[English] 日本語
Yorodumi
- PDB-7por: PI3 kinase delta in complex with N-[2-(2-fluoro-4-{[4-(propan-2-y... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 7por
TitlePI3 kinase delta in complex with N-[2-(2-fluoro-4-{[4-(propan-2-yl)piperazin-1-yl]methyl}phenyl)pyridin-4-yl]-2-methoxy-5-(morpholin-4-yl)pyridine-3-sulfonamide
ComponentsPhosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform
KeywordsSIGNALING PROTEIN / PI3 KINASE DELTA
Function / homology
Function and homology information


Erythropoietin activates Phosphoinositide-3-kinase (PI3K) / 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 / phosphatidylinositol 3-kinase complex ...Erythropoietin activates Phosphoinositide-3-kinase (PI3K) / 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 / phosphatidylinositol 3-kinase complex / 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 / B cell activation / phosphatidylinositol-mediated signaling / 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 / kinase activity / adaptive immune response / cell differentiation / cell surface receptor signaling pathway / inflammatory response / negative regulation of gene expression / innate immune response / positive regulation of gene expression / ATP binding / plasma membrane / cytosol / cytoplasm
Similarity search - Function
PI3Kdelta, catalytic domain / PI3-kinase family, p85-binding domain / PI3-kinase family, p85-binding 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. / C2 phosphatidylinositol 3-kinase-type domain ...PI3Kdelta, catalytic domain / PI3-kinase family, p85-binding domain / PI3-kinase family, p85-binding 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. / 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 / 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 / C2 domain superfamily / Armadillo-type fold / Ubiquitin-like domain superfamily / Protein kinase-like domain superfamily
Similarity search - Domain/homology
Chem-7XH / Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform
Similarity search - Component
Biological speciesMus musculus (house mouse)
MethodX-RAY DIFFRACTION / SYNCHROTRON / FOURIER SYNTHESIS / Resolution: 2.26 Å
AuthorsRowland, P. / Convery, M.
Funding support1items
OrganizationGrant numberCountry
Not funded
CitationJournal: J.Med.Chem. / Year: 2021
Title: Discovery of GSK251: A Highly Potent, Highly Selective, Orally Bioavailable Inhibitor of PI3K delta with a Novel Binding Mode.
Authors: Down, K. / Amour, A. / Anderson, N.A. / Barton, N. / Campos, S. / Cannons, E.P. / Clissold, C. / Convery, M.A. / Coward, J.J. / Doyle, K. / Duempelfeld, B. / Edwards, C.D. / Goldsmith, M.D. ...Authors: Down, K. / Amour, A. / Anderson, N.A. / Barton, N. / Campos, S. / Cannons, E.P. / Clissold, C. / Convery, M.A. / Coward, J.J. / Doyle, K. / Duempelfeld, B. / Edwards, C.D. / Goldsmith, M.D. / Krause, J. / Mallett, D.N. / McGonagle, G.A. / Patel, V.K. / Rowedder, J. / Rowland, P. / Sharpe, A. / Sriskantharajah, S. / Thomas, D.A. / Thomson, D.W. / Uddin, S. / Hamblin, J.N. / Hessel, E.M.
History
DepositionSep 9, 2021Deposition site: PDBE / Processing site: PDBE
Revision 1.0Sep 29, 2021Provider: repository / Type: Initial release
Revision 1.1Oct 6, 2021Group: Data collection / Database references / Category: citation / citation_author / pdbx_database_proc
Item: _citation.journal_volume / _citation.page_first ..._citation.journal_volume / _citation.page_first / _citation.page_last / _citation_author.identifier_ORCID
Revision 1.2Jun 19, 2024Group: Data collection / Category: chem_comp_atom / chem_comp_bond

-
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)108,4082
Polymers107,8241
Non-polymers5851
Water5,603311
1


  • Idetical with deposited unit
  • defined by author&software
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area0 Å2
ΔGint0 kcal/mol
Surface area38450 Å2
MethodPISA
Unit cell
Length a, b, c (Å)142.000, 64.200, 115.460
Angle α, β, γ (deg.)90.000, 102.270, 90.000
Int Tables number5
Space group name H-MC121

-
Components

#1: Protein Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform / PtdIns-3-kinase subunit delta / Phosphatidylinositol 4 / 5-bisphosphate 3-kinase 110 kDa catalytic ...PtdIns-3-kinase subunit delta / Phosphatidylinositol 4 / 5-bisphosphate 3-kinase 110 kDa catalytic subunit delta / p110delta


Mass: 107823.664 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Mus musculus (house mouse) / Gene: Pik3cd / Production host: Spodoptera frugiperda (fall armyworm)
References: UniProt: O35904, phosphatidylinositol-4,5-bisphosphate 3-kinase
#2: Chemical ChemComp-7XH / ~{N}-[2-[2-fluoranyl-4-[(4-propan-2-ylpiperazin-1-yl)methyl]phenyl]pyridin-4-yl]-2-methoxy-5-morpholin-4-yl-pyridine-3-sulfonamide


Mass: 584.705 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C29H37FN6O4S / Feature type: SUBJECT OF INVESTIGATION
#3: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 311 / Source method: isolated from a natural source / Formula: H2O
Has ligand of interestY

-
Experimental details

-
Experiment

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

-
Sample preparation

CrystalDensity Matthews: 2.38 Å3/Da / Density % sol: 48.42 %
Crystal growTemperature: 293 K / Method: vapor diffusion, sitting drop
Details: Morpheus screen condition G2: 0.1 M buffer system 1 pH 6.5, 0.1 M carboxylic acids, 30% ethylene glycol/PEG 8000

-
Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: ESRF / Beamline: ID30B / Wavelength: 0.965 Å
DetectorType: DECTRIS PILATUS 2M / Detector: PIXEL / Date: Mar 17, 2015
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.965 Å / Relative weight: 1
ReflectionResolution: 2.26→58.27 Å / Num. obs: 47794 / % possible obs: 99.8 % / Redundancy: 3.5 % / CC1/2: 0.999 / Rmerge(I) obs: 0.041 / Net I/σ(I): 14.5
Reflection shellResolution: 2.26→2.34 Å / Redundancy: 3.5 % / Rmerge(I) obs: 0.676 / Mean I/σ(I) obs: 1.6 / Num. unique obs: 4664 / CC1/2: 0.609 / % possible all: 99.9

-
Processing

Software
NameVersionClassification
BUSTER2.11.7 (6-FEB-2020)refinement
XDSdata reduction
Aimlessdata scaling
RefinementMethod to determine structure: FOURIER SYNTHESIS / Resolution: 2.26→58.27 Å / Cor.coef. Fo:Fc: 0.949 / Cor.coef. Fo:Fc free: 0.932 / SU R Cruickshank DPI: 0.264 / Cross valid method: THROUGHOUT / σ(F): 0 / SU R Blow DPI: 0.264 / SU Rfree Blow DPI: 0.193 / SU Rfree Cruickshank DPI: 0.195
RfactorNum. reflection% reflectionSelection details
Rfree0.2219 2363 4.94 %RANDOM
Rwork0.1883 ---
obs0.19 47794 99.8 %-
Displacement parametersBiso max: 159.48 Å2 / Biso mean: 67.32 Å2 / Biso min: 30.38 Å2
Baniso -1Baniso -2Baniso -3
1--0.825 Å20 Å24.6276 Å2
2---0.7732 Å20 Å2
3---1.5982 Å2
Refine analyzeLuzzati coordinate error obs: 0.28 Å
Refinement stepCycle: final / Resolution: 2.26→58.27 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms6920 0 41 311 7272
Biso mean--43.57 63.04 -
Num. residues----859
Refine LS restraints
Refine-IDTypeNumberRestraint functionWeightDev ideal
X-RAY DIFFRACTIONt_dihedral_angle_d2532SINUSOIDAL2
X-RAY DIFFRACTIONt_trig_c_planes
X-RAY DIFFRACTIONt_gen_planes1185HARMONIC5
X-RAY DIFFRACTIONt_it7114HARMONIC10
X-RAY DIFFRACTIONt_nbd
X-RAY DIFFRACTIONt_improper_torsion
X-RAY DIFFRACTIONt_pseud_angle
X-RAY DIFFRACTIONt_chiral_improper_torsion882SEMIHARMONIC5
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_contact5878SEMIHARMONIC4
X-RAY DIFFRACTIONt_bond_d7114HARMONIC20.009
X-RAY DIFFRACTIONt_angle_deg9604HARMONIC20.87
X-RAY DIFFRACTIONt_omega_torsion2.94
X-RAY DIFFRACTIONt_other_torsion17.29
LS refinement shellResolution: 2.26→2.27 Å / Rfactor Rfree error: 0 / Total num. of bins used: 51
RfactorNum. reflection% reflection
Rfree0.243 45 4.71 %
Rwork0.2358 911 -
all0.2361 956 -
obs--99.15 %
Refinement TLS params.Method: refined / Origin x: -19.9728 Å / Origin y: -14.4902 Å / Origin z: 28.6902 Å
111213212223313233
T-0.0078 Å20.1016 Å2-0.0015 Å2--0.0296 Å2-0.0386 Å2---0.0638 Å2
L0.7789 °2-0.2694 °20.2038 °2-0.4161 °20.2786 °2--1.3402 °2
S-0.0356 Å °0.1127 Å °0.0596 Å °-0.001 Å °-0.0976 Å °-0.0197 Å °-0.0184 Å °-0.2851 Å °0.1332 Å °
Refinement TLS groupSelection details: { A|* }

+
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