[English] 日本語
Yorodumi
- PDB-7rsp: Structure of the VPS34 kinase domain with compound 14 -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 7rsp
TitleStructure of the VPS34 kinase domain with compound 14
ComponentsPhosphatidylinositol 3-kinase catalytic subunit type 3
KeywordsTRANSFERASE/TRANSFERASE inhibitor / VPS34 inhibitor / endosomal trafficking / authophagy / ONCOPROTEIN / TRANSFERASE-TRANSFERASE inhibitor complex
Function / homology
Function and homology information


Toll Like Receptor 9 (TLR9) Cascade / protein lipidation / Synthesis of PIPs at the late endosome membrane / phosphatidylinositol 3-kinase complex, class III / Synthesis of PIPs at the early endosome membrane / phosphatidylinositol 3-kinase complex, class III, type II / phosphatidylinositol 3-kinase complex, class III, type I / positive regulation by host of viral genome replication / Synthesis of PIPs at the Golgi membrane / phosphatidylinositol kinase activity ...Toll Like Receptor 9 (TLR9) Cascade / protein lipidation / Synthesis of PIPs at the late endosome membrane / phosphatidylinositol 3-kinase complex, class III / Synthesis of PIPs at the early endosome membrane / phosphatidylinositol 3-kinase complex, class III, type II / phosphatidylinositol 3-kinase complex, class III, type I / positive regulation by host of viral genome replication / Synthesis of PIPs at the Golgi membrane / phosphatidylinositol kinase activity / protein localization to phagophore assembly site / protein targeting to lysosome / early endosome to late endosome transport / phosphatidylinositol-mediated signaling / phagophore assembly site / Translation of Replicase and Assembly of the Replication Transcription Complex / autolysosome / phosphatidylinositol 3-kinase / phosphatidylinositol-3-phosphate biosynthetic process / Macroautophagy / 1-phosphatidylinositol-3-kinase activity / axoneme / autophagosome maturation / phosphatidylinositol phosphate biosynthetic process / autophagosome assembly / PI3K Cascade / RHO GTPases Activate NADPH Oxidases / regulation of macroautophagy / cellular response to glucose starvation / regulation of cytokinesis / regulation of autophagy / macroautophagy / Antigen Presentation: Folding, assembly and peptide loading of class I MHC / autophagy / peroxisome / endocytosis / phagocytic vesicle membrane / late endosome / Translation of Replicase and Assembly of the Replication Transcription Complex / kinase activity / midbody / endosome / protein kinase activity / cell cycle / cell division / phosphorylation / SARS-CoV-2 activates/modulates innate and adaptive immune responses / ATP binding / membrane / cytosol / cytoplasm
Similarity search - Function
Phosphatidylinositol 3-kinase, Vps34 type / 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) / Phosphoinositide 3-kinase, accessory (PIK) domain / Phosphatidylinositol kinase ...Phosphatidylinositol 3-kinase, Vps34 type / 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) / 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 / Protein kinase-like domain superfamily
Similarity search - Domain/homology
Chem-7IK / Phosphatidylinositol 3-kinase catalytic subunit type 3
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 1.67 Å
AuthorsHu, D.X. / Patel, S. / Chen, H. / Wang, S. / Staben, S. / Dimitrova, Y.N. / Wallweber, H.A. / Lee, J.Y. / Chan, G.K.Y. / Sneeringer, C.J. ...Hu, D.X. / Patel, S. / Chen, H. / Wang, S. / Staben, S. / Dimitrova, Y.N. / Wallweber, H.A. / Lee, J.Y. / Chan, G.K.Y. / Sneeringer, C.J. / Prangley, M.S. / Moffat, J.G. / Wu, C. / Schutt, L.K. / Salphati, L. / Pang, J. / McNamara, E. / Huang, H. / Chen, Y. / Wang, Y. / Zhao, W. / Lim, J. / Murthy, A. / Siu, M.
Funding support1items
OrganizationGrant numberCountry
Other private
CitationJournal: J.Med.Chem. / Year: 2022
Title: Structure-Based Design of Potent, Selective, and Orally Bioavailable VPS34 Kinase Inhibitors.
Authors: Hu, D.X. / Patel, S. / Chen, H. / Wang, S. / Staben, S.T. / Dimitrova, Y.N. / Wallweber, H.A. / Lee, J.Y. / Chan, G.K.Y. / Sneeringer, C.J. / Prangley, M.S. / Moffat, J.G. / Wu, K.C. / ...Authors: Hu, D.X. / Patel, S. / Chen, H. / Wang, S. / Staben, S.T. / Dimitrova, Y.N. / Wallweber, H.A. / Lee, J.Y. / Chan, G.K.Y. / Sneeringer, C.J. / Prangley, M.S. / Moffat, J.G. / Wu, K.C. / Schutt, L.K. / Salphati, L. / Pang, J. / McNamara, E. / Huang, H. / Chen, Y. / Wang, Y. / Zhao, W. / Lim, J. / Murthy, A. / Siu, M.
History
DepositionAug 11, 2021Deposition site: RCSB / Processing site: RCSB
Revision 1.0Nov 24, 2021Provider: repository / Type: Initial release
Revision 1.1Sep 14, 2022Group: Database references / Category: citation
Item: _citation.journal_volume / _citation.page_first ..._citation.journal_volume / _citation.page_first / _citation.page_last / _citation.year
Revision 1.2Mar 13, 2024Group: Data collection / Source and taxonomy / Category: chem_comp_atom / chem_comp_bond / entity_src_gen
Revision 1.3Apr 3, 2024Group: Refinement description / Category: pdbx_initial_refinement_model

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Phosphatidylinositol 3-kinase catalytic subunit type 3
B: Phosphatidylinositol 3-kinase catalytic subunit type 3
hetero molecules


Theoretical massNumber of molelcules
Total (without water)140,9857
Polymers140,1522
Non-polymers8335
Water12,124673
1
A: Phosphatidylinositol 3-kinase catalytic subunit type 3
hetero molecules


Theoretical massNumber of molelcules
Total (without water)70,4463
Polymers70,0761
Non-polymers3702
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
MethodPISA
2
B: Phosphatidylinositol 3-kinase catalytic subunit type 3
hetero molecules


Theoretical massNumber of molelcules
Total (without water)70,5384
Polymers70,0761
Non-polymers4633
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
MethodPISA
Unit cell
Length a, b, c (Å)64.320, 117.910, 90.400
Angle α, β, γ (deg.)90.000, 109.540, 90.000
Int Tables number4
Space group name H-MP1211

-
Components

#1: Protein Phosphatidylinositol 3-kinase catalytic subunit type 3 / PI3-kinase type 3 / PI3K type 3 / PtdIns-3-kinase type 3 / Phosphatidylinositol 3-kinase p100 ...PI3-kinase type 3 / PI3K type 3 / PtdIns-3-kinase type 3 / Phosphatidylinositol 3-kinase p100 subunit / Phosphoinositide-3-kinase class 3 / hVps34


Mass: 70075.930 Da / Num. of mol.: 2
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: PIK3C3, VPS34 / Production host: Escherichia coli (E. coli) / References: UniProt: Q8NEB9, phosphatidylinositol 3-kinase
#2: Chemical ChemComp-GOL / GLYCEROL / GLYCERIN / PROPANE-1,2,3-TRIOL / Glycerol


Mass: 92.094 Da / Num. of mol.: 3
Source method: isolated from a genetically manipulated source
Formula: C3H8O3
#3: Chemical ChemComp-7IK / (7R,8R)-2-[(3R)-3-methylmorpholin-4-yl]-7-(propan-2-yl)-6,7-dihydropyrazolo[1,5-a]pyrazin-4(5H)-one


Mass: 278.350 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C14H22N4O2 / Feature type: SUBJECT OF INVESTIGATION
#4: Water ChemComp-HOH / water / Water


Mass: 18.015 Da / Num. of mol.: 673 / 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: 2.31 Å3/Da / Density % sol: 46.64 %
Crystal growTemperature: 277.15 K / Method: vapor diffusion, hanging drop
Details: 0.2M Potassium/Sodium tartrate, 0.1M Bis-Tris propane pH7.5, 20% PEG3350 0.7% v/v 1-butanol

-
Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: SSRL / Beamline: BL12-2 / Wavelength: 0.977 Å
DetectorType: DECTRIS PILATUS 6M / Detector: PIXEL / Date: Oct 3, 2019
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.977 Å / Relative weight: 1
ReflectionResolution: 1.67→43.054 Å / Num. obs: 145165 / % possible obs: 98.8 % / Redundancy: 3.419 % / Biso Wilson estimate: 34.479 Å2 / CC1/2: 1 / Rmerge(I) obs: 0.047 / Rrim(I) all: 0.056 / Χ2: 1.019 / Net I/σ(I): 18.06 / Num. measured all: 496296 / Scaling rejects: 79
Reflection shell

Diffraction-ID: 1

Resolution (Å)Redundancy (%)Rmerge(I) obsMean I/σ(I) obsNum. measured obsNum. possibleNum. unique obsCC1/2Rrim(I) all% possible all
1.67-1.713.4891.5161.053704010828106150.4871.78898
1.71-1.763.4291.1321.373554510558103670.5741.3498.2
1.76-1.813.2820.8661.683327110303101370.6611.03598.4
1.81-1.873.460.6812.2533962995798150.7840.80598.6
1.87-1.933.3890.4942.9332425968895680.8590.58798.8
1.93-23.4060.362431489936192460.9120.42998.8
2-2.073.5320.2755.3931600904989480.9470.32498.9
2.07-2.163.490.1947.330070870186160.9750.2399
2.16-2.253.330.1399.3927410830882310.9840.16599.1
2.25-2.363.4010.10712.1826830798078880.9910.12798.8
2.36-2.493.4150.08314.9125674761075190.9940.09998.8
2.49-2.643.4250.06518.7524310715870970.9960.07899.1
2.64-2.823.5430.0524.0123826677267240.9980.05999.3
2.82-3.053.4360.03730.721493631062560.9980.04499.1
3.05-3.343.280.02540.7218735577357120.9990.0398.9
3.34-3.733.3520.01756.72174585259520910.0299
3.73-4.313.4760.01373.91159864627459910.01699.4
4.31-5.283.4860.01286.33136663938392010.01499.5
5.28-7.473.2970.01376.999873057302910.01599.1
7.47-43.0543.3070.009101.2555191699166910.01198.2

-
Processing

Software
NameVersionClassification
PHENIX1.15.2_3472refinement
XSCALEBUILT=20161205data scaling
PDB_EXTRACT3.27data extraction
XDSBUILT=20190315data reduction
PHASER2.8.3phasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: APO

Resolution: 1.67→43.054 Å / SU ML: 0.25 / Cross valid method: THROUGHOUT / σ(F): 1.35 / Phase error: 29.89 / Stereochemistry target values: ML
RfactorNum. reflection% reflection
Rfree0.2246 1890 1.3 %
Rwork0.2078 143205 -
obs0.208 145095 98.84 %
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT BULK SOLVENT MODEL
Displacement parametersBiso max: 109.96 Å2 / Biso mean: 34.0671 Å2 / Biso min: 21.79 Å2
Refinement stepCycle: final / Resolution: 1.67→43.054 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms8531 0 82 696 9309
Biso mean--38.27 41.13 -
Num. residues----1062
LS refinement shell

Refine-ID: X-RAY DIFFRACTION / Rfactor Rfree error: 0

Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection Rwork% reflection obs (%)
1.67-1.71520.441450.41321085998
1.7152-1.76560.36841420.36041092798
1.7656-1.82260.35461380.34151092098
1.8226-1.88780.3211540.30071099799
1.8878-1.96330.2751370.2751097199
1.9633-2.05270.26831510.25761100999
2.0527-2.16090.28151440.23771101699
2.1609-2.29630.25331440.2181103099
2.2963-2.47360.28081480.2151100999
2.4736-2.72250.23081440.2141104499
2.7225-3.11630.22731460.20181109899
3.1163-3.92580.1891500.17091108499
3.9258-43.0540.1531470.15251124199
Refinement TLS params.Method: refined / Origin x: 42.9795 Å / Origin y: 13.3457 Å / Origin z: 92.8537 Å
111213212223313233
T0.2521 Å20.0097 Å20.0267 Å2-0.2659 Å20.0113 Å2--0.3331 Å2
L0.0868 °20.0327 °20.1843 °2-0.0127 °20.066 °2--0.3966 °2
S0.01 Å °0.0024 Å °-0.019 Å °-0.0073 Å °0.0125 Å °0.0058 Å °0.0115 Å °-0.0094 Å °-0 Å °
Refinement TLS group
IDRefine-IDRefine TLS-IDSelection detailsAuth asym-IDAuth seq-ID
1X-RAY DIFFRACTION1allA286 - 1001
2X-RAY DIFFRACTION1allA901
3X-RAY DIFFRACTION1allB282 - 901
4X-RAY DIFFRACTION1allB901
5X-RAY DIFFRACTION1allM1 - 694

+
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