[English] 日本語
Yorodumi
- PDB-8fe2: Structure of J-PKAc chimera complexed with Aplithianine A -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 8fe2
TitleStructure of J-PKAc chimera complexed with Aplithianine A
Components
  • DnaJ homolog subfamily B member 1, cAMP-dependent protein kinase catalytic subunit alpha
  • cAMP-dependent protein kinase inhibitor alpha
KeywordsSIGNALING PROTEIN / Protein kinase A / Fibrolamellar Hepatocellular Carcinoma / Natural Product
Function / homology
Function and homology information


: / PKA-mediated phosphorylation of CREB / PKA-mediated phosphorylation of key metabolic factors / ROBO receptors bind AKAP5 / sperm head / HDL assembly / negative regulation of inclusion body assembly / channel activator activity / negative regulation of cAMP-dependent protein kinase activity / Regulation of glycolysis by fructose 2,6-bisphosphate metabolism ...: / PKA-mediated phosphorylation of CREB / PKA-mediated phosphorylation of key metabolic factors / ROBO receptors bind AKAP5 / sperm head / HDL assembly / negative regulation of inclusion body assembly / channel activator activity / negative regulation of cAMP-dependent protein kinase activity / Regulation of glycolysis by fructose 2,6-bisphosphate metabolism / mitochondrial protein catabolic process / nucleotide-activated protein kinase complex / cell communication by electrical coupling involved in cardiac conduction / high-density lipoprotein particle assembly / Rap1 signalling / negative regulation of cAMP/PKA signal transduction / cAMP-dependent protein kinase inhibitor activity / cAMP-dependent protein kinase / regulation of protein processing / cAMP-dependent protein kinase activity / protein localization to lipid droplet / cAMP-dependent protein kinase complex / regulation of bicellular tight junction assembly / cellular response to parathyroid hormone stimulus / Loss of phosphorylation of MECP2 at T308 / CREB1 phosphorylation through the activation of Adenylate Cyclase / negative regulation of interleukin-2 production / PKA activation / negative regulation of protein import into nucleus / regulation of osteoblast differentiation / cellular response to cold / sperm capacitation / negative regulation of glycolytic process through fructose-6-phosphate / Triglyceride catabolism / ciliary base / protein kinase A regulatory subunit binding / protein kinase A catalytic subunit binding / forebrain development / intracellular potassium ion homeostasis / ATPase activator activity / : / mesoderm formation / RET signaling / cAMP/PKA signal transduction / Interleukin-3, Interleukin-5 and GM-CSF signaling / plasma membrane raft / PKA activation in glucagon signalling / Regulation of MECP2 expression and activity / DARPP-32 events / Regulation of HSF1-mediated heat shock response / regulation of cardiac conduction / HSF1-dependent transactivation / regulation of macroautophagy / response to unfolded protein / regulation of cardiac muscle contraction / sperm flagellum / Attenuation phase / postsynaptic modulation of chemical synaptic transmission / regulation of cardiac muscle contraction by regulation of the release of sequestered calcium ion / vascular endothelial cell response to laminar fluid shear stress / renal water homeostasis / Hedgehog 'off' state / transcription regulator inhibitor activity / regulation of cellular response to heat / Ion homeostasis / regulation of G2/M transition of mitotic cell cycle / negative regulation of TORC1 signaling / regulation of proteasomal protein catabolic process / sperm midpiece / Hsp70 protein binding / cellular response to epinephrine stimulus / calcium channel complex / positive regulation of gluconeogenesis / protein folding chaperone / protein serine/threonine/tyrosine kinase activity / Mitochondrial protein degradation / cellular response to glucagon stimulus / Loss of Nlp from mitotic centrosomes / Loss of proteins required for interphase microtubule organization from the centrosome / Recruitment of mitotic centrosome proteins and complexes / acrosomal vesicle / CD209 (DC-SIGN) signaling / positive regulation of calcium-mediated signaling / Recruitment of NuMA to mitotic centrosomes / Anchoring of the basal body to the plasma membrane / regulation of heart rate / FCGR3A-mediated IL10 synthesis / protein export from nucleus / positive regulation of phagocytosis / HSP90 chaperone cycle for steroid hormone receptors (SHR) in the presence of ligand / AURKA Activation by TPX2 / positive regulation of protein export from nucleus / negative regulation of smoothened signaling pathway / neural tube closure / Regulation of insulin secretion / neuromuscular junction / cellular response to glucose stimulus / Degradation of GLI1 by the proteasome / positive regulation of cholesterol biosynthetic process / Degradation of GLI2 by the proteasome
Similarity search - Function
: / HSP40/DnaJ peptide-binding / Chaperone DnaJ, C-terminal / DnaJ C terminal domain / Nt-dnaJ domain signature. / DnaJ domain, conserved site / DnaJ domain / cAMP-dependent protein kinase inhibitor / cAMP-dependent protein kinase inhibitor / DnaJ molecular chaperone homology domain ...: / HSP40/DnaJ peptide-binding / Chaperone DnaJ, C-terminal / DnaJ C terminal domain / Nt-dnaJ domain signature. / DnaJ domain, conserved site / DnaJ domain / cAMP-dependent protein kinase inhibitor / cAMP-dependent protein kinase inhibitor / DnaJ molecular chaperone homology domain / dnaJ domain profile. / Chaperone J-domain superfamily / DnaJ domain / cAMP-dependent protein kinase catalytic subunit / Extension to Ser/Thr-type protein kinases / AGC-kinase, C-terminal / AGC-kinase C-terminal domain profile. / Serine/threonine-protein kinase, active site / Serine/Threonine protein kinases active-site signature. / Protein kinase domain / Serine/Threonine protein kinases, catalytic domain / Protein kinase, ATP binding site / Protein kinases ATP-binding region signature. / Protein kinase domain profile. / Protein kinase domain / Protein kinase-like domain superfamily
Similarity search - Domain/homology
Chem-XTI / cAMP-dependent protein kinase catalytic subunit alpha / DnaJ homolog subfamily B member 1 / cAMP-dependent protein kinase inhibitor alpha
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.34 Å
AuthorsDu, L. / Wilson, B.A.P. / Li, N. / Dalilian, M. / Wang, D. / Martinez Fiesco, J.A. / Smith, E.A. / Wamiru, A. / Goncharova, E.I. / Zhang, P. / O'Keefe, B.R.
Funding support United States, 1items
OrganizationGrant numberCountry
National Institutes of Health/National Cancer Institute (NIH/NCI) United States
CitationJournal: J.Nat.Prod. / Year: 2023
Title: Discovery and Synthesis of a Naturally Derived Protein Kinase Inhibitor that Selectively Inhibits Distinct Classes of Serine/Threonine Kinases.
Authors: Du, L. / Wilson, B.A.P. / Li, N. / Shah, R. / Dalilian, M. / Wang, D. / Smith, E.A. / Wamiru, A. / Goncharova, E.I. / Zhang, P. / O'Keefe, B.R.
History
DepositionDec 5, 2022Deposition site: RCSB / Processing site: RCSB
Revision 1.0Oct 18, 2023Provider: repository / Type: Initial release
Revision 1.1May 1, 2024Group: Database references / Category: citation / citation_author
Item: _citation.country / _citation.journal_abbrev ..._citation.country / _citation.journal_abbrev / _citation.journal_id_CSD / _citation.journal_id_ISSN / _citation.journal_volume / _citation.page_first / _citation.page_last / _citation.pdbx_database_id_DOI / _citation.pdbx_database_id_PubMed / _citation.title / _citation.year / _citation_author.identifier_ORCID / _citation_author.name
Revision 1.2Nov 20, 2024Group: Structure summary / Category: pdbx_entry_details / pdbx_modification_feature / Item: _pdbx_entry_details.has_protein_modification

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: DnaJ homolog subfamily B member 1, cAMP-dependent protein kinase catalytic subunit alpha
B: DnaJ homolog subfamily B member 1, cAMP-dependent protein kinase catalytic subunit alpha
I: cAMP-dependent protein kinase inhibitor alpha
J: cAMP-dependent protein kinase inhibitor alpha
hetero molecules


Theoretical massNumber of molelcules
Total (without water)100,2356
Polymers99,6374
Non-polymers5992
Water73941
1
A: DnaJ homolog subfamily B member 1, cAMP-dependent protein kinase catalytic subunit alpha
I: cAMP-dependent protein kinase inhibitor alpha
hetero molecules


Theoretical massNumber of molelcules
Total (without water)50,1183
Polymers49,8182
Non-polymers2991
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area1880 Å2
ΔGint-4 kcal/mol
Surface area20710 Å2
MethodPISA
2
B: DnaJ homolog subfamily B member 1, cAMP-dependent protein kinase catalytic subunit alpha
J: cAMP-dependent protein kinase inhibitor alpha
hetero molecules


Theoretical massNumber of molelcules
Total (without water)50,1183
Polymers49,8182
Non-polymers2991
Water362
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area1960 Å2
ΔGint-1 kcal/mol
Surface area20260 Å2
MethodPISA
Unit cell
Length a, b, c (Å)50.633, 171.782, 61.481
Angle α, β, γ (deg.)90.000, 90.070, 90.000
Int Tables number4
Space group name H-MP1211
Space group name HallP2yb
Symmetry operation#1: x,y,z
#2: -x,y+1/2,-z

-
Components

#1: Protein DnaJ homolog subfamily B member 1, cAMP-dependent protein kinase catalytic subunit alpha / DnaJ protein homolog 1 / Heat shock protein 40


Mass: 47591.945 Da / Num. of mol.: 2
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: DNAJB1, DNAJ1, HDJ1, HSPF1, PRKACA, PKACA / Production host: Escherichia coli BL21(DE3) (bacteria) / Variant (production host): Star
References: UniProt: P25685, UniProt: P17612, cAMP-dependent protein kinase
#2: Protein/peptide cAMP-dependent protein kinase inhibitor alpha / PKI-alpha / cAMP-dependent protein kinase inhibitor / muscle/brain isoform


Mass: 2226.411 Da / Num. of mol.: 2 / Source method: obtained synthetically / Source: (synth.) Homo sapiens (human) / References: UniProt: P61925
#3: Chemical ChemComp-XTI / 6-[(6M)-6-(1-methyl-1H-imidazol-5-yl)-2,3-dihydro-4H-1,4-thiazin-4-yl]-9H-purine / Aplithianine A


Mass: 299.354 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C13H13N7S / Feature type: SUBJECT OF INVESTIGATION
#4: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 41 / Source method: isolated from a natural source / Formula: H2O
Has ligand of interestY
Has protein modificationY

-
Experimental details

-
Experiment

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

-
Sample preparation

CrystalDensity Matthews: 2.68 Å3/Da / Density % sol: 54.16 %
Crystal growTemperature: 277.15 K / Method: vapor diffusion, hanging drop / pH: 7.5
Details: 200 mM Lithium sulfate, 100 mM HEPES 7.5, 20% PEG 3350

-
Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: APS / Beamline: 22-ID / Wavelength: 1 Å
DetectorType: DECTRIS EIGER X 16M / Detector: PIXEL / Date: Sep 18, 2021
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1 Å / Relative weight: 1
ReflectionResolution: 2.34→43.62 Å / Num. obs: 43344 / % possible obs: 98.49 % / Redundancy: 3.5 % / Biso Wilson estimate: 51.04 Å2 / CC1/2: 0.999 / CC star: 1 / Rmerge(I) obs: 0.045 / Rpim(I) all: 0.028 / Net I/σ(I): 17.59
Reflection shellResolution: 2.342→2.426 Å / Redundancy: 3.5 % / Rmerge(I) obs: 0.42 / Mean I/σ(I) obs: 3.54 / Num. unique obs: 4243 / CC1/2: 0.83 / CC star: 0.952 / Rpim(I) all: 0.26 / % possible all: 96.7

-
Processing

Software
NameVersionClassification
XDSdata reduction
XDSdata scaling
PHASERphasing
PHENIX1.20.1_4487refinement
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 4WB7

4wb7


Resolution: 2.34→43.62 Å / SU ML: 0.3406 / Cross valid method: FREE R-VALUE / σ(F): 1.38 / Phase error: 27.0539
Stereochemistry target values: GeoStd + Monomer Library + CDL v1.2
RfactorNum. reflection% reflection
Rfree0.2508 3873 4.59 %
Rwork0.1964 80488 -
obs0.1989 43342 96.84 %
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.1 Å / Solvent model: FLAT BULK SOLVENT MODEL
Displacement parametersBiso mean: 58.26 Å2
Refinement stepCycle: LAST / Resolution: 2.34→43.62 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms6974 0 42 41 7057
Refine LS restraints
Refine-IDTypeDev idealNumber
X-RAY DIFFRACTIONf_bond_d0.00817194
X-RAY DIFFRACTIONf_angle_d0.95859703
X-RAY DIFFRACTIONf_chiral_restr0.0511993
X-RAY DIFFRACTIONf_plane_restr0.00811244
X-RAY DIFFRACTIONf_dihedral_angle_d9.8721965
LS refinement shell
Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkRefine-ID% reflection obs (%)
2.34-2.370.30671260.28472640X-RAY DIFFRACTION89.51
2.37-2.40.33441420.2592865X-RAY DIFFRACTION96.53
2.4-2.430.34481220.25582840X-RAY DIFFRACTION95.89
2.43-2.470.31051330.25942849X-RAY DIFFRACTION95.7
2.47-2.50.30121350.25752789X-RAY DIFFRACTION95.24
2.5-2.540.33581390.25792845X-RAY DIFFRACTION94.16
2.54-2.580.34981270.2632698X-RAY DIFFRACTION90.69
2.58-2.620.26381400.26462782X-RAY DIFFRACTION96.95
2.62-2.670.29561440.25993099X-RAY DIFFRACTION99.69
2.67-2.710.41641500.26122898X-RAY DIFFRACTION99.48
2.71-2.770.39441440.2482941X-RAY DIFFRACTION99.61
2.77-2.820.29951430.24253049X-RAY DIFFRACTION99.78
2.82-2.880.28811360.23312856X-RAY DIFFRACTION99.5
2.88-2.950.32241510.21913016X-RAY DIFFRACTION99.34
2.95-3.020.26191500.23182876X-RAY DIFFRACTION98.95
3.02-3.110.27281360.21352949X-RAY DIFFRACTION98.85
3.11-3.20.29031400.23752938X-RAY DIFFRACTION97.84
3.2-3.30.24171440.23012838X-RAY DIFFRACTION96.44
3.3-3.420.30751430.22392829X-RAY DIFFRACTION95.87
3.42-3.560.28621300.2012769X-RAY DIFFRACTION94.25
3.56-3.720.25851280.19452778X-RAY DIFFRACTION92.49
3.72-3.910.24291400.18562838X-RAY DIFFRACTION95.45
3.91-4.160.23831430.17172949X-RAY DIFFRACTION99.26
4.16-4.480.1951380.1552919X-RAY DIFFRACTION99.38
4.48-4.930.18491390.15472975X-RAY DIFFRACTION99.01
4.93-5.640.22291390.16742949X-RAY DIFFRACTION98.88
5.64-7.10.23741300.18792803X-RAY DIFFRACTION95.26
7.1-43.620.18191410.14882911X-RAY DIFFRACTION97.6

+
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