[English] 日本語
Yorodumi
- PDB-9gcf: HUMAN PI3KDELTA IN COMPLEX WITH ISOCUMARIN INHIBITOR CHF-6523 -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 9gcf
TitleHUMAN PI3KDELTA IN COMPLEX WITH ISOCUMARIN INHIBITOR CHF-6523
Components
  • Phosphatidylinositol 3-kinase regulatory subunit alpha
  • Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform
KeywordsTRANSFERASE / PI3KDELTA KINASE / PI3KDELTA KINASE INHIBITOR
Function / homology
Function and homology information


B cell chemotaxis / RHOC GTPase cycle / PI3K events in ERBB4 signaling / Interleukin-7 signaling / GAB1 signalosome / PI3K events in ERBB2 signaling / MET activates PI3K/AKT signaling / CDC42 GTPase cycle / RHOD GTPase cycle / RHOJ GTPase cycle ...B cell chemotaxis / RHOC GTPase cycle / PI3K events in ERBB4 signaling / Interleukin-7 signaling / GAB1 signalosome / PI3K events in ERBB2 signaling / MET activates PI3K/AKT signaling / CDC42 GTPase cycle / RHOD GTPase cycle / RHOJ GTPase cycle / RAC3 GTPase cycle / Erythropoietin activates Phosphoinositide-3-kinase (PI3K) / FLT3 Signaling / RND2 GTPase cycle / RND1 GTPase cycle / IRS-mediated signalling / GPVI-mediated activation cascade / Signaling by SCF-KIT / Downstream signal transduction / PI3K/AKT activation / Signaling by ALK / Role of phospholipids in phagocytosis / Tie2 Signaling / Role of LAT2/NTAL/LAB on calcium mobilization / CD28 dependent PI3K/Akt signaling / RAC1 GTPase cycle / RAC2 GTPase cycle / Interleukin receptor SHC signaling / RND3 GTPase cycle / Co-stimulation by ICOS / PI-3K cascade:FGFR1 / PI-3K cascade:FGFR2 / PI-3K cascade:FGFR3 / PI-3K cascade:FGFR4 / Antigen activates B Cell Receptor (BCR) leading to generation of second messengers / PI3K Cascade / PIP3 activates AKT signaling / GP1b-IX-V activation signalling / RAF/MAP kinase cascade / PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling / Synthesis of PIPs at the plasma membrane / RHOA GTPase cycle / RHOF GTPase cycle / DAP12 signaling / RHOU GTPase cycle / RHOV GTPase cycle / mast cell differentiation / mast cell chemotaxis / Regulation of signaling by CBL / positive regulation of neutrophil apoptotic process / Downstream TCR signaling / natural killer cell differentiation / RHOG GTPase cycle / positive regulation of epithelial tube formation / natural killer cell chemotaxis / neutrophil extravasation / RET signaling / Interleukin-3, Interleukin-5 and GM-CSF signaling / VEGFA-VEGFR2 Pathway / respiratory burst involved in defense response / phosphatidylinositol 3-kinase regulator activity / phosphatidylinositol 3-kinase activator activity / 1-phosphatidylinositol-3-kinase regulator activity / positive regulation of endoplasmic reticulum unfolded protein response / phosphatidylinositol 3-kinase complex / T cell chemotaxis / ErbB-3 class receptor binding / transmembrane receptor protein tyrosine kinase adaptor activity / 1-phosphatidylinositol-4-phosphate 3-kinase activity / Co-stimulation by ICOS / phosphatidylinositol 3-kinase complex, class IA / natural killer cell activation / phosphatidylinositol-3-phosphate biosynthetic process / 1-phosphatidylinositol-4,5-bisphosphate 3-kinase activity / phosphatidylinositol-4,5-bisphosphate 3-kinase / phosphatidylinositol 3-kinase / vascular endothelial growth factor signaling pathway / Extra-nuclear estrogen signaling / 1-phosphatidylinositol-3-kinase activity / G alpha (q) signalling events / mast cell degranulation / Erythropoietin activates Phosphoinositide-3-kinase (PI3K) / phosphatidylinositol-mediated signaling / intracellular glucose homeostasis / phosphatidylinositol phosphate biosynthetic process / Synthesis of PIPs at the plasma membrane / B cell activation / RET signaling / insulin receptor substrate binding / T cell differentiation / Interleukin-3, Interleukin-5 and GM-CSF signaling / CD28 dependent PI3K/Akt signaling / Interleukin receptor SHC signaling / enzyme-substrate adaptor activity / phosphatidylinositol 3-kinase binding / insulin-like growth factor receptor binding / positive regulation of endothelial cell proliferation / neutrophil chemotaxis / positive regulation of endothelial cell migration / substrate adhesion-dependent cell spreading
Similarity search - Function
PI3Kdelta, 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 / PI3-kinase family, p85-binding domain / PI3-kinase family, p85-binding domain / Rho GTPase-activating protein domain ...PI3Kdelta, 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 / 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 / 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. / Rho GTPase activation protein / 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 / SH2 domain / Src homology 2 (SH2) domain profile. / Src homology 2 domains / SH2 domain / SH2 domain superfamily / Src homology 3 domains / SH3-like domain superfamily / Src homology 3 (SH3) domain profile. / SH3 domain / Armadillo-type fold / Ubiquitin-like domain superfamily / Protein kinase-like domain superfamily
Similarity search - Domain/homology
: / Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform / Phosphatidylinositol 3-kinase regulatory subunit alpha
Similarity search - Component
Biological speciesHomo sapiens (human)
Bos taurus (domestic cattle)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.89 Å
AuthorsPala, D. / Bruno, P. / Capelli, A.M. / Biagetti, M.
Funding support1items
OrganizationGrant numberCountry
Not funded
CitationJournal: J.Med.Chem. / Year: 2025
Title: Discovery of CHF-6523, an Inhaled Selective PI3K delta Inhibitor for the Treatment of Chronic Obstructive Pulmonary Disease.
Authors: Bruno, P. / Pala, D. / Micoli, A. / Corsi, M. / Accetta, A. / Carzaniga, L. / Ronchi, P. / Fiorelli, C. / Formica, M. / Pizzirani, D. / Mazzucato, R. / Guariento, S. / Bertolini, S. / ...Authors: Bruno, P. / Pala, D. / Micoli, A. / Corsi, M. / Accetta, A. / Carzaniga, L. / Ronchi, P. / Fiorelli, C. / Formica, M. / Pizzirani, D. / Mazzucato, R. / Guariento, S. / Bertolini, S. / Martucci, C. / Allen, A.D. / Mileo, V. / Capacchi, S. / Gallo, P.M. / Fioni, A. / Xanxo Fernandez, S. / Villetti, G. / Puccini, P. / Civelli, M. / Guala, M. / Retini, M. / Martinelli, P. / Visentini, F. / Pavoni, V. / Daldosso, M. / Fontana, S. / Biagetti, M. / Capelli, A.M.
History
DepositionAug 1, 2024Deposition site: PDBE / Processing site: PDBE
Revision 1.0Dec 18, 2024Provider: repository / Type: Initial release
Revision 1.1Feb 26, 2025Group: Database references / Category: citation / citation_author
Item: _citation.journal_volume / _citation.page_first ..._citation.journal_volume / _citation.page_first / _citation.page_last / _citation.year / _citation_author.identifier_ORCID

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

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


Theoretical massNumber of molelcules
Total (without water)141,2153
Polymers140,6272
Non-polymers5891
Water00
1


  • Idetical with deposited unit
  • defined by author&software
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area4320 Å2
ΔGint-15 kcal/mol
Surface area51700 Å2
MethodPISA
Unit cell
Length a, b, c (Å)90.324, 108.450, 142.160
Angle α, β, γ (deg.)90.00, 90.00, 90.00
Int Tables number19
Space group name H-MP212121

-
Components

#1: Protein Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform / PI3-kinase subunit delta / PI3K-delta / PI3Kdelta / PtdIns-3-kinase subunit delta / ...PI3-kinase subunit delta / PI3K-delta / PI3Kdelta / PtdIns-3-kinase subunit delta / Phosphatidylinositol 4 / 5-bisphosphate 3-kinase 110 kDa catalytic subunit delta / PtdIns-3-kinase subunit p110-delta / p110delta


Mass: 119633.023 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: PIK3CD / Production host: Spodoptera frugiperda (fall armyworm)
References: UniProt: O00329, phosphatidylinositol 3-kinase, phosphatidylinositol-4,5-bisphosphate 3-kinase
#2: Protein Phosphatidylinositol 3-kinase regulatory subunit alpha / PI3-kinase regulatory subunit alpha / PI3K regulatory subunit alpha / PtdIns-3-kinase regulatory ...PI3-kinase regulatory subunit alpha / PI3K regulatory subunit alpha / PtdIns-3-kinase regulatory subunit alpha / Phosphatidylinositol 3-kinase 85 kDa regulatory subunit alpha / PI3-kinase subunit p85-alpha / PtdIns-3-kinase regulatory subunit p85-alpha


Mass: 20993.656 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Bos taurus (domestic cattle) / Gene: PIK3R1 / Production host: Spodoptera frugiperda (fall armyworm) / References: UniProt: P23727
#3: Chemical ChemComp-A1IJ5 / 3-[(1S)-1-[4-azanyl-3-(5-oxidanylpyridin-3-yl)pyrazolo[3,4-d]pyrimidin-1-yl]ethyl]-4-[3-[(4-methylpiperazin-1-yl)methyl]phenyl]isochromen-1-one


Mass: 588.659 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C33H32N8O3
Has ligand of interestY
Has protein modificationN

-
Experimental details

-
Experiment

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

-
Sample preparation

CrystalDensity Matthews: 2.48 Å3/Da / Density % sol: 50.32 %
Crystal growTemperature: 293 K / Method: vapor diffusion, hanging drop / Details: 16% PEG6000, 0.10 M KCL, 0.10 M MES

-
Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: SLS / Beamline: X06SA / Wavelength: 1 Å
DetectorType: DECTRIS EIGER X 16M / Detector: PIXEL / Date: Oct 19, 2016
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1 Å / Relative weight: 1
ReflectionResolution: 2.89→86.22 Å / Num. obs: 30965 / % possible obs: 96.9 % / Redundancy: 3.1 % / Rmerge(I) obs: 0.033 / Net I/σ(I): 20.67
Reflection shellResolution: 2.89→3.13 Å / Rmerge(I) obs: 0.449 / Num. unique obs: 6636

-
Processing

Software
NameVersionClassification
XDSdata reduction
XSCALEdata scaling
REFMAC5.8.0049refinement
MOLREPphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT / Resolution: 2.89→86.22 Å / Cor.coef. Fo:Fc: 0.939 / Cor.coef. Fo:Fc free: 0.908 / SU B: 23.863 / SU ML: 0.448 / Cross valid method: THROUGHOUT / ESU R Free: 0.463 / Stereochemistry target values: MAXIMUM LIKELIHOOD / Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS
RfactorNum. reflection% reflectionSelection details
Rfree0.29637 641 2.1 %RANDOM
Rwork0.22869 ---
obs0.23007 30324 96.87 %-
Solvent computationIon probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.2 Å / Solvent model: MASK
Displacement parametersBiso mean: 102.289 Å2
Baniso -1Baniso -2Baniso -3
1-4.15 Å20 Å2-0 Å2
2--3.13 Å2-0 Å2
3----7.27 Å2
Refinement stepCycle: LAST / Resolution: 2.89→86.22 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms8843 0 44 0 8887
Refine LS restraints
Refine-IDTypeDev idealDev ideal targetNumber
X-RAY DIFFRACTIONr_bond_refined_d0.0070.0198733
X-RAY DIFFRACTIONr_bond_other_d0.0010.028267
X-RAY DIFFRACTIONr_angle_refined_deg0.9671.96611835
X-RAY DIFFRACTIONr_angle_other_deg0.837318873
X-RAY DIFFRACTIONr_dihedral_angle_1_deg4.71951075
X-RAY DIFFRACTIONr_dihedral_angle_2_deg32.98123.838396
X-RAY DIFFRACTIONr_dihedral_angle_3_deg11.331151477
X-RAY DIFFRACTIONr_dihedral_angle_4_deg12.0881558
X-RAY DIFFRACTIONr_chiral_restr0.0510.21326
X-RAY DIFFRACTIONr_gen_planes_refined0.0030.029877
X-RAY DIFFRACTIONr_gen_planes_other0.0010.022049
X-RAY DIFFRACTIONr_nbd_refined
X-RAY DIFFRACTIONr_nbd_other
X-RAY DIFFRACTIONr_nbtor_refined
X-RAY DIFFRACTIONr_nbtor_other
X-RAY DIFFRACTIONr_xyhbond_nbd_refined
X-RAY DIFFRACTIONr_xyhbond_nbd_other
X-RAY DIFFRACTIONr_metal_ion_refined
X-RAY DIFFRACTIONr_metal_ion_other
X-RAY DIFFRACTIONr_symmetry_vdw_refined
X-RAY DIFFRACTIONr_symmetry_vdw_other
X-RAY DIFFRACTIONr_symmetry_hbond_refined
X-RAY DIFFRACTIONr_symmetry_hbond_other
X-RAY DIFFRACTIONr_symmetry_metal_ion_refined
X-RAY DIFFRACTIONr_symmetry_metal_ion_other
X-RAY DIFFRACTIONr_mcbond_it9.97614.0994327
X-RAY DIFFRACTIONr_mcbond_other9.97714.0984326
X-RAY DIFFRACTIONr_mcangle_it14.31423.7775393
X-RAY DIFFRACTIONr_mcangle_other14.31323.7785394
X-RAY DIFFRACTIONr_scbond_it10.15914.644406
X-RAY DIFFRACTIONr_scbond_other10.15914.644407
X-RAY DIFFRACTIONr_scangle_it
X-RAY DIFFRACTIONr_scangle_other14.78224.3786443
X-RAY DIFFRACTIONr_long_range_B_refined17.80961.8769506
X-RAY DIFFRACTIONr_long_range_B_other17.80861.8799507
X-RAY DIFFRACTIONr_rigid_bond_restr
X-RAY DIFFRACTIONr_sphericity_free
X-RAY DIFFRACTIONr_sphericity_bonded
LS refinement shellResolution: 2.89→2.965 Å / Total num. of bins used: 20
RfactorNum. reflection% reflection
Rfree0.397 53 -
Rwork0.358 2152 -
obs--95.79 %

+
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