / Signaling by ALK / negative regulation of hypoxia-induced intrinsic apoptotic signaling pathway / : / Costimulation by the CD28 family / Tie2 Signaling / CD28 dependent PI3K/Akt signaling / PI3K/AKT activation / : ...: / IRS-mediated signalling / Signaling by ALK / negative regulation of hypoxia-induced intrinsic apoptotic signaling pathway / : / Costimulation by the CD28 family / Tie2 Signaling / CD28 dependent PI3K/Akt signaling / PI3K/AKT activation / : / PI3K Cascade / Role of LAT2/NTAL/LAB on calcium mobilization / Downstream signal transduction / GPVI-mediated activation cascade / Interleukin-7 signaling / negative regulation of sprouting angiogenesis / Signaling by SCF-KIT / Role of phospholipids in phagocytosis / negative regulation of vascular endothelial growth factor signaling pathway / G alpha (q) signalling events / Erythropoietin activates Phosphoinositide-3-kinase (PI3K) / Extra-nuclear estrogen signaling / RAF/MAP kinase cascade / Interleukin receptor SHC signaling / Synthesis of PIPs at the plasma membrane / PIP3 activates AKT signaling / Downstream TCR signaling / Regulation of signaling by CBL / regulation of cell-matrix adhesion / positive regulation of neutrophil apoptotic process / PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling / Interleukin-3, Interleukin-5 and GM-CSF signaling / RET signaling / regulation of actin filament polymerization / embryonic cleavage / 1-phosphatidylinositol-3-kinase regulator activity / phosphatidylinositol 3-kinase regulatory subunit binding / negative regulation of cell migration involved in sprouting angiogenesis / angiogenesis involved in wound healing / VEGFA-VEGFR2 Pathway / regulation of stress fiber assembly / sphingosine-1-phosphate receptor signaling pathway / phosphatidylinositol 3-kinase complex, class IA / phosphatidylinositol 3-kinase complex / endothelial cell proliferation / 1-phosphatidylinositol-4-phosphate 3-kinase activity / 1-phosphatidylinositol-4,5-bisphosphate 3-kinase activity / DAP12 signaling / phosphatidylinositol-4,5-bisphosphate 3-kinase / phosphatidylinositol-3-phosphate biosynthetic process / negative regulation of MAPK cascade / 1-phosphatidylinositol-3-kinase activity / positive regulation of Rac protein signal transduction / intracellular glucose homeostasis / homophilic cell adhesion via plasma membrane adhesion molecules / phosphatidylinositol-mediated signaling / phosphatidylinositol phosphate biosynthetic process / transcription factor binding / positive regulation of cell adhesion / insulin receptor substrate binding / regulation of protein localization to plasma membrane / negative regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction / phosphotyrosine residue binding / positive regulation of endothelial cell migration / response to endoplasmic reticulum stress / phosphatidylinositol 3-kinase/protein kinase B signal transduction / regulation of autophagy / response to ischemia / brush border membrane / receptor tyrosine kinase binding / platelet activation / autophagy / positive regulation of protein import into nucleus / intracellular calcium ion homeostasis / endocytosis / cellular response to insulin stimulus / positive regulation of nitric oxide biosynthetic process / protein transport / cell migration / insulin receptor signaling pathway / kinase activity / midbody / protein phosphatase binding / non-specific serine/threonine protein kinase / protein heterodimerization activity / phosphorylation / protein serine kinase activity / focal adhesion / positive regulation of gene expression / nucleolus / positive regulation of transcription by RNA polymerase II / nucleoplasm / ATP binding / nucleus / plasma membrane / cytoplasm / cytosol
Similarity search - Function
PI3Kbeta, catalytic domain / Phosphatidylinositol 3-kinase regulatory subunit beta, SH3 domain / Ubiquitin-like (UB roll) - #770 / Helix Hairpins - #1490 / 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) ...PI3Kbeta, catalytic domain / Phosphatidylinositol 3-kinase regulatory subunit beta, SH3 domain / Ubiquitin-like (UB roll) - #770 / Helix Hairpins - #1490 / 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. / SH2 domain / SHC Adaptor Protein / 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 / 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-GD9 / Phosphatidylinositol 3-kinase regulatory subunit beta / Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform
Similarity search - Component
Biological speciesMUS MUSCULUS (house mouse)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 3.3 Å
AuthorsZhang, X. / Vadas, O. / Perisic, O. / Williams, R.L.
CitationJournal: Mol.Cell / Year: 2011
Title: Structure of Lipid Kinase P110Beta-P85Beta Elucidates an Unusual Sh2-Domain-Mediated Inhibitory Mechanism.
Authors: Zhang, X. / Vadas, O. / Perisic, O. / Anderson, K.E. / Clark, J. / Hawkins, P.T. / Stephens, L.R. / Williams, R.L.
History
DepositionDec 20, 2010Deposition site: PDBE / Processing site: PDBE
Revision 1.0Mar 16, 2011Provider: repository / Type: Initial release
Revision 1.1May 8, 2011Group: Version format compliance
Revision 1.2Jul 13, 2011Group: Version format compliance
Revision 1.3Apr 3, 2019Group: Data collection / Other / Source and taxonomy
Category: entity_src_gen / pdbx_database_proc / pdbx_database_status
Item: _entity_src_gen.pdbx_host_org_cell_line / _pdbx_database_status.recvd_author_approval
Revision 1.4Dec 20, 2023Group: Data collection / Database references ...Data collection / Database references / Derived calculations / Other / Refinement description
Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / database_2 / pdbx_database_status / pdbx_initial_refinement_model / struct_site
Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession ..._database_2.pdbx_DOI / _database_2.pdbx_database_accession / _pdbx_database_status.status_code_sf / _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 BETA ISOFORM
B: PHOSPHATIDYLINOSITOL 3-KINASE REGULATORY SUBUNIT BETA
hetero molecules


Theoretical massNumber of molelcules
Total (without water)161,1023
Polymers160,5892
Non-polymers5141
Water00
1


  • Idetical with deposited unit
  • defined by software
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area5840 Å2
ΔGint-25.6 kcal/mol
Surface area58210 Å2
MethodPISA
Unit cell
Length a, b, c (Å)134.314, 134.314, 428.062
Angle α, β, γ (deg.)90.00, 90.00, 120.00
Int Tables number179
Space group name H-MP6522

-
Components

#1: Protein PHOSPHATIDYLINOSITOL-4,5-BISPHOSPHATE 3-KINASE CATALYTIC SUBUNIT BETA ISOFORM / PI3-KINASE SUBUNIT BETA / PI3K-BETA / PTDINS-3-KINASE SUBUNIT BETA / PHOSPHATIDYLINOSITOL-4 / 5- ...PI3-KINASE SUBUNIT BETA / PI3K-BETA / PTDINS-3-KINASE SUBUNIT BETA / PHOSPHATIDYLINOSITOL-4 / 5-BISPHOSPHATE 3-KINASE 110 KDA CATALYTIC SUBUNIT BETA / PTDINS-3-KINASE SUBUNIT P110-BETA / PIK3CA


Mass: 125242.070 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) MUS MUSCULUS (house mouse) / Plasmid: PFASTBAC-HTB / Cell line (production host): Sf9 / Production host: SPODOPTERA FRUGIPERDA (fall armyworm) / References: UniProt: Q8BTI9, nicotinate riboside kinase
#2: Protein PHOSPHATIDYLINOSITOL 3-KINASE REGULATORY SUBUNIT BETA / PI3-KINASE REGULATORY SUBUNIT BETA / PI3K REGULATORY SUBUNIT BETA / PTDINS-3-KINASE REGULATORY ...PI3-KINASE REGULATORY SUBUNIT BETA / PI3K REGULATORY SUBUNIT BETA / PTDINS-3-KINASE REGULATORY SUBUNIT BETA / PHOSPHATIDYLINOSITOL 3-KINASE 85 KDA REGULATORY SUBUNIT BETA / PI3-KINASE SUBUNIT P85-BETA / PTDINS-3-KINASE REGULATORY SUBUNIT P85-BETA / PIK3R2


Mass: 35346.574 Da / Num. of mol.: 1 / Fragment: ICSH2 DOMAIN, RESIDUES 423-722
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) MUS MUSCULUS (house mouse) / Plasmid: PFASTBAC-1 / Cell line (production host): Sf9 / Production host: SPODOPTERA FRUGIPERDA (fall armyworm) / References: UniProt: O08908
#3: Chemical ChemComp-GD9 / 2-(1H-indazol-4-yl)-6-{[4-(methylsulfonyl)piperazin-1-yl]methyl}-4-morpholin-4-yl-thieno[3,2-d]pyrimidine


Mass: 513.636 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C23H27N7O3S2
Sequence detailsN-TERMINAL 6XHIS TAG

-
Experimental details

-
Experiment

ExperimentMethod: X-RAY DIFFRACTION / Number of used crystals: 1

-
Sample preparation

CrystalDensity Matthews: 3.48 Å3/Da / Density % sol: 64.71 % / Description: NONE
Crystal growpH: 6
Details: PROTEIN WAS CRYSTALLIZED FROM 12% PEG 3350, 0.1 M POTASSIUM CITRATE PH 6, 0.4 M LITHIUM SULFATE

-
Data collection

DiffractionMean temperature: 100 K
Diffraction sourceSource: SYNCHROTRON / Site: ESRF / Beamline: ID14-4 / Wavelength: 0.9765
DetectorType: ADSC QUANTUM 315r / Detector: CCD / Date: Dec 5, 2009
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.9765 Å / Relative weight: 1
ReflectionResolution: 3.3→44 Å / Num. obs: 34250 / % possible obs: 98.9 % / Observed criterion σ(I): 1 / Redundancy: 5.2 % / Biso Wilson estimate: 90.8 Å2 / Rmerge(I) obs: 0.1 / Net I/σ(I): 10.4
Reflection shellResolution: 3.3→3.5 Å / Redundancy: 5.4 % / Rmerge(I) obs: 0.67 / Mean I/σ(I) obs: 1.9 / % possible all: 99.9

-
Processing

Software
NameVersionClassification
BUSTER2.8.0refinement
MOSFLMdata reduction
SCALAdata scaling
PHASERphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: PDB ENTRY 2WHG

2whg


Resolution: 3.3→44.68 Å / Cor.coef. Fo:Fc: 0.8743 / Cor.coef. Fo:Fc free: 0.8398 / Cross valid method: THROUGHOUT / σ(F): 0
Details: RESIDUES 1-12, 228-234, 299-3 -1064 ARE DISORDERED.
RfactorNum. reflection% reflectionSelection details
Rfree0.296 1764 5.15 %RANDOM
Rwork0.234 ---
obs0.2372 34250 --
Displacement parametersBiso mean: 127.72 Å2
Baniso -1Baniso -2Baniso -3
1--27.9399 Å20 Å20 Å2
2---27.9399 Å20 Å2
3---55.8799 Å2
Refine analyzeLuzzati coordinate error obs: 0.906 Å
Refinement stepCycle: LAST / Resolution: 3.3→44.68 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms9813 0 35 0 9848
Refine LS restraints
Refine-IDTypeDev idealNumberRestraint functionWeight
X-RAY DIFFRACTIONt_bond_d0.0110052HARMONIC2
X-RAY DIFFRACTIONt_angle_deg1.3513582HARMONIC2
X-RAY DIFFRACTIONt_dihedral_angle_d3595SINUSOIDAL2
X-RAY DIFFRACTIONt_incorr_chiral_ct
X-RAY DIFFRACTIONt_pseud_angle
X-RAY DIFFRACTIONt_trig_c_planes284HARMONIC2
X-RAY DIFFRACTIONt_gen_planes1428HARMONIC5
X-RAY DIFFRACTIONt_it10052HARMONIC20
X-RAY DIFFRACTIONt_nbd
X-RAY DIFFRACTIONt_omega_torsion2.62
X-RAY DIFFRACTIONt_other_torsion25.33
X-RAY DIFFRACTIONt_improper_torsion
X-RAY DIFFRACTIONt_chiral_improper_torsion1276SEMIHARMONIC5
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_contact12152SEMIHARMONIC4
LS refinement shellResolution: 3.3→3.4 Å / Total num. of bins used: 17
RfactorNum. reflection% reflection
Rfree0.3027 137 5.17 %
Rwork0.263 2514 -
all0.265 2651 -

+
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