[English] 日本語
Yorodumi
- PDB-7y1g: Crystal structure of human PRKACA complexed with DS01080522 -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 7y1g
TitleCrystal structure of human PRKACA complexed with DS01080522
ComponentscAMP-dependent protein kinase catalytic subunit alpha
KeywordsTRANSFERASE / SERINE/THREONINE PROTEIN KINASE / protein kinase inhibitor
Function / homology
Function and homology information


PKA-mediated phosphorylation of CREB / PKA-mediated phosphorylation of key metabolic factors / ROBO receptors bind AKAP5 / channel activator activity / HDL assembly / 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 ...PKA-mediated phosphorylation of CREB / PKA-mediated phosphorylation of key metabolic factors / ROBO receptors bind AKAP5 / channel activator activity / HDL assembly / 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 / cAMP-dependent protein kinase / regulation of protein processing / Loss of phosphorylation of MECP2 at T308 / cAMP-dependent protein kinase activity / CREB1 phosphorylation through the activation of Adenylate Cyclase / PKA activation / protein localization to lipid droplet / cAMP-dependent protein kinase complex / regulation of bicellular tight junction assembly / cellular response to parathyroid hormone stimulus / negative regulation of interleukin-2 production / cellular response to cold / regulation of osteoblast differentiation / sperm capacitation / negative regulation of glycolytic process through fructose-6-phosphate / ciliary base / Triglyceride catabolism / protein kinase A regulatory subunit binding / cAMP/PKA signal transduction / PKA activation in glucagon signalling / mesoderm formation / RET signaling / Regulation of MECP2 expression and activity / Interleukin-3, Interleukin-5 and GM-CSF signaling / sperm flagellum / plasma membrane raft / DARPP-32 events / regulation of cardiac muscle contraction / regulation of cardiac conduction / regulation of macroautophagy / regulation of cardiac muscle contraction by regulation of the release of sequestered calcium ion / postsynaptic modulation of chemical synaptic transmission / renal water homeostasis / Hedgehog 'off' state / Ion homeostasis / regulation of proteasomal protein catabolic process / negative regulation of TORC1 signaling / Loss of Nlp from mitotic centrosomes / Loss of proteins required for interphase microtubule organization from the centrosome / sperm midpiece / Recruitment of mitotic centrosome proteins and complexes / cellular response to epinephrine stimulus / calcium channel complex / negative regulation of smoothened signaling pathway / Mitochondrial protein degradation / Recruitment of NuMA to mitotic centrosomes / positive regulation of gluconeogenesis / Anchoring of the basal body to the plasma membrane / CD209 (DC-SIGN) signaling / cellular response to glucagon stimulus / protein serine/threonine/tyrosine kinase activity / positive regulation of calcium-mediated signaling / FCGR3A-mediated IL10 synthesis / regulation of heart rate / protein export from nucleus / AURKA Activation by TPX2 / acrosomal vesicle / positive regulation of protein export from nucleus / Regulation of insulin secretion / neural tube closure / Degradation of GLI1 by the proteasome / positive regulation of cholesterol biosynthetic process / Degradation of GLI2 by the proteasome / GLI3 is processed to GLI3R by the proteasome / cellular response to glucose stimulus / MAPK6/MAPK4 signaling / adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway / neuromuscular junction / positive regulation of insulin secretion / cytokine-mediated signaling pathway / VEGFA-VEGFR2 Pathway / adenylate cyclase-activating G protein-coupled receptor signaling pathway / mRNA processing / Vasopressin regulates renal water homeostasis via Aquaporins / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / ADORA2B mediated anti-inflammatory cytokines production / Regulation of PLK1 Activity at G2/M Transition / GPER1 signaling / manganese ion binding / Factors involved in megakaryocyte development and platelet production / cellular response to heat / peptidyl-serine phosphorylation / High laminar flow shear stress activates signaling by PIEZO1 and PECAM1:CDH5:KDR in endothelial cells / regulation of cell cycle / protein kinase activity / postsynapse / nuclear speck / mitochondrial matrix / protein phosphorylation
Similarity search - Function
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. / Transferase(Phosphotransferase) domain 1 / Transferase(Phosphotransferase); domain 1 / Protein kinase domain / Serine/Threonine protein kinases, catalytic 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. / Transferase(Phosphotransferase) domain 1 / Transferase(Phosphotransferase); domain 1 / 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 / Orthogonal Bundle / Mainly Alpha
Similarity search - Domain/homology
Chem-I5G / cAMP-dependent protein kinase catalytic subunit alpha
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / MOLECULAR REPLACEMENT / Resolution: 2.3 Å
AuthorsSuzuki, M. / Ubukata, O. / Toyoda, A.
Funding support1items
OrganizationGrant numberCountry
Not funded
CitationJournal: Biochem.Biophys.Res.Commun. / Year: 2022
Title: Novel protein kinase cAMP-Activated Catalytic Subunit Alpha (PRKACA) inhibitor shows anti-tumor activity in a fibrolamellar hepatocellular carcinoma model.
Authors: Toyota, A. / Goto, M. / Miyamoto, M. / Nagashima, Y. / Iwasaki, S. / Komatsu, T. / Momose, T. / Yoshida, K. / Tsukada, T. / Matsufuji, T. / Ohno, A. / Suzuki, M. / Ubukata, O. / Kaneta, Y.
History
DepositionJun 8, 2022Deposition site: PDBJ / Processing site: PDBJ
Revision 1.0Sep 28, 2022Provider: repository / Type: Initial release
Revision 1.1Apr 3, 2024Group: Data collection / Refinement description
Category: chem_comp_atom / chem_comp_bond / pdbx_initial_refinement_model
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: cAMP-dependent protein kinase catalytic subunit alpha
B: cAMP-dependent protein kinase catalytic subunit alpha
hetero molecules


Theoretical massNumber of molelcules
Total (without water)82,6255
Polymers81,6172
Non-polymers1,0083
Water4,594255
1
A: cAMP-dependent protein kinase catalytic subunit alpha
hetero molecules


Theoretical massNumber of molelcules
Total (without water)41,2802
Polymers40,8091
Non-polymers4711
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area0 Å2
ΔGint0 kcal/mol
Surface area15530 Å2
MethodPISA
2
B: cAMP-dependent protein kinase catalytic subunit alpha
hetero molecules


Theoretical massNumber of molelcules
Total (without water)41,3453
Polymers40,8091
Non-polymers5372
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area90 Å2
ΔGint-27 kcal/mol
Surface area15620 Å2
MethodPISA
Unit cell
Length a, b, c (Å)92.221, 87.630, 113.476
Angle α, β, γ (deg.)90.000, 106.720, 90.000
Int Tables number5
Space group name H-MC121

-
Components

#1: Protein cAMP-dependent protein kinase catalytic subunit alpha / PKA C-alpha


Mass: 40808.570 Da / Num. of mol.: 2
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: PRKACA, PKACA / Production host: Escherichia coli BL21(DE3) (bacteria) / References: UniProt: P17612, cAMP-dependent protein kinase
#2: Chemical ChemComp-I5G / 1-chloranyl-~{N}-[(~{S})-(3-chloranyl-4-cyano-phenyl)-[(2~{R},4~{S})-4-oxidanylpyrrolidin-2-yl]methyl]-7-methoxy-isoquinoline-6-carboxamide


Mass: 471.336 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C23H20Cl2N4O3 / Feature type: SUBJECT OF INVESTIGATION
#3: Chemical ChemComp-ZN / ZINC ION


Mass: 65.409 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: Zn
#4: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 255 / 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: 2.69 Å3/Da / Density % sol: 54.28 %
Crystal growTemperature: 293 K / Method: vapor diffusion, sitting drop / pH: 8.4
Details: 25 mM Tris, pH 8.4/ 20% PEG3350/ 0.05 M Zn Acetate/ 25 mM Glycine

-
Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: ROTATING ANODE / Type: RIGAKU FR-E / Wavelength: 1.5418 Å
DetectorType: RIGAKU RAXIS VII / Detector: IMAGE PLATE / Date: Jun 21, 2016
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1.5418 Å / Relative weight: 1
ReflectionResolution: 2.3→45.76 Å / Num. obs: 37695 / % possible obs: 98 % / Redundancy: 3.7 % / CC1/2: 0.993 / Rmerge(I) obs: 0.103 / Rpim(I) all: 0.062 / Rrim(I) all: 0.121 / Net I/σ(I): 5.5 / Num. measured all: 140987 / Scaling rejects: 7
Reflection shell

Diffraction-ID: 1

Resolution (Å)Redundancy (%)Rmerge(I) obsNum. measured allNum. unique obsCC1/2Rpim(I) allRrim(I) allNet I/σ(I) obs% possible all
2.3-2.383.80.8331385936570.640.4920.9680.997.2
8.91-45.763.40.02922276530.9810.0190.03516.494.5

-
Processing

Software
NameVersionClassification
Aimless0.7.7data scaling
REFMAC5.8.0267refinement
PDB_EXTRACT3.27data extraction
XDSdata reduction
REFMACphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: in house structure of same protein

Resolution: 2.3→25 Å / Cor.coef. Fo:Fc: 0.96 / Cor.coef. Fo:Fc free: 0.928 / SU B: 9.048 / SU ML: 0.199 / Cross valid method: THROUGHOUT / σ(F): 0 / ESU R: 0.296 / ESU R Free: 0.225 / Stereochemistry target values: MAXIMUM LIKELIHOOD / Details: U VALUES : REFINED INDIVIDUALLY
RfactorNum. reflection% reflectionSelection details
Rfree0.2369 1892 5 %RANDOM
Rwork0.1855 ---
obs0.1881 35784 97.69 %-
Solvent computationIon probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.2 Å / Solvent model: MASK
Displacement parametersBiso max: 133.99 Å2 / Biso mean: 35.917 Å2 / Biso min: 13.71 Å2
Baniso -1Baniso -2Baniso -3
1-1.51 Å2-0 Å2-1.55 Å2
2---0.04 Å2-0 Å2
3----0.46 Å2
Refinement stepCycle: final / Resolution: 2.3→25 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms5410 0 65 255 5730
Biso mean--33.85 36.69 -
Num. residues----673
Refine LS restraints
Refine-IDTypeDev idealDev ideal targetNumber
X-RAY DIFFRACTIONr_bond_refined_d0.0060.0125679
X-RAY DIFFRACTIONr_angle_refined_deg1.5561.6527708
X-RAY DIFFRACTIONr_dihedral_angle_1_deg6.8385677
X-RAY DIFFRACTIONr_dihedral_angle_2_deg36.03822.297296
X-RAY DIFFRACTIONr_dihedral_angle_3_deg16.91115929
X-RAY DIFFRACTIONr_dihedral_angle_4_deg22.2051530
X-RAY DIFFRACTIONr_chiral_restr0.1120.2715
X-RAY DIFFRACTIONr_gen_planes_refined0.0070.024358
LS refinement shellResolution: 2.3→2.38 Å / Rfactor Rfree error: 0 / Total num. of bins used: 15
RfactorNum. reflection% reflection
Rfree0.33 186 -
Rwork0.32 3449 -
all-3635 -
obs--96.96 %

+
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