[English] 日本語
Yorodumi
- PDB-6pyu: Human PI3Kdelta in complex with Compound 4-2 ((3S)-1'-(cyclopropa... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 6pyu
TitleHuman PI3Kdelta in complex with Compound 4-2 ((3S)-1'-(cyclopropanecarbonyl)-5-(quinoxalin-6-yl)spiro[indole-3,2'-pyrrolidin]-2(1H)-one)
Components
  • Phosphatidylinositol 3-kinase regulatory subunit alpha
  • Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform
KeywordsTRANSFERASE/TRANSFERASE INHIBITOR / PI3Kdelta kinase / transferase / TRANSFERASE-TRANSFERASE INHIBITOR complex
Function / homology
Function and homology information


B cell chemotaxis / mast cell differentiation / mast cell chemotaxis / positive regulation of neutrophil apoptotic process / natural killer cell differentiation / perinuclear endoplasmic reticulum membrane / positive regulation of epithelial tube formation / regulation of toll-like receptor 4 signaling pathway / natural killer cell chemotaxis / neutrophil extravasation ...B cell chemotaxis / mast cell differentiation / mast cell chemotaxis / positive regulation of neutrophil apoptotic process / natural killer cell differentiation / perinuclear endoplasmic reticulum membrane / positive regulation of epithelial tube formation / regulation of toll-like receptor 4 signaling pathway / natural killer cell chemotaxis / neutrophil extravasation / phosphatidylinositol kinase activity / respiratory burst involved in defense response / phosphatidylinositol 3-kinase regulator activity / positive regulation of focal adhesion disassembly / IRS-mediated signalling / phosphatidylinositol 3-kinase activator activity / 1-phosphatidylinositol-3-kinase regulator activity / positive regulation of endoplasmic reticulum unfolded protein response / interleukin-18-mediated signaling pathway / myeloid leukocyte migration / phosphatidylinositol 3-kinase complex / T follicular helper cell differentiation / PI3K events in ERBB4 signaling / phosphatidylinositol 3-kinase regulatory subunit binding / neurotrophin TRKA receptor binding / Activated NTRK2 signals through PI3K / T cell chemotaxis / cis-Golgi network / Activated NTRK3 signals through PI3K / ErbB-3 class receptor binding / transmembrane receptor protein tyrosine kinase adaptor activity / 1-phosphatidylinositol-4-phosphate 3-kinase activity / Signaling by cytosolic FGFR1 fusion mutants / Co-stimulation by ICOS / RHOD GTPase cycle / RHOF GTPase cycle / phosphatidylinositol 3-kinase complex, class IA / kinase activator activity / Nephrin family interactions / natural killer cell activation / Signaling by LTK in cancer / phosphatidylinositol-3-phosphate biosynthetic process / positive regulation of leukocyte migration / Signaling by LTK / MET activates PI3K/AKT signaling / PI3K/AKT activation / 1-phosphatidylinositol-4,5-bisphosphate 3-kinase activity / negative regulation of stress fiber assembly / RND1 GTPase cycle / phosphatidylinositol-4,5-bisphosphate 3-kinase / positive regulation of filopodium assembly / RND2 GTPase cycle / phosphatidylinositol 3-kinase / vascular endothelial growth factor signaling pathway / RND3 GTPase cycle / insulin binding / growth hormone receptor signaling pathway / 1-phosphatidylinositol-3-kinase activity / Signaling by ALK / RHOV GTPase cycle / PI-3K cascade:FGFR3 / RHOB GTPase cycle / mast cell degranulation / natural killer cell mediated cytotoxicity / Erythropoietin activates Phosphoinositide-3-kinase (PI3K) / GP1b-IX-V activation signalling / PI-3K cascade:FGFR2 / phosphatidylinositol-mediated signaling / PI-3K cascade:FGFR4 / PI-3K cascade:FGFR1 / RHOC GTPase cycle / RHOJ GTPase cycle / intracellular glucose homeostasis / phosphatidylinositol phosphate biosynthetic process / negative regulation of osteoclast differentiation / Synthesis of PIPs at the plasma membrane / B cell activation / RHOU GTPase cycle / CDC42 GTPase cycle / RET signaling / PI3K events in ERBB2 signaling / insulin receptor substrate binding / T cell differentiation / Interleukin-3, Interleukin-5 and GM-CSF signaling / extrinsic apoptotic signaling pathway via death domain receptors / PI3K Cascade / RHOG GTPase cycle / negative regulation of cell-matrix adhesion / CD28 dependent PI3K/Akt signaling / RHOA GTPase cycle / RAC2 GTPase cycle / Role of LAT2/NTAL/LAB on calcium mobilization / RAC3 GTPase cycle / Interleukin receptor SHC signaling / GAB1 signalosome / Role of phospholipids in phagocytosis / enzyme-substrate adaptor activity / phosphatidylinositol 3-kinase binding / Signaling by PDGFRA transmembrane, juxtamembrane and kinase domain mutants / Signaling by PDGFRA extracellular domain mutants
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 / Phosphatidylinositol 3-kinase, accessory domain (PIK) ...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 / Phosphatidylinositol 3-kinase, accessory domain (PIK) / 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. / C2 domain / 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 / Serine Threonine Protein Phosphatase 5, Tetratricopeptide repeat / Alpha Horseshoe / Armadillo-type fold / Ubiquitin-like domain superfamily / Protein kinase-like domain superfamily / Immunoglobulin-like / Sandwich / Mainly Beta / Mainly Alpha
Similarity search - Domain/homology
Chem-P5V / Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform / Phosphatidylinositol 3-kinase regulatory subunit alpha
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / FOURIER SYNTHESIS / Resolution: 2.54 Å
AuthorsLesburg, C.A. / Augustin, M.A.
CitationJournal: Bioorg.Med.Chem.Lett. / Year: 2019
Title: Design of selective PI3K delta inhibitors using an iterative scaffold-hopping workflow.
Authors: Fradera, X. / Methot, J.L. / Achab, A. / Christopher, M. / Altman, M.D. / Zhou, H. / McGowan, M.A. / Kattar, S.D. / Wilson, K. / Garcia, Y. / Augustin, M.A. / Lesburg, C.A. / Shah, S. / ...Authors: Fradera, X. / Methot, J.L. / Achab, A. / Christopher, M. / Altman, M.D. / Zhou, H. / McGowan, M.A. / Kattar, S.D. / Wilson, K. / Garcia, Y. / Augustin, M.A. / Lesburg, C.A. / Shah, S. / Goldenblatt, P. / Katz, J.D.
History
DepositionJul 30, 2019Deposition site: RCSB / Processing site: RCSB
Revision 1.0Aug 28, 2019Provider: repository / Type: Initial release
Revision 1.1Sep 4, 2019Group: Data collection / Database references / Category: citation
Item: _citation.journal_volume / _citation.page_first / _citation.page_last
Revision 1.2Mar 13, 2024Group: Advisory / Data collection / Database references
Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / database_2 / pdbx_unobs_or_zero_occ_atoms
Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession

-
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)137,8653
Polymers137,4802
Non-polymers3841
Water21612
1


  • Idetical with deposited unit
  • defined by author&software
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area4320 Å2
ΔGint-14 kcal/mol
Surface area51680 Å2
MethodPISA
Unit cell
Length a, b, c (Å)90.439, 108.587, 142.279
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 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: 116600.633 Da / Num. of mol.: 1 / Fragment: UNP residues 17-1034
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-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: 20879.555 Da / Num. of mol.: 1 / Fragment: UNP residues 131-299
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: PIK3R1, GRB1 / Production host: Spodoptera frugiperda (fall armyworm) / References: UniProt: P27986
#3: Chemical ChemComp-P5V / (3S)-1'-(cyclopropanecarbonyl)-5-(quinoxalin-6-yl)spiro[indole-3,2'-pyrrolidin]-2(1H)-one


Mass: 384.431 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C23H20N4O2
#4: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 12 / 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: 2.63 Å3/Da / Density % sol: 53.19 %
Crystal growTemperature: 293 K / Method: vapor diffusion / Details: not available

-
Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: SLS / Beamline: X06SA / Wavelength: 1 Å
DetectorType: DECTRIS PILATUS 6M / Detector: PIXEL / Date: Feb 13, 2015
RadiationMonochromator: double crystal Si(111) / Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1 Å / Relative weight: 1
ReflectionResolution: 2.54→86.39 Å / Num. obs: 46030 / % possible obs: 98.1 % / Redundancy: 6 % / Biso Wilson estimate: 79.269 Å2 / CC1/2: 0.992 / Rmerge(I) obs: 0.093 / Rrim(I) all: 0.102 / Χ2: 0.941 / Net I/σ(I): 11.78
Reflection shellResolution: 2.54→2.79 Å / Redundancy: 5.9 % / Rmerge(I) obs: 0.987 / Mean I/σ(I) obs: 18.3 / Num. unique obs: 11174 / CC1/2: 0.985 / Rrim(I) all: 0.11 / % possible all: 98.4

-
Processing

Software
NameVersionClassification
REFMAC5.8.0049refinement
XSCALEdata scaling
PDB_EXTRACT3.25data extraction
XDSdata reduction
REFMACphasing
RefinementMethod to determine structure: FOURIER SYNTHESIS / Resolution: 2.54→86.39 Å / Cor.coef. Fo:Fc: 0.936 / Cor.coef. Fo:Fc free: 0.916 / SU B: 31.898 / SU ML: 0.311 / Cross valid method: THROUGHOUT / σ(F): 0 / ESU R: 0.53 / ESU R Free: 0.324
Details: U VALUES : WITH TLS ADDED HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS
RfactorNum. reflection% reflectionSelection details
Rfree0.2916 955 2.1 %RANDOM
Rwork0.2397 ---
obs0.2408 45628 98.95 %-
Solvent computationIon probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.2 Å
Displacement parametersBiso max: 253.08 Å2 / Biso mean: 106.112 Å2 / Biso min: 38.09 Å2
Baniso -1Baniso -2Baniso -3
1-3.9 Å20 Å2-0 Å2
2--3.09 Å2-0 Å2
3----6.99 Å2
Refinement stepCycle: final / Resolution: 2.54→86.39 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms8886 0 29 12 8927
Biso mean--76.13 66.74 -
Num. residues----1090
Refine LS restraints
Refine-IDTypeDev idealDev ideal targetNumber
X-RAY DIFFRACTIONr_bond_refined_d0.0090.0198698
X-RAY DIFFRACTIONr_bond_other_d0.0050.028213
X-RAY DIFFRACTIONr_angle_refined_deg1.2141.96511797
X-RAY DIFFRACTIONr_angle_other_deg0.898318743
X-RAY DIFFRACTIONr_dihedral_angle_1_deg5.73251078
X-RAY DIFFRACTIONr_dihedral_angle_2_deg34.24623.912386
X-RAY DIFFRACTIONr_dihedral_angle_3_deg13.907151448
X-RAY DIFFRACTIONr_dihedral_angle_4_deg15.4441554
X-RAY DIFFRACTIONr_chiral_restr0.0670.21333
X-RAY DIFFRACTIONr_gen_planes_refined0.0050.0219833
X-RAY DIFFRACTIONr_gen_planes_other0.0010.022019
LS refinement shellResolution: 2.54→2.606 Å / Rfactor Rfree error: 0 / Total num. of bins used: 20
RfactorNum. reflection% reflection
Rfree0.491 64 -
Rwork0.413 3289 -
all-3353 -
obs--97.84 %
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)
14.67850.9086-2.753.5708-1.12555.5838-0.1088-0.16460.18450.14330.0974-0.0628-0.05050.00230.01140.038-0.02570.00770.0696-0.01830.18443.4117.148-11.265
21.43280.5249-0.02793.952.34274.27850.0792-0.07670.4793-0.00830.1413-0.0359-0.77220.0497-0.22060.20730.01490.07760.10350.06880.443822.61234.4617.55
31.18470.1963-0.5512.81040.17381.6398-0.19280.1802-0.2757-0.15560.09320.31060.4982-0.29280.09950.2935-0.1188-0.00460.2297-0.07830.38475.85-8.3927.032
43.28610.1474-0.9391.45920.31261.9384-0.10980.1793-0.22940.04580.0540.43890.1965-0.6240.05580.0223-0.0629-0.00650.2290.06540.3259-0.39110.51217.61
52.80780.0542-1.28991.4874-0.19654.06660.0199-0.2301-0.01650.09720.0011-0.4691-0.13280.7853-0.0210.0325-0.0395-0.03410.17020.01810.310835.80116.46623.124
62.85810.4731.02361.29060.13884.07170.102-0.4015-0.08760.5184-0.0948-0.0780.05860.2065-0.00730.2114-0.0226-0.02680.09180.03740.264721.88812.66545.549
71.67911.3926-2.9641.3827-2.8556.5052-0.113-0.0701-0.1427-0.0985-0.1069-0.13780.17760.26680.21990.1738-0.02710.03250.0732-0.0390.307929.214-8.9328.05
Refinement TLS group
IDRefine-IDRefine TLS-IDAuth asym-IDAuth seq-ID
1X-RAY DIFFRACTION1A17 - 108
2X-RAY DIFFRACTION2A109 - 278
3X-RAY DIFFRACTION3A279 - 474
4X-RAY DIFFRACTION4A475 - 675
5X-RAY DIFFRACTION5A676 - 830
6X-RAY DIFFRACTION6A831 - 1034
7X-RAY DIFFRACTION7B432 - 599

+
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