[English] 日本語
Yorodumi
- PDB-6qj7: Difluorophenyl diacylhydrazides: Potent inhibitors of Serum- and ... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 6qj7
TitleDifluorophenyl diacylhydrazides: Potent inhibitors of Serum- and Glucocorticoid-inducible Kinase 1 (SGK1)
Components
  • cAMP-dependent protein kinase catalytic subunit alpha
  • cAMP-dependent protein kinase inhibitor alpha
KeywordsTRANSFERASE / cAMP-dependent protein kinase A (PKA)
Function / homology
Function and homology information


PKA-mediated phosphorylation of CREB / PKA-mediated phosphorylation of key metabolic factors / ROBO receptors bind AKAP5 / negative regulation of cAMP-dependent protein kinase activity / HDL assembly / channel activator activity / mitochondrial protein catabolic process / Regulation of glycolysis by fructose 2,6-bisphosphate metabolism / 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 / negative regulation of cAMP-dependent protein kinase activity / HDL assembly / channel activator activity / mitochondrial protein catabolic process / Regulation of glycolysis by fructose 2,6-bisphosphate metabolism / cell communication by electrical coupling involved in cardiac conduction / high-density lipoprotein particle assembly / nucleotide-activated protein kinase complex / potassium channel inhibitor activity / Rap1 signalling / cAMP-dependent protein kinase inhibitor activity / histone H1-4S35 kinase activity / cAMP-dependent protein kinase / regulation of protein processing / cAMP-dependent protein kinase activity / cellular response to parathyroid hormone stimulus / protein localization to lipid droplet / negative regulation of interleukin-2 production / regulation of bicellular tight junction assembly / cAMP-dependent protein kinase complex / negative regulation of protein import into nucleus / Loss of phosphorylation of MECP2 at T308 / dorsal/ventral neural tube patterning / CREB1 phosphorylation through the activation of Adenylate Cyclase / PKA activation / regulation of osteoblast differentiation / Triglyceride catabolism / cellular response to cold / sperm capacitation / negative regulation of glycolytic process through fructose-6-phosphate / ciliary base / protein kinase A catalytic subunit binding / protein kinase A regulatory subunit binding / intracellular potassium ion homeostasis / RET signaling / mesoderm formation / Interleukin-3, Interleukin-5 and GM-CSF signaling / PKA activation in glucagon signalling / plasma membrane raft / Regulation of MECP2 expression and activity / regulation of cardiac conduction / regulation of macroautophagy / DARPP-32 events / cAMP/PKA signal transduction / regulation of cardiac muscle contraction / sperm flagellum / negative regulation of cAMP/PKA signal transduction / vascular endothelial cell response to laminar fluid shear stress / postsynaptic modulation of chemical synaptic transmission / renal water homeostasis / Hedgehog 'off' state / regulation of G2/M transition of mitotic cell cycle / Ion homeostasis / negative regulation of protein localization to chromatin / regulation of proteasomal protein catabolic process / regulation of cardiac muscle contraction by regulation of the release of sequestered calcium ion / negative regulation of TORC1 signaling / Loss of Nlp from mitotic centrosomes / Loss of proteins required for interphase microtubule organization from the centrosome / protein serine/threonine/tyrosine kinase activity / cellular response to epinephrine stimulus / Recruitment of mitotic centrosome proteins and complexes / CD209 (DC-SIGN) signaling / calcium channel complex / cellular response to glucagon stimulus / protein export from nucleus / positive regulation of gluconeogenesis / Recruitment of NuMA to mitotic centrosomes / positive regulation of calcium-mediated signaling / Anchoring of the basal body to the plasma membrane / Mitochondrial protein degradation / acrosomal vesicle / regulation of heart rate / FCGR3A-mediated IL10 synthesis / positive regulation of phagocytosis / AURKA Activation by TPX2 / regulation of microtubule cytoskeleton organization / positive regulation of protein export from nucleus / negative regulation of smoothened signaling pathway / neuromuscular junction / neural tube closure / Regulation of insulin secretion / cellular response to glucose stimulus / positive regulation of insulin secretion / 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 / MAPK6/MAPK4 signaling / VEGFA-VEGFR2 Pathway / adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway / cytokine-mediated signaling pathway / mRNA processing / Vasopressin regulates renal water homeostasis via Aquaporins / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / Regulation of PLK1 Activity at G2/M Transition / ADORA2B mediated anti-inflammatory cytokines production
Similarity search - Function
cAMP-dependent protein kinase inhibitor / cAMP-dependent protein kinase inhibitor / cAMP-dependent protein kinase catalytic subunit / Extension to Ser/Thr-type protein kinases / AGC-kinase, C-terminal / AGC-kinase C-terminal domain profile. / Phosphorylase Kinase; domain 1 / Phosphorylase Kinase; domain 1 / Transferase(Phosphotransferase) domain 1 / Transferase(Phosphotransferase); domain 1 ...cAMP-dependent protein kinase inhibitor / cAMP-dependent protein kinase inhibitor / cAMP-dependent protein kinase catalytic subunit / Extension to Ser/Thr-type protein kinases / AGC-kinase, C-terminal / AGC-kinase C-terminal domain profile. / Phosphorylase Kinase; domain 1 / Phosphorylase Kinase; domain 1 / Transferase(Phosphotransferase) domain 1 / Transferase(Phosphotransferase); domain 1 / 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 / 2-Layer Sandwich / Orthogonal Bundle / Mainly Alpha / Alpha Beta
Similarity search - Domain/homology
Chem-J4B / cAMP-dependent protein kinase catalytic subunit alpha / cAMP-dependent protein kinase inhibitor alpha
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 1.69 Å
AuthorsGraedler, U.
CitationJournal: To Be Published
Title: Difluorophenyl diacylhydrazides: Potent inhibitors of Serum- and Glucocorticoid-inducible Kinase 1 (SGK1)
Authors: Graedler, U.
History
DepositionJan 23, 2019Deposition site: PDBE / Processing site: PDBE
Revision 1.0Feb 12, 2020Provider: repository / Type: Initial release
Revision 1.1Jan 24, 2024Group: Advisory / Data collection ...Advisory / Data collection / Database references / Refinement description
Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / database_2 / pdbx_initial_refinement_model / pdbx_unobs_or_zero_occ_atoms / software
Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession / _software.name
Revision 1.2Nov 20, 2024Group: Structure summary / Category: pdbx_entry_details / pdbx_modification_feature

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: cAMP-dependent protein kinase catalytic subunit alpha
B: cAMP-dependent protein kinase inhibitor alpha
hetero molecules


Theoretical massNumber of molelcules
Total (without water)43,3993
Polymers43,0352
Non-polymers3641
Water6,089338
1


  • Idetical with deposited unit
  • defined by author&software
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area1940 Å2
ΔGint-3 kcal/mol
Surface area16730 Å2
MethodPISA
Unit cell
Length a, b, c (Å)72.359, 75.881, 79.968
Angle α, β, γ (deg.)90.00, 90.00, 90.00
Int Tables number19
Space group name H-MP212121

-
Components

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


Mass: 40808.570 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: PRKACA, PKACA / Production host: Escherichia coli (E. coli) / References: 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.: 1
Source method: isolated from a genetically manipulated source
Details: cAMP-dependent protein kinase inhibitor alpha / Source: (gene. exp.) Homo sapiens (human) / Gene: PKIA, PRKACN1 / Production host: Escherichia coli (E. coli) / References: UniProt: P61925
#3: Chemical ChemComp-J4B / ~{N}'-[(2~{S})-2-[3,5-bis(fluoranyl)phenyl]-2-oxidanyl-ethanoyl]-2-ethyl-3-methyl-4-oxidanyl-benzohydrazide


Mass: 364.343 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C18H18F2N2O4
#4: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 338 / Source method: isolated from a natural source / Formula: H2O
Has protein modificationY

-
Experimental details

-
Experiment

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

-
Sample preparation

CrystalDensity Matthews: 2.57 Å3/Da / Density % sol: 52.09 %
Crystal growTemperature: 293 K / Method: vapor diffusion, hanging drop
Details: 5mM MES, 5mM Bis-Tris-propane, 75mM LiCl, 1mM DTT, 0.1mM EDTA, 1.4mM PKA-peptide, 1.4mM MEGA-8, 14% Et-OH as well solution

-
Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: NSLS / Beamline: X1A / Wavelength: 1 Å
DetectorType: DECTRIS PILATUS 2M / Detector: PIXEL / Date: Aug 23, 2007
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1 Å / Relative weight: 1
ReflectionResolution: 1.68→55.044 Å / Num. obs: 46905 / % possible obs: 96.4 % / Redundancy: 5.6 % / Biso Wilson estimate: 34.12 Å2 / Rmerge(I) obs: 0.2 / Net I/σ(I): 8.89
Reflection shellResolution: 1.68→1.78 Å / Rmerge(I) obs: 0.63 / Mean I/σ(I) obs: 1.3 / Num. unique obs: 5872 / % possible all: 71.4

-
Processing

Software
NameVersionClassification
BUSTER2.11.7refinement
TRUNCATEdata reduction
autoPROC1.1.7data scaling
MOLREPphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 1ATP

1atp


Resolution: 1.69→52.37 Å / Cor.coef. Fo:Fc: 0.956 / Cor.coef. Fo:Fc free: 0.951 / SU R Cruickshank DPI: 0.127 / Cross valid method: THROUGHOUT / σ(F): 0 / SU R Blow DPI: 0.136 / SU Rfree Blow DPI: 0.126 / SU Rfree Cruickshank DPI: 0.122
RfactorNum. reflection% reflectionSelection details
Rfree0.214 1870 5.15 %RANDOM
Rwork0.178 ---
obs0.179 36337 72.2 %-
Displacement parametersBiso mean: 41.29 Å2
Baniso -1Baniso -2Baniso -3
1-1.5022 Å20 Å20 Å2
2---0.3599 Å20 Å2
3----1.1424 Å2
Refine analyzeLuzzati coordinate error obs: 0.24 Å
Refinement stepCycle: 1 / Resolution: 1.69→52.37 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms2920 0 47 338 3305
Refine LS restraints
Refine-IDTypeDev idealNumberRestraint functionWeight
X-RAY DIFFRACTIONt_bond_d0.0123059HARMONIC2
X-RAY DIFFRACTIONt_angle_deg1.044131HARMONIC2
X-RAY DIFFRACTIONt_dihedral_angle_d1071SINUSOIDAL2
X-RAY DIFFRACTIONt_incorr_chiral_ct
X-RAY DIFFRACTIONt_pseud_angle
X-RAY DIFFRACTIONt_trig_c_planes
X-RAY DIFFRACTIONt_gen_planes513HARMONIC5
X-RAY DIFFRACTIONt_it3059HARMONIC20
X-RAY DIFFRACTIONt_nbd
X-RAY DIFFRACTIONt_omega_torsion3.08
X-RAY DIFFRACTIONt_other_torsion18.14
X-RAY DIFFRACTIONt_improper_torsion
X-RAY DIFFRACTIONt_chiral_improper_torsion378SEMIHARMONIC5
X-RAY DIFFRACTIONt_sum_occupancies
X-RAY DIFFRACTIONt_utility_distance
X-RAY DIFFRACTIONt_utility_angle
X-RAY DIFFRACTIONt_utility_torsion
X-RAY DIFFRACTIONt_ideal_dist_contact3766SEMIHARMONIC4
LS refinement shellResolution: 1.69→1.79 Å / Total num. of bins used: 50
RfactorNum. reflection% reflection
Rfree0.227 -4.81 %
Rwork0.2358 692 -
all0.2353 727 -
obs--8.67 %
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)
11.04950.2809-0.08521.5724-0.67532.6834-0.01140.08120.03550.15220.00570.1751-0.4906-0.16420.0056-0.07670.0393-0.0003-0.093-0.0346-0.1175-27.433-2.18662.6425
21.04290.1640.05771.5615-0.76293.91960.01430.0244-0.15640.0583-0.07840.02810.02550.07630.06410.0588-0.0408-0.0261-0.01330.0103-0.063-13.54520.9481-8.6637
Refinement TLS group
IDRefine-IDRefine TLS-IDSelection details
1X-RAY DIFFRACTION1{ A|* }
2X-RAY DIFFRACTION2{ B|* }

+
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