[English] 日本語
Yorodumi
- PDB-8vof: GI targeted CpPI4K inhibitor -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 8vof
TitleGI targeted CpPI4K inhibitor
Components
  • Isoform 2 of Phosphatidylinositol 4-kinase beta,Isoform 2 of Phosphatidylinositol 4-kinase beta,Phosphatidylinositol 4-kinase beta
  • Ras-related protein Rab-11A
KeywordsTRANSFERASE / Inhibitor complex / chimera / Cryptosporidiosis
Function / homology
Function and homology information


regulation of early endosome to recycling endosome transport / regulation of protein localization to centrosome / regulation of endocytic recycling / early endosome to recycling endosome transport / 1-phosphatidylinositol 4-kinase / 1-phosphatidylinositol 4-kinase activity / establishment of protein localization to organelle / establishment of vesicle localization / plasma membrane to endosome transport / postsynaptic recycling endosome ...regulation of early endosome to recycling endosome transport / regulation of protein localization to centrosome / regulation of endocytic recycling / early endosome to recycling endosome transport / 1-phosphatidylinositol 4-kinase / 1-phosphatidylinositol 4-kinase activity / establishment of protein localization to organelle / establishment of vesicle localization / plasma membrane to endosome transport / postsynaptic recycling endosome / positive regulation of mitotic cytokinetic process / regulation of cilium assembly / exosomal secretion / rough endoplasmic reticulum membrane / amyloid-beta clearance by transcytosis / astral microtubule organization / neurotransmitter receptor transport, endosome to postsynaptic membrane / melanosome transport / VxPx cargo-targeting to cilium / protein transmembrane transport / Synthesis of PIPs at the Golgi membrane / regulation of vesicle-mediated transport / myosin V binding / RAB geranylgeranylation / Golgi to plasma membrane protein transport / phosphatidylinositol biosynthetic process / multivesicular body assembly / protein localization to cilium / establishment of protein localization to membrane / syntaxin binding / protein localization to cell surface / TBC/RABGAPs / dynein light intermediate chain binding / lysosome organization / mitotic metaphase chromosome alignment / phosphatidylinositol-mediated signaling / exocytosis / phosphatidylinositol phosphate biosynthetic process / inner ear development / cleavage furrow / positive regulation of epithelial cell migration / mitotic spindle assembly / transport vesicle / vesicle-mediated transport / phagocytic vesicle / positive regulation of G2/M transition of mitotic cell cycle / 14-3-3 protein binding / multivesicular body / centriole / receptor-mediated endocytosis / Anchoring of the basal body to the plasma membrane / cytoplasmic vesicle membrane / small monomeric GTPase / regulation of cytokinesis / trans-Golgi network membrane / protein localization to plasma membrane / Translocation of SLC2A4 (GLUT4) to the plasma membrane / trans-Golgi network / recycling endosome / recycling endosome membrane / spindle pole / neuron projection development / Vasopressin regulates renal water homeostasis via Aquaporins / endocytic vesicle membrane / G protein activity / microtubule binding / cytoplasmic vesicle / vesicle / mitochondrial outer membrane / endosome / Golgi membrane / GTPase activity / centrosome / GTP binding / perinuclear region of cytoplasm / glutamatergic synapse / Golgi apparatus / signal transduction / protein-containing complex / extracellular exosome / ATP binding / membrane / cytosol / cytoplasm
Similarity search - Function
: / PI4KB/PIK1, accessory (PIK) domain / : / small GTPase Rab1 family profile. / 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. ...: / PI4KB/PIK1, accessory (PIK) domain / : / small GTPase Rab1 family profile. / 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 / Ran (Ras-related nuclear proteins) /TC4 subfamily of small GTPases / Rho (Ras homology) subfamily of Ras-like small GTPases / Ras subfamily of RAS small GTPases / Small GTPase / Ras family / Rab subfamily of small GTPases / Small GTP-binding protein domain / Protein kinase-like domain superfamily / P-loop containing nucleoside triphosphate hydrolase
Similarity search - Domain/homology
: / GUANOSINE-5'-DIPHOSPHATE / Ras-related protein Rab-11A / Phosphatidylinositol 4-kinase beta
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 3 Å
AuthorsKnapp, M.S. / Cuellar, C. / Mamo, M.
Funding support1items
OrganizationGrant numberCountry
Not funded
CitationJournal: Nat Microbiol / Year: 2024
Title: Cryptosporidium PI(4)K inhibitor EDI048 is a gut-restricted parasiticidal agent to treat paediatric enteric cryptosporidiosis.
Authors: Manjunatha, U.H. / Lakshminarayana, S.B. / Jumani, R.S. / Chao, A.T. / Young, J.M. / Gable, J.E. / Knapp, M. / Hanna, I. / Galarneau, J.R. / Cantwell, J. / Kulkarni, U. / Turner, M. / Lu, P. ...Authors: Manjunatha, U.H. / Lakshminarayana, S.B. / Jumani, R.S. / Chao, A.T. / Young, J.M. / Gable, J.E. / Knapp, M. / Hanna, I. / Galarneau, J.R. / Cantwell, J. / Kulkarni, U. / Turner, M. / Lu, P. / Darrell, K.H. / Watson, L.C. / Chan, K. / Patra, D. / Mamo, M. / Luu, C. / Cuellar, C. / Shaul, J. / Xiao, L. / Chen, Y.B. / Carney, S.K. / Lakshman, J. / Osborne, C.S. / Zambriski, J.A. / Aziz, N. / Sarko, C. / Diagana, T.T.
History
DepositionJan 15, 2024Deposition site: RCSB / Processing site: RCSB
Revision 1.0Sep 4, 2024Provider: repository / Type: Initial release
Revision 1.1Sep 25, 2024Group: Database references / Category: citation
Item: _citation.country / _citation.journal_abbrev ..._citation.country / _citation.journal_abbrev / _citation.journal_id_CSD / _citation.journal_id_ISSN / _citation.title / _citation.year
Revision 1.2Oct 30, 2024Group: Database references / Structure summary / Category: citation / citation_author / pdbx_entry_details
Item: _citation.pdbx_database_id_DOI / _citation.pdbx_database_id_PubMed ..._citation.pdbx_database_id_DOI / _citation.pdbx_database_id_PubMed / _citation.title / _pdbx_entry_details.has_protein_modification
Revision 1.3Nov 13, 2024Group: Database references / Category: citation / citation_author
Item: _citation.journal_volume / _citation.page_first ..._citation.journal_volume / _citation.page_first / _citation.page_last / _citation_author.identifier_ORCID

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Isoform 2 of Phosphatidylinositol 4-kinase beta,Isoform 2 of Phosphatidylinositol 4-kinase beta,Phosphatidylinositol 4-kinase beta
B: Ras-related protein Rab-11A
hetero molecules


Theoretical massNumber of molelcules
Total (without water)86,2265
Polymers85,2092
Non-polymers1,0163
Water1086
1


  • Idetical with deposited unit
  • defined by author&software
  • Evidence: gel filtration
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area3180 Å2
ΔGint-29 kcal/mol
Surface area28450 Å2
MethodPISA
Unit cell
Length a, b, c (Å)48.570, 105.224, 186.423
Angle α, β, γ (deg.)90.00, 90.00, 90.00
Int Tables number19
Space group name H-MP212121

-
Components

-
Protein , 2 types, 2 molecules AB

#1: Protein Isoform 2 of Phosphatidylinositol 4-kinase beta,Isoform 2 of Phosphatidylinositol 4-kinase beta,Phosphatidylinositol 4-kinase beta / PI4K-beta / PI4Kbeta / PtdIns 4-kinase beta / NPIK / PI4K92 / PI4KIII


Mass: 60799.918 Da / Num. of mol.: 1 / Mutation: L294A,L374Y,P597Y
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: PI4KB, PIK4CB / Production host: unidentified baculovirus
References: UniProt: Q9UBF8, 1-phosphatidylinositol 4-kinase
#2: Protein Ras-related protein Rab-11A / Rab-11 / YL8


Mass: 24409.547 Da / Num. of mol.: 1 / Mutation: Q70L
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: RAB11A, RAB11 / Production host: unidentified baculovirus / References: UniProt: P62491, small monomeric GTPase

-
Non-polymers , 4 types, 9 molecules

#3: Chemical ChemComp-A1ADE / methyl 2-chloro-5-(methyl{(8R)-3-[4-(methylcarbamoyl)phenyl]pyrazolo[1,5-a]pyridine-5-carbonyl}amino)benzoate


Mass: 476.912 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C25H21ClN4O4 / Feature type: SUBJECT OF INVESTIGATION
#4: Chemical ChemComp-SO4 / SULFATE ION


Mass: 96.063 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: SO4
#5: Chemical ChemComp-GDP / GUANOSINE-5'-DIPHOSPHATE


Type: RNA linking / Mass: 443.201 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C10H15N5O11P2 / Comment: GDP, energy-carrying molecule*YM
#6: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 6 / Source method: isolated from a natural source / Formula: H2O

-
Details

Has ligand of interestY
Has protein modificationN

-
Experimental details

-
Experiment

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

-
Sample preparation

CrystalDensity Matthews: 2.8 Å3/Da / Density % sol: 56 %
Crystal growTemperature: 294 K / Method: vapor diffusion, hanging drop / pH: 8
Details: 0.5M ammonium sulfate, 0.088M sodium citrate, 0.875M lithium sulfate, 2.4% glycerol, 2.5% ethylene glycol, 50mM HEPES pH 6.8

-
Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: APS / Beamline: 17-ID / Wavelength: 1 Å
DetectorType: DECTRIS PILATUS 6M / Detector: PIXEL / Date: Jul 18, 2019
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1 Å / Relative weight: 1
ReflectionResolution: 3→53.51 Å / Num. obs: 19983 / % possible obs: 99.8 % / Redundancy: 6.5 % / CC1/2: 0.997 / Rmerge(I) obs: 0.116 / Rpim(I) all: 0.049 / Rrim(I) all: 0.126 / Χ2: 0.82 / Net I/σ(I): 10.1 / Num. measured all: 130663
Reflection shellResolution: 3→3.16 Å / % possible obs: 99.1 % / Redundancy: 6.4 % / Rmerge(I) obs: 1.431 / Num. measured all: 18106 / Num. unique obs: 2818 / CC1/2: 0.875 / Rpim(I) all: 0.608 / Rrim(I) all: 1.557 / Χ2: 0.68 / Net I/σ(I) obs: 1.2

-
Processing

Software
NameVersionClassification
PHENIX(1.20.1_4487: ???)refinement
Aimlessdata scaling
XDSdata reduction
PHASERphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT / Resolution: 3→50.63 Å / SU ML: 0.38 / Cross valid method: FREE R-VALUE / σ(F): 1.35 / Phase error: 34.61 / Stereochemistry target values: ML
RfactorNum. reflection% reflectionSelection details
Rfree0.27 958 4.86 %Random
Rwork0.2252 ---
obs0.2274 19722 98.89 %-
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.1 Å / Solvent model: FLAT BULK SOLVENT MODEL
Refinement stepCycle: LAST / Resolution: 3→50.63 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms4874 0 67 6 4947
Refine LS restraints
Refine-IDTypeDev idealNumber
X-RAY DIFFRACTIONf_bond_d0.0025039
X-RAY DIFFRACTIONf_angle_d0.4756866
X-RAY DIFFRACTIONf_dihedral_angle_d12.2391734
X-RAY DIFFRACTIONf_chiral_restr0.04796
X-RAY DIFFRACTIONf_plane_restr0.003869
LS refinement shell
Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkRefine-ID% reflection obs (%)
3-3.160.43011380.38662537X-RAY DIFFRACTION97
3.16-3.350.36081210.32812630X-RAY DIFFRACTION99
3.35-3.610.31991330.26312646X-RAY DIFFRACTION99
3.61-3.980.30951510.21312648X-RAY DIFFRACTION99
3.98-4.550.24541370.18852674X-RAY DIFFRACTION99
4.55-5.730.25031480.20932727X-RAY DIFFRACTION100
5.73-50.630.22231300.20522902X-RAY DIFFRACTION100
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)
12.4109-0.3119-0.97822.62521.43248.0061-0.08390.36820.1304-0.15510.1284-0.04480.1742-0.02460.03241.4054-0.14080.0340.59680.01690.5682-18.7477-7.63688.6038
24.5290.0423-2.45383.34651.06123.69890.1451-0.35770.15650.0864-0.15170.2965-0.6392-0.1936-0.00021.6554-0.01820.01580.7955-0.220.666-29.6394-0.876239.5075
31.63330.1159-0.03713.64030.72612.6173-0.1372-0.5363-0.18280.50630.0345-0.00660.32780.35050.12941.32030.08860.0470.68570.03610.5065-19.3045-27.120230.1063
41.5903-0.1280.37982.28630.14738.1546-0.12290.6272-0.1943-0.901-0.00020.2219-0.8189-0.2220.29211.675-0.27030.09531.29890.20720.9583-14.6181-2.3072-34.0297
50.0466-0.5452-0.45824.19613.02342.25480.14021.3934-0.0072-1.1363-0.1481-1.05580.2012-0.25280.12961.8239-0.2183-0.0071.3165-0.02680.7134-14.999-6.9201-18.1653
61.5907-1.2713-0.43591.0810.36410.2637-0.39081.8628-0.75170.56660.88160.92880.88660.0878-0.061.7602-0.23880.1231.23280.0860.8963-12.2508-13.5567-15.9257
74.5405-1.2888-0.17923.29391.71282.81840.36131.58480.518-0.809-0.05260.29880.3539-0.8990.12131.5789-0.123-0.04171.51790.33510.6954-16.174-6.9726-32.1054
81.3129-1.2637-0.32411.88871.06481.12690.6683-0.19821.0214-1.54271.2019-1.5219-0.59760.3719-0.36551.5137-0.04850.19921.2450.06391.0867-2.42260.7684-25.9892
91.722-0.461-0.34824.4627-1.49695.5039-0.2352-0.00120.81450.48710.2134-0.5112-1.3476-0.481-0.34781.8328-0.10160.08270.89170.27640.8824-16.92265.9202-15.2108
103.0272-0.7562-0.17610.31651.04297.73220.28030.66660.4950.20630.00390.0766-0.6082-2.4954-0.57331.1342-0.08330.05161.71530.43730.776-24.3234-1.6947-17.1355
112.66541.0147-2.02613.0748-2.83632.9743-0.12620.8970.6791-0.99790.90331.1869-0.9265-1.7725-0.65341.1119-0.106-0.05361.55420.20310.6587-23.33161.592-32.2659
Refinement TLS group
IDRefine-IDRefine TLS-IDSelection details
1X-RAY DIFFRACTION1chain 'A' and (resid 127 through 307 )
2X-RAY DIFFRACTION2chain 'A' and (resid 308 through 540 )
3X-RAY DIFFRACTION3chain 'A' and (resid 541 through 782 )
4X-RAY DIFFRACTION4chain 'B' and (resid 8 through 17 )
5X-RAY DIFFRACTION5chain 'B' and (resid 18 through 32 )
6X-RAY DIFFRACTION6chain 'B' and (resid 33 through 45 )
7X-RAY DIFFRACTION7chain 'B' and (resid 46 through 67 )
8X-RAY DIFFRACTION8chain 'B' and (resid 68 through 85 )
9X-RAY DIFFRACTION9chain 'B' and (resid 86 through 146 )
10X-RAY DIFFRACTION10chain 'B' and (resid 147 through 160 )
11X-RAY DIFFRACTION11chain 'B' and (resid 161 through 179 )

+
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