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

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 8fec
TitleStructure of J-PKAc chimera complexed with Aplithianine derivative
Components
  • (DnaJ homolog subfamily B member 1,cAMP-dependent protein kinase catalytic subunit alpha) x 2
  • 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 / negative regulation of inclusion body assembly / HDL assembly / mitochondrial protein catabolic process / Regulation of glycolysis by fructose 2,6-bisphosphate metabolism / negative regulation of cAMP-dependent protein kinase activity / regulation of protein binding ...PKA-mediated phosphorylation of CREB / PKA-mediated phosphorylation of key metabolic factors / ROBO receptors bind AKAP5 / sperm head / negative regulation of inclusion body assembly / HDL assembly / mitochondrial protein catabolic process / Regulation of glycolysis by fructose 2,6-bisphosphate metabolism / negative regulation of cAMP-dependent protein kinase activity / regulation of protein binding / nucleotide-activated protein kinase complex / high-density lipoprotein particle assembly / Rap1 signalling / renal water homeostasis / regulation of protein processing / positive regulation of ATP-dependent activity / transcription regulator inhibitor activity / protein localization to lipid droplet / regulation of bicellular tight junction assembly / cellular response to parathyroid hormone stimulus / cell communication by electrical coupling involved in cardiac conduction / cAMP-dependent protein kinase inhibitor activity / cAMP-dependent protein kinase / cellular response to cold / Loss of phosphorylation of MECP2 at T308 / regulation of osteoblast differentiation / CREB1 phosphorylation through the activation of Adenylate Cyclase / PKA activation / sperm capacitation / cAMP-dependent protein kinase activity / ciliary base / negative regulation of glycolytic process through fructose-6-phosphate / cAMP-dependent protein kinase complex / AMP-activated protein kinase activity / negative regulation of protein import into nucleus / postsynaptic modulation of chemical synaptic transmission / cellular response to glucagon stimulus / Triglyceride catabolism / protein kinase A regulatory subunit binding / plasma membrane raft / protein kinase A catalytic subunit binding / PKA activation in glucagon signalling / ATPase activator activity / : / Regulation of MECP2 expression and activity / chaperone cofactor-dependent protein refolding / HSF1-dependent transactivation / mesoderm formation / RET signaling / DARPP-32 events / response to unfolded protein / Interleukin-3, Interleukin-5 and GM-CSF signaling / regulation of cardiac muscle contraction / regulation of cardiac conduction / Regulation of HSF1-mediated heat shock response / sperm flagellum / Attenuation phase / regulation of macroautophagy / regulation of cardiac muscle contraction by regulation of the release of sequestered calcium ion / Hedgehog 'off' state / negative regulation of smoothened signaling pathway / regulation of proteasomal protein catabolic process / regulation of cellular response to heat / protein folding chaperone / Ion homeostasis / regulation of ryanodine-sensitive calcium-release channel activity / Loss of Nlp from mitotic centrosomes / Loss of proteins required for interphase microtubule organization from the centrosome / forebrain development / positive regulation of gluconeogenesis / Recruitment of mitotic centrosome proteins and complexes / sperm midpiece / negative regulation of TORC1 signaling / Recruitment of NuMA to mitotic centrosomes / protein kinase A signaling / Mitochondrial protein degradation / calcium channel complex / Anchoring of the basal body to the plasma membrane / cellular response to epinephrine stimulus / regulation of cytosolic calcium ion concentration / regulation of G2/M transition of mitotic cell cycle / Hsp70 protein binding / HSP90 chaperone cycle for steroid hormone receptors (SHR) in the presence of ligand / protein serine/threonine/tyrosine kinase activity / protein export from nucleus / regulation of heart rate / CD209 (DC-SIGN) signaling / AURKA Activation by TPX2 / FCGR3A-mediated IL10 synthesis / positive regulation of protein export from nucleus / acrosomal vesicle / neural tube closure / Regulation of insulin secretion / cellular response to glucose stimulus / Degradation of GLI1 by the proteasome / Degradation of GLI2 by the proteasome / GLI3 is processed to GLI3R by the proteasome / MAPK6/MAPK4 signaling / neuromuscular junction / adenylate cyclase-activating G protein-coupled receptor signaling pathway
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 / dnaJ domain profile. ...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-XU0 / 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: 2.7 Å
AuthorsDu, L. / Wilson, B.A.P. / Li, N. / Martinez Fiesco, J.A. / Dalilian, M. / Wang, D. / 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 6, 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

-
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
I: cAMP-dependent protein kinase inhibitor alpha
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)100,3136
Polymers99,5574
Non-polymers7572
Water00
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)50,1973
Polymers49,8182
Non-polymers3781
Water0
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area2060 Å2
ΔGint-3 kcal/mol
Surface area20120 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)50,1173
Polymers49,7382
Non-polymers3781
Water0
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area1940 Å2
ΔGint-3 kcal/mol
Surface area20720 Å2
MethodPISA
Unit cell
Length a, b, c (Å)50.640, 59.100, 91.008
Angle α, β, γ (deg.)88.950, 86.140, 89.860
Int Tables number1
Space group name H-MP1
Space group name HallP1
Symmetry operation#1: x,y,z

-
Components

#1: Protein DnaJ homolog subfamily B member 1,cAMP-dependent protein kinase catalytic subunit alpha / DnaJ protein homolog 1 / Heat shock 40 kDa protein 1 / Heat shock protein 40 / Human DnaJ protein 1 ...DnaJ protein homolog 1 / Heat shock 40 kDa protein 1 / Heat shock protein 40 / Human DnaJ protein 1 / hDj-1 / PKA C-alpha


Mass: 47591.945 Da / Num. of mol.: 1
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 (E. coli) / Variant (production host): BL21*(DE3)
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: Protein DnaJ homolog subfamily B member 1,cAMP-dependent protein kinase catalytic subunit alpha / DnaJ protein homolog 1 / Heat shock 40 kDa protein 1 / HSP40 / Heat shock protein 40 / Human DnaJ ...DnaJ protein homolog 1 / Heat shock 40 kDa protein 1 / HSP40 / Heat shock protein 40 / Human DnaJ protein 1 / hDj-1 / PKA C-alpha


Mass: 47511.969 Da / Num. of mol.: 1
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 (E. coli) / Variant (production host): BL21*(DE3)
References: UniProt: P25685, UniProt: P17612, cAMP-dependent protein kinase
#4: Chemical ChemComp-XU0 / 6-[(6P)-6-(4-bromo-1-methyl-1H-imidazol-5-yl)-2,3-dihydro-4H-1,4-thiazin-4-yl]-7H-purine


Mass: 378.250 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C13H12BrN7S / Feature type: SUBJECT OF INVESTIGATION
Has ligand of interestY

-
Experimental details

-
Experiment

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

-
Sample preparation

CrystalDensity Matthews: 2.73 Å3/Da / Density % sol: 54.93 %
Crystal growTemperature: 277.15 K / Method: vapor diffusion, hanging drop / pH: 7.5
Details: 200 mM Lithium sulfate, 100 mM HEPES 7.5, 25% 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 17, 2022
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1 Å / Relative weight: 1
ReflectionResolution: 2.7→50.53 Å / Num. obs: 26373 / % possible obs: 91.14 % / Redundancy: 1.9 % / Biso Wilson estimate: 67.13 Å2 / CC1/2: 0.998 / Rmerge(I) obs: 0.037 / Net I/σ(I): 13.17
Reflection shellResolution: 2.7→2.797 Å / Redundancy: 1.9 % / Rmerge(I) obs: 0.322 / Mean I/σ(I) obs: 2.04 / Num. unique obs: 2715 / CC1/2: 0.878 / CC star: 0.967 / % possible all: 93.13

-
Processing

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

4wb7


Resolution: 2.7→50.53 Å / SU ML: 0.4789 / Cross valid method: FREE R-VALUE / σ(F): 1.98 / Phase error: 34.8081
Stereochemistry target values: GeoStd + Monomer Library + CDL v1.2
RfactorNum. reflection% reflection
Rfree0.2874 3583 7.49 %
Rwork0.2079 44270 -
obs0.2138 26352 82.43 %
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.1 Å / Solvent model: FLAT BULK SOLVENT MODEL
Displacement parametersBiso mean: 77.68 Å2
Refinement stepCycle: LAST / Resolution: 2.7→50.53 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms7020 0 44 0 7064
Refine LS restraints
Refine-IDTypeDev idealNumber
X-RAY DIFFRACTIONf_bond_d0.00937244
X-RAY DIFFRACTIONf_angle_d1.0629769
X-RAY DIFFRACTIONf_chiral_restr0.0526998
X-RAY DIFFRACTIONf_plane_restr0.00841256
X-RAY DIFFRACTIONf_dihedral_angle_d11.266969
LS refinement shell
Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkRefine-ID% reflection obs (%)
2.7-2.730.50191560.40051629X-RAY DIFFRACTION81.73
2.73-2.770.42671510.36771703X-RAY DIFFRACTION82.69
2.77-2.810.40811010.32821836X-RAY DIFFRACTION82.64
2.81-2.850.35171230.31341618X-RAY DIFFRACTION81.74
2.85-2.890.40251320.26621715X-RAY DIFFRACTION82.53
2.9-2.940.35291420.26461689X-RAY DIFFRACTION82.33
2.94-2.990.32331540.26461697X-RAY DIFFRACTION80.06
2.99-3.050.38031340.27731536X-RAY DIFFRACTION79.15
3.05-3.110.37891160.29131648X-RAY DIFFRACTION77.3
3.11-3.170.33271310.28181492X-RAY DIFFRACTION72.2
3.17-3.240.38051410.28711679X-RAY DIFFRACTION81.61
3.24-3.310.38121330.27281774X-RAY DIFFRACTION86.37
3.31-3.40.36621600.25071776X-RAY DIFFRACTION86.27
3.4-3.490.29031220.25131813X-RAY DIFFRACTION86.31
3.49-3.590.31681420.23031767X-RAY DIFFRACTION85.38
3.59-3.710.2611350.2191757X-RAY DIFFRACTION83.87
3.71-3.840.32771390.2161677X-RAY DIFFRACTION83.38
3.84-3.990.29621340.20241757X-RAY DIFFRACTION83.75
3.99-4.170.30441430.19831711X-RAY DIFFRACTION82.04
4.17-4.390.25081280.16911634X-RAY DIFFRACTION80.02
4.4-4.670.26181040.16331525X-RAY DIFFRACTION72.27
4.67-5.030.26831560.15561771X-RAY DIFFRACTION86.8
5.03-5.540.2451500.17931816X-RAY DIFFRACTION87.61
5.54-6.330.26721700.19531807X-RAY DIFFRACTION88.5
6.34-7.980.25341300.17161749X-RAY DIFFRACTION84.64
7.98-50.530.18281560.1481694X-RAY DIFFRACTION82.44

+
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://pdbjlvh1.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