[English] 日本語
Yorodumi
- PDB-8c8c: Crystal Structure of Phosphatidylinositol 5-phosphate 4-kinase ty... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 8c8c
TitleCrystal Structure of Phosphatidylinositol 5-phosphate 4-kinase type-2 alpha (PI5P4Ka) bound to an inhibitor
ComponentsPhosphatidylinositol 5-phosphate 4-kinase type-2 alpha
KeywordsTRANSFERASE / Inhibitor / ATP
Function / homology
Function and homology information


vesicle-mediated cholesterol transport / 1-phosphatidylinositol-5-phosphate 4-kinase / 1-phosphatidylinositol-5-phosphate 4-kinase activity / 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate biosynthetic process / Synthesis of PIPs in the nucleus / 1-phosphatidylinositol-4-phosphate 5-kinase activity / autophagosome-lysosome fusion / positive regulation of autophagosome assembly / megakaryocyte development / PI5P Regulates TP53 Acetylation ...vesicle-mediated cholesterol transport / 1-phosphatidylinositol-5-phosphate 4-kinase / 1-phosphatidylinositol-5-phosphate 4-kinase activity / 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate biosynthetic process / Synthesis of PIPs in the nucleus / 1-phosphatidylinositol-4-phosphate 5-kinase activity / autophagosome-lysosome fusion / positive regulation of autophagosome assembly / megakaryocyte development / PI5P Regulates TP53 Acetylation / Synthesis of PIPs at the plasma membrane / phosphatidylinositol phosphate biosynthetic process / photoreceptor outer segment / negative regulation of insulin receptor signaling pathway / autophagosome / photoreceptor inner segment / regulation of autophagy / PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling / lysosome / protein homodimerization activity / nucleoplasm / ATP binding / plasma membrane / cytosol
Similarity search - Function
Phosphatidylinositol-4-phosphate 5-kinase / Phosphatidylinositol-4-phosphate 5-kinase, core / : / Phosphatidylinositol-4-phosphate 5-kinase, N-terminal / Phosphatidylinositol-4-phosphate 5-Kinase / Phosphatidylinositol phosphate kinase (PIPK) domain profile. / Phosphatidylinositol phosphate kinases
Similarity search - Domain/homology
Chem-U1U / Phosphatidylinositol 5-phosphate 4-kinase type-2 alpha
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.096 Å
AuthorsHarborne, S.P.D. / Howard, T.D. / Ogg, D.T.
Funding support United Kingdom, 1items
OrganizationGrant numberCountry
Other private United Kingdom
CitationJournal: Rsc Med Chem / Year: 2023
Title: Identification of ARUK2002821 as an isoform-selective PI5P4K alpha inhibitor.
Authors: Willems, H.M.G. / Edwards, S. / Boffey, H.K. / Chawner, S.J. / Green, C. / Romero, T. / Winpenny, D. / Skidmore, J. / Clarke, J.H. / Andrews, S.P.
History
DepositionJan 19, 2023Deposition site: PDBE / Processing site: PDBE
Revision 1.0Apr 26, 2023Provider: repository / Type: Initial release
Revision 1.1Jun 7, 2023Group: Database references / Category: citation / citation_author
Item: _citation.journal_volume / _citation.page_first ..._citation.journal_volume / _citation.page_first / _citation.page_last / _citation.pdbx_database_id_DOI / _citation.pdbx_database_id_PubMed / _citation.title
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 5-phosphate 4-kinase type-2 alpha
hetero molecules


Theoretical massNumber of molelcules
Total (without water)43,2382
Polymers42,8591
Non-polymers3791
Water2,252125
1
A: Phosphatidylinositol 5-phosphate 4-kinase type-2 alpha
hetero molecules

A: Phosphatidylinositol 5-phosphate 4-kinase type-2 alpha
hetero molecules


Theoretical massNumber of molelcules
Total (without water)86,4764
Polymers85,7192
Non-polymers7582
Water362
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
crystal symmetry operation3_655-x+1,y,-z+1/21
Buried area2320 Å2
ΔGint-12 kcal/mol
Surface area28290 Å2
MethodPISA
Unit cell
Length a, b, c (Å)70.661, 84.935, 128.346
Angle α, β, γ (deg.)90.000, 90.000, 90.000
Int Tables number20
Space group name H-MC2221

-
Components

#1: Protein Phosphatidylinositol 5-phosphate 4-kinase type-2 alpha / 1-phosphatidylinositol 5-phosphate 4-kinase 2-alpha / Diphosphoinositide kinase 2-alpha / PIP5KIII ...1-phosphatidylinositol 5-phosphate 4-kinase 2-alpha / Diphosphoinositide kinase 2-alpha / PIP5KIII / Phosphatidylinositol 5-Phosphate 4-Kinase / PI5P4Kalpha / Phosphatidylinositol 5-phosphate 4-kinase type II alpha / PI(5)P 4-kinase type II alpha / PIP4KII-alpha / PtdIns(4)P-5-kinase B isoform / PtdIns(4)P-5-kinase C isoform / PtdIns(5)P-4-kinase isoform 2-alpha


Mass: 42859.383 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: PIP4K2A, PI5P4KA, PIP5K2, PIP5K2A / Production host: Escherichia coli BL21(DE3) (bacteria)
References: UniProt: P48426, 1-phosphatidylinositol-5-phosphate 4-kinase
#2: Chemical ChemComp-U1U / ~{N}-(3-chloranyl-4-methoxy-phenyl)-7-(3,4-dimethylphenyl)pyrrolo[2,3-d]pyrimidin-4-amine


Mass: 378.855 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C21H19ClN4O / Feature type: SUBJECT OF INVESTIGATION
#3: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 125 / 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: 2.28 Å3/Da / Density % sol: 46.13 %
Crystal growTemperature: 293 K / Method: vapor diffusion, hanging drop
Details: 24 % PEG smear low 0.04 M CaCl 0.04 M NaFormate 0.1 M Tris pH pH 8.0

-
Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: Diamond / Beamline: I04 / Wavelength: 0.9795 Å
DetectorType: DECTRIS PILATUS 6M-F / Detector: PIXEL / Date: Apr 13, 2019
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.9795 Å / Relative weight: 1
ReflectionResolution: 2.096→42.504 Å / Num. obs: 19434 / % possible obs: 84.7 % / Redundancy: 1.9 % / Biso Wilson estimate: 38.071 Å2 / CC1/2: 0.996 / Rmerge(I) obs: 0.04 / Rpim(I) all: 0.04 / Rrim(I) all: 0.056 / Χ2: 0.89 / Net I/σ(I): 10.3
Reflection shellResolution: 2.1→2.16 Å / Redundancy: 1.9 % / Rmerge(I) obs: 0.532 / Mean I/σ(I) obs: 1.4 / Num. unique obs: 368 / CC1/2: 0.766 / Rpim(I) all: 0.532 / Rrim(I) all: 0.753 / Χ2: 0.92 / % possible all: 19.6

-
Processing

Software
NameVersionClassification
REFMAC5.8.0403refinement
xia2data reduction
Aimlessdata scaling
PHASERphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT / Resolution: 2.096→42.504 Å / Cor.coef. Fo:Fc: 0.957 / Cor.coef. Fo:Fc free: 0.918 / SU B: 17.823 / SU ML: 0.216 / Cross valid method: FREE R-VALUE / ESU R: 0.275 / ESU R Free: 0.238
Details: Hydrogens have been added in their riding positions
RfactorNum. reflection% reflection
Rfree0.2819 961 4.948 %
Rwork0.2165 18461 -
all0.22 --
obs-19422 84.206 %
Solvent computationIon probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.2 Å / Solvent model: MASK BULK SOLVENT
Displacement parametersBiso mean: 51.147 Å2
Baniso -1Baniso -2Baniso -3
1-0.964 Å2-0 Å20 Å2
2---0.161 Å2-0 Å2
3----0.803 Å2
Refinement stepCycle: LAST / Resolution: 2.096→42.504 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms2420 0 27 125 2572
Refine LS restraints
Refine-IDTypeDev idealDev ideal targetNumber
X-RAY DIFFRACTIONr_bond_refined_d0.0080.0122516
X-RAY DIFFRACTIONr_bond_other_d0.0010.0162352
X-RAY DIFFRACTIONr_angle_refined_deg1.4611.6543404
X-RAY DIFFRACTIONr_angle_other_deg0.4871.5835406
X-RAY DIFFRACTIONr_dihedral_angle_1_deg6.9265294
X-RAY DIFFRACTIONr_dihedral_angle_2_deg7.4625.38513
X-RAY DIFFRACTIONr_dihedral_angle_3_deg15.45210435
X-RAY DIFFRACTIONr_dihedral_angle_6_deg15.91210124
X-RAY DIFFRACTIONr_chiral_restr0.0650.2369
X-RAY DIFFRACTIONr_gen_planes_refined0.0070.022888
X-RAY DIFFRACTIONr_gen_planes_other0.0010.02584
X-RAY DIFFRACTIONr_nbd_refined0.2180.2545
X-RAY DIFFRACTIONr_symmetry_nbd_other0.1940.22169
X-RAY DIFFRACTIONr_nbtor_refined0.1890.21257
X-RAY DIFFRACTIONr_symmetry_nbtor_other0.0820.21347
X-RAY DIFFRACTIONr_xyhbond_nbd_refined0.1880.2107
X-RAY DIFFRACTIONr_symmetry_xyhbond_nbd_other0.040.23
X-RAY DIFFRACTIONr_symmetry_nbd_refined0.0940.214
X-RAY DIFFRACTIONr_nbd_other0.1340.267
X-RAY DIFFRACTIONr_symmetry_xyhbond_nbd_refined0.150.23
X-RAY DIFFRACTIONr_mcbond_it3.4063.9421188
X-RAY DIFFRACTIONr_mcbond_other3.4063.9431188
X-RAY DIFFRACTIONr_mcangle_it4.8487.0571478
X-RAY DIFFRACTIONr_mcangle_other4.8477.0561479
X-RAY DIFFRACTIONr_scbond_it4.0524.221328
X-RAY DIFFRACTIONr_scbond_other4.0514.2191328
X-RAY DIFFRACTIONr_scangle_it6.0327.6071926
X-RAY DIFFRACTIONr_scangle_other6.037.6061927
X-RAY DIFFRACTIONr_lrange_it7.69438.192900
X-RAY DIFFRACTIONr_lrange_other7.68137.7052884
LS refinement shell

Refine-ID: X-RAY DIFFRACTION / Total num. of bins used: 20

Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkRfactor allNum. reflection allFsc freeFsc work% reflection obs (%)WRfactor Rwork
2.096-2.150.349150.3713030.36916690.9290.89219.05330.372
2.15-2.2090.326340.3535890.35216450.9070.90637.87230.356
2.209-2.2730.458480.4799690.47915850.9130.86564.1640.508
2.273-2.3430.401580.31411800.31815410.8980.93480.33740.307
2.343-2.4190.322870.28113390.28415220.9190.94893.69250.27
2.419-2.5040.283550.24513820.24714490.9470.96299.17180.228
2.504-2.5980.29480.23213430.23413940.9360.96299.78480.213
2.598-2.7041.168551.04110571.04813500.8190.85682.37041.079
2.704-2.8230.306620.29312310.29313070.930.94798.92880.274
2.823-2.9610.399580.21211780.2212420.9140.97399.51690.2
2.961-3.120.236520.20111420.20211960.9590.97899.83280.197
3.12-3.3080.254630.20810550.21111190.9670.97899.91060.208
3.308-3.5350.29680.1979950.20310670.9430.98299.62510.201
3.535-3.8160.218520.179320.1739870.9670.98599.6960.181
3.816-4.1770.28420.1548830.169260.9590.98799.8920.168
4.177-4.6640.237420.1458020.1498450.9710.98799.88170.169
4.664-5.3750.222370.167030.1647410.9630.98499.86510.187
5.375-6.5570.298470.2365920.2416400.9510.97599.84380.272
6.557-9.1640.205240.2054900.2055150.9750.97799.80580.246
9.164-42.5040.226140.2192960.2193150.9570.9798.41270.261
Refinement TLS params.Method: refined / Origin x: 14.2046 Å / Origin y: 20.8038 Å / Origin z: 15.8287 Å
111213212223313233
T0.0183 Å20.0111 Å20.0216 Å2-0.0529 Å2-0.023 Å2--0.0944 Å2
L2.4502 °2-0.5396 °21.3814 °2-0.7699 °2-0.5949 °2--2.3938 °2
S-0.0614 Å °-0.2362 Å °0.0423 Å °0.1177 Å °0.0872 Å °0.1432 Å °-0.07 Å °-0.3093 Å °-0.0258 Å °
Refinement TLS groupSelection: ALL

+
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