[English] 日本語
Yorodumi
- PDB-2x38: The crystal structure of the murine class IA PI 3-kinase p110delt... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 2x38
TitleThe crystal structure of the murine class IA PI 3-kinase p110delta in complex with IC87114.
ComponentsPHOSPHATIDYLINOSITOL-4,5-BISPHOSPHATE 3-KINASE CATALYTIC SUBUNIT DELTA ISOFORM
KeywordsTRANSFERASE / PHOSPHOINOSITIDE 3-KINASE / ISOFORM-SPECIFIC INHIBITORS / CANCER
Function / homology
Function and homology information


Co-stimulation by ICOS / Erythropoietin activates Phosphoinositide-3-kinase (PI3K) / CD28 dependent PI3K/Akt signaling / Interleukin receptor SHC signaling / Synthesis of PIPs at the plasma membrane / PIP3 activates AKT signaling / Antigen activates B Cell Receptor (BCR) leading to generation of second messengers / Regulation of signaling by CBL / PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling / Interleukin-3, Interleukin-5 and GM-CSF signaling ...Co-stimulation by ICOS / Erythropoietin activates Phosphoinositide-3-kinase (PI3K) / CD28 dependent PI3K/Akt signaling / Interleukin receptor SHC signaling / Synthesis of PIPs at the plasma membrane / PIP3 activates AKT signaling / Antigen activates B Cell Receptor (BCR) leading to generation of second messengers / Regulation of signaling by CBL / PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling / Interleukin-3, Interleukin-5 and GM-CSF signaling / RET signaling / 1-phosphatidylinositol-4,5-bisphosphate 3-kinase activity / phosphatidylinositol-4,5-bisphosphate 3-kinase / phosphatidylinositol 3-kinase / 1-phosphatidylinositol-3-kinase activity / B cell activation / B cell homeostasis / homeostasis of number of cells / defense response to fungus / phosphatidylinositol 3-kinase/protein kinase B signal transduction / positive regulation of angiogenesis / chemotaxis / adaptive immune response / cell differentiation / cell surface receptor signaling pathway / inflammatory response / innate immune response / positive regulation of gene expression / ATP binding / cytosol
Similarity search - Function
PI3Kdelta, catalytic domain / Phosphatidylinositol 3-kinase Catalytic Subunit; Chain A, domain 4 / Phosphatidylinositol 3-kinase Catalytic Subunit; Chain A, domain 4 / Phosphatidylinositol 3-/4-kinase, catalytic domain / Phosphatidylinositol 3-kinase Catalytic Subunit; Chain A, Domain 5 / PI3-kinase family, p85-binding domain / PI3-kinase family, p85-binding domain / Phosphatidylinositol 3-kinase, accessory domain (PIK) / Phosphatidylinositol 3-kinase, adaptor-binding domain / Phosphatidylinositol 3-kinase adaptor-binding (PI3K ABD) domain profile. ...PI3Kdelta, catalytic domain / Phosphatidylinositol 3-kinase Catalytic Subunit; Chain A, domain 4 / Phosphatidylinositol 3-kinase Catalytic Subunit; Chain A, domain 4 / Phosphatidylinositol 3-/4-kinase, catalytic domain / Phosphatidylinositol 3-kinase Catalytic Subunit; Chain A, Domain 5 / PI3-kinase family, p85-binding domain / PI3-kinase family, p85-binding domain / Phosphatidylinositol 3-kinase, accessory domain (PIK) / 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. / C2 phosphatidylinositol 3-kinase-type domain / Phosphoinositide 3-kinase C2 / C2 phosphatidylinositol 3-kinase (PI3K)-type domain profile. / Phosphoinositide 3-kinase, region postulated to contain C2 domain / Phosphoinositide 3-kinase family, accessory domain (PIK domain) / Phosphoinositide 3-kinase family, accessory domain (PIK domain) / Phosphoinositide 3-kinase, accessory (PIK) domain superfamily / C2 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-IC8 / Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform / Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform
Similarity search - Component
Biological speciesMUS MUSCULUS (house mouse)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.2 Å
AuthorsBerndt, A. / Miller, S. / Williams, O. / Lee, D.D. / Houseman, B.T. / Pacold, J.I. / Gorrec, F. / Hon, W.-C. / Liu, Y. / Rommel, C. ...Berndt, A. / Miller, S. / Williams, O. / Lee, D.D. / Houseman, B.T. / Pacold, J.I. / Gorrec, F. / Hon, W.-C. / Liu, Y. / Rommel, C. / Gaillard, P. / Ruckle, T. / Schwarz, M.K. / Shokat, K.M. / Shaw, J.P. / Williams, R.L.
CitationJournal: Nat.Chem.Biol. / Year: 2010
Title: The P110D Structure: Mechanisms for Selectivity and Potency of New Pi(3)K Inhibitors
Authors: Berndt, A. / Miller, S. / Williams, O. / Lee, D.D. / Houseman, B.T. / Pacold, J.I. / Gorrec, F. / Hon, W.-C. / Liu, Y. / Rommel, C. / Gaillard, P. / Ruckle, T. / Schwarz, M.K. / Shokat, K.M. ...Authors: Berndt, A. / Miller, S. / Williams, O. / Lee, D.D. / Houseman, B.T. / Pacold, J.I. / Gorrec, F. / Hon, W.-C. / Liu, Y. / Rommel, C. / Gaillard, P. / Ruckle, T. / Schwarz, M.K. / Shokat, K.M. / Shaw, J.P. / Williams, R.L.
History
DepositionJan 22, 2010Deposition site: PDBE / Processing site: PDBE
SupersessionFeb 2, 2010ID: 2WXE
Revision 1.0Feb 2, 2010Provider: repository / Type: Initial release
Revision 1.1Jul 13, 2011Group: Advisory / Version format compliance
Revision 1.2Apr 24, 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 1.3Dec 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 DELTA ISOFORM
hetero molecules


Theoretical massNumber of molelcules
Total (without water)108,2212
Polymers107,8241
Non-polymers3971
Water72140
1


  • Idetical with deposited unit
  • defined by software
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
MethodPISA
Unit cell
Length a, b, c (Å)142.420, 64.660, 116.900
Angle α, β, γ (deg.)90.00, 103.39, 90.00
Int Tables number5
Space group name H-MC121

-
Components

#1: Protein PHOSPHATIDYLINOSITOL-4,5-BISPHOSPHATE 3-KINASE CATALYTIC SUBUNIT DELTA ISOFORM / PI3-KINASE P110 SUBUNIT DELTA / PTDINS-3-KINASE P110 / P110DELTA / PI3K


Mass: 107823.664 Da / Num. of mol.: 1 / Fragment: RESIDUES 106-1044
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) MUS MUSCULUS (house mouse) / Plasmid: PFASTBAC HTA / Cell line (production host): Sf21 / Production host: SPODOPTERA FRUGIPERDA (fall armyworm)
References: UniProt: Q3UDT3, UniProt: O35904*PLUS, phosphatidylinositol-4,5-bisphosphate 3-kinase
#2: Chemical ChemComp-IC8 / 2-[(6-AMINO-9H-PURIN-9-YL)METHYL]-5-METHYL-3-(2-METHYLPHENYL)QUINAZOLIN-4(3H)-ONE


Mass: 397.433 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C22H19N7O
#3: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 40 / 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: 2.45 Å3/Da / Density % sol: 49.76 % / Description: NONE
Crystal growpH: 6.8
Details: 20% (V/V) GLYCEROL, 10% (V/V) PEG 4K, 30 MM NANO3, 30 MM NA2HPO4, 30 MM (NH4)2SO4, 100 MM IMIDAZOLE PH 6.8

-
Data collection

DiffractionMean temperature: 100 K
Diffraction sourceSource: SYNCHROTRON / Site: Diamond / Beamline: I02 / Wavelength: 0.9791
DetectorType: ADSC CCD / Detector: CCD / Date: Jan 21, 2009
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.9791 Å / Relative weight: 1
ReflectionResolution: 2.2→56.89 Å / Num. obs: 51811 / % possible obs: 98.4 % / Observed criterion σ(I): -3.7 / Redundancy: 3.53 % / Biso Wilson estimate: 37.612 Å2 / Rmerge(I) obs: 0.08 / Net I/σ(I): 13.92
Reflection shellResolution: 2.2→2.22 Å / Redundancy: 3.56 % / Rmerge(I) obs: 0.46 / Mean I/σ(I) obs: 2.62 / % possible all: 97.7

-
Processing

Software
NameVersionClassification
REFMAC5.5.0046refinement
iMOSFLMdata reduction
TRUNCATEdata scaling
PHASERphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: PDB ENTRY 2RD0

2rd0


Resolution: 2.2→56.89 Å / Cor.coef. Fo:Fc: 0.913 / Cor.coef. Fo:Fc free: 0.88 / SU B: 14.695 / SU ML: 0.173 / TLS residual ADP flag: LIKELY RESIDUAL / Cross valid method: THROUGHOUT / ESU R: 0.286 / ESU R Free: 0.227 / Stereochemistry target values: MAXIMUM LIKELIHOOD
Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS. ATOM RECORD CONTAINS RESIDUAL B FACTORS ONLY
RfactorNum. reflection% reflectionSelection details
Rfree0.27719 1578 3 %RANDOM
Rwork0.23852 ---
obs0.2397 50232 98.06 %-
Solvent computationIon probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.2 Å / Solvent model: MASK
Displacement parametersBiso mean: 22.467 Å2
Baniso -1Baniso -2Baniso -3
1-0.26 Å20 Å20.04 Å2
2--0.41 Å20 Å2
3----0.65 Å2
Refinement stepCycle: LAST / Resolution: 2.2→56.89 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms6633 0 30 40 6703
Refine LS restraints
Refine-IDTypeDev idealDev ideal targetNumber
X-RAY DIFFRACTIONr_bond_refined_d0.0110.0226817
X-RAY DIFFRACTIONr_bond_other_d
X-RAY DIFFRACTIONr_angle_refined_deg1.251.9699203
X-RAY DIFFRACTIONr_angle_other_deg
X-RAY DIFFRACTIONr_dihedral_angle_1_deg5.4485813
X-RAY DIFFRACTIONr_dihedral_angle_2_deg35.04723.956316
X-RAY DIFFRACTIONr_dihedral_angle_3_deg16.653151231
X-RAY DIFFRACTIONr_dihedral_angle_4_deg18.91541
X-RAY DIFFRACTIONr_chiral_restr0.0820.21012
X-RAY DIFFRACTIONr_gen_planes_refined0.0050.0215079
X-RAY DIFFRACTIONr_gen_planes_other
X-RAY DIFFRACTIONr_nbd_refined0.2110.23187
X-RAY DIFFRACTIONr_nbd_other
X-RAY DIFFRACTIONr_nbtor_refined0.3040.24696
X-RAY DIFFRACTIONr_nbtor_other
X-RAY DIFFRACTIONr_xyhbond_nbd_refined0.1460.2209
X-RAY DIFFRACTIONr_xyhbond_nbd_other
X-RAY DIFFRACTIONr_metal_ion_refined
X-RAY DIFFRACTIONr_metal_ion_other
X-RAY DIFFRACTIONr_symmetry_vdw_refined0.2170.243
X-RAY DIFFRACTIONr_symmetry_vdw_other
X-RAY DIFFRACTIONr_symmetry_hbond_refined0.2820.26
X-RAY DIFFRACTIONr_symmetry_hbond_other
X-RAY DIFFRACTIONr_symmetry_metal_ion_refined
X-RAY DIFFRACTIONr_symmetry_metal_ion_other
X-RAY DIFFRACTIONr_mcbond_it0.5361.54097
X-RAY DIFFRACTIONr_mcbond_other
X-RAY DIFFRACTIONr_mcangle_it0.99826586
X-RAY DIFFRACTIONr_mcangle_other
X-RAY DIFFRACTIONr_scbond_it1.63432720
X-RAY DIFFRACTIONr_scbond_other
X-RAY DIFFRACTIONr_scangle_it2.5274.52617
X-RAY DIFFRACTIONr_scangle_other
X-RAY DIFFRACTIONr_long_range_B_refined
X-RAY DIFFRACTIONr_long_range_B_other
X-RAY DIFFRACTIONr_rigid_bond_restr
X-RAY DIFFRACTIONr_sphericity_free
X-RAY DIFFRACTIONr_sphericity_bonded
LS refinement shellResolution: 2.2→2.257 Å / Total num. of bins used: 20
RfactorNum. reflection% reflection
Rfree0.314 107 -
Rwork0.259 3715 -
obs--97.7 %
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)
12.37720.08571.26851.02460.10553.8288-0.05050.18020.3386-0.04560.0398-0.0463-0.6501-0.11280.01060.2680.09330.00320.09980.0470.25-14.00833.52920.337
24.35080.32611.50412.5479-0.48284.23430.2865-0.1055-0.32620.2502-0.0639-0.3227-0.13470.8912-0.22260.23610.0293-0.08070.3622-0.03250.35119.17826.39638.14
33.1619-0.2403-1.51661.85180.94995.90530.02910.99080.3258-0.163-0.00360.247-0.2142-2.2071-0.02540.17340.3048-0.02541.38950.13950.2101-48.84324.78415.295
42.57-0.1213-1.06890.72140.0632.55120.0005-0.1880.26950.16120.05870.1663-0.4911-0.6588-0.05910.21350.24460.0140.36650.0230.2011-31.9526.83833.693
50.8413-0.0688-0.46521.3861-0.38893.0914-0.0520.0813-0.10610.0990.0360.04110.3875-0.23610.01610.091-0.0015-0.01880.048-0.02710.0734-11.2762.31730.777
Refinement TLS group
IDRefine-IDRefine TLS-IDAuth asym-IDAuth seq-ID
1X-RAY DIFFRACTION1A109 - 189
2X-RAY DIFFRACTION2A190 - 290
3X-RAY DIFFRACTION3A317 - 494
4X-RAY DIFFRACTION4A511 - 677
5X-RAY DIFFRACTION5A678 - 1027

+
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