[English] 日本語
Yorodumi
- PDB-1xh8: Crystal Structures of Protein Kinase B Selective Inhibitors in Co... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 1xh8
TitleCrystal Structures of Protein Kinase B Selective Inhibitors in Complex with Protein Kinase A and Mutants
Components
  • cAMP-dependent protein kinase inhibitor, alpha form
  • cAMP-dependent protein kinase, alpha-catalytic subunit
KeywordsTRANSFERASE/TRANSFERASE INHIBITOR / PKA / kinase-inhibitor-complex / serine/threonine-protein kinase / balanol derivative / TRANSFERASE-TRANSFERASE INHIBITOR COMPLEX
Function / homology
Function and homology information


CD209 (DC-SIGN) signaling / HDL assembly / Regulation of insulin secretion / Rap1 signalling / Ion homeostasis / PKA activation in glucagon signalling / DARPP-32 events / CREB1 phosphorylation through the activation of Adenylate Cyclase / GPER1 signaling / Factors involved in megakaryocyte development and platelet production ...CD209 (DC-SIGN) signaling / HDL assembly / Regulation of insulin secretion / Rap1 signalling / Ion homeostasis / PKA activation in glucagon signalling / DARPP-32 events / CREB1 phosphorylation through the activation of Adenylate Cyclase / GPER1 signaling / Factors involved in megakaryocyte development and platelet production / Loss of Nlp from mitotic centrosomes / Recruitment of mitotic centrosome proteins and complexes / Loss of proteins required for interphase microtubule organization from the centrosome / Anchoring of the basal body to the plasma membrane / AURKA Activation by TPX2 / RET signaling / Interleukin-3, Interleukin-5 and GM-CSF signaling / Recruitment of NuMA to mitotic centrosomes / negative regulation of cAMP-dependent protein kinase activity / VEGFA-VEGFR2 Pathway / PKA activation / Hedgehog 'off' state / MAPK6/MAPK4 signaling / GLI3 is processed to GLI3R by the proteasome / Regulation of PLK1 Activity at G2/M Transition / 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 / negative regulation of protein import into nucleus / cellular response to cold / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / regulation of osteoblast differentiation / sperm capacitation / High laminar flow shear stress activates signaling by PIEZO1 and PECAM1:CDH5:KDR in endothelial cells / Vasopressin regulates renal water homeostasis via Aquaporins / negative regulation of glycolytic process through fructose-6-phosphate / Mitochondrial protein degradation / ciliary base / protein kinase A regulatory subunit binding / protein kinase A catalytic subunit binding / mesoderm formation / sperm flagellum / plasma membrane raft / axoneme / postsynaptic modulation of chemical synaptic transmission / regulation of proteasomal protein catabolic process / negative regulation of TORC1 signaling / regulation of G2/M transition of mitotic cell cycle / negative regulation of smoothened signaling pathway / positive regulation of gluconeogenesis / cellular response to glucagon stimulus / protein serine/threonine/tyrosine kinase activity / protein export from nucleus / acrosomal vesicle / positive regulation of protein export from nucleus / neural tube closure / positive regulation of cholesterol biosynthetic process / cellular response to glucose stimulus / adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway / neuromuscular junction / positive regulation of insulin secretion / adenylate cyclase-activating G protein-coupled receptor signaling pathway / mRNA processing / manganese ion binding / cellular response to heat / peptidyl-serine phosphorylation / regulation of cell cycle / protein kinase activity / postsynapse / nuclear speck / protein phosphorylation / protein domain specific binding / protein serine kinase activity / protein serine/threonine kinase activity / centrosome / ubiquitin protein ligase binding / protein kinase binding / perinuclear region of cytoplasm / glutamatergic synapse / negative regulation of transcription by RNA polymerase II / magnesium ion binding / signal transduction / mitochondrion / ATP binding / nucleus / cytosol / cytoplasm
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 / Serine/threonine-protein kinase, active site / Serine/Threonine protein kinases active-site signature. / Phosphorylase Kinase; 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 / Serine/threonine-protein kinase, active site / Serine/Threonine protein kinases active-site signature. / Phosphorylase Kinase; domain 1 / 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 / 2-Layer Sandwich / Orthogonal Bundle / Mainly Alpha / Alpha Beta
Similarity search - Domain/homology
Chem-R55 / cAMP-dependent protein kinase catalytic subunit alpha / cAMP-dependent protein kinase inhibitor alpha
Similarity search - Component
Biological speciesBos taurus (domestic cattle)
synthetic construct (others)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 1.6 Å
AuthorsBreitenlechner, C.B. / Friebe, W.-G. / Brunet, E. / Werner, G. / Graul, K. / Thomas, U. / Kuenkele, K.-P. / Schaefer, W. / Gassel, M. / Bossemeyer, D. ...Breitenlechner, C.B. / Friebe, W.-G. / Brunet, E. / Werner, G. / Graul, K. / Thomas, U. / Kuenkele, K.-P. / Schaefer, W. / Gassel, M. / Bossemeyer, D. / Huber, R. / Engh, R.A. / Masjost, B.
Citation
Journal: J.Med.Chem. / Year: 2005
Title: Design and crystal structures of protein kinase B-selective inhibitors in complex with protein kinase A and mutants
Authors: Breitenlechner, C.B. / Friebe, W.-G. / Brunet, E. / Werner, G. / Graul, K. / Thomas, U. / Kuenkele, K.-P. / Schaefer, W. / Gassel, M. / Bossemeyer, D. / Huber, R. / Engh, R.A. / Masjost, B.
#1: Journal: J.Med.Chem. / Year: 2004
Title: Structure-based optimization of novel azepane derivatives as PKB inhibitors
Authors: Breitenlechner, C.B. / Wegge, T. / Berillon, L. / Graul, K. / Marzenell, K. / Friebe, W.-G. / Thomas, U. / Schumacher, R. / Huber, R. / Engh, R.A. / Masjost, B.
History
DepositionSep 17, 2004Deposition site: RCSB / Processing site: PDBJ
Revision 1.0Sep 17, 2005Provider: repository / Type: Initial release
Revision 1.1Apr 30, 2008Group: Version format compliance
Revision 1.2Jul 13, 2011Group: Version format compliance
Revision 1.3Jun 26, 2024Group: Advisory / Data collection ...Advisory / Data collection / Database references / Derived calculations / Source and taxonomy
Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / database_2 / pdbx_distant_solvent_atoms / pdbx_entity_src_syn / pdbx_struct_assembly / pdbx_struct_assembly_gen / pdbx_struct_assembly_prop / struct_conn / struct_ref_seq_dif / struct_site
Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession ..._database_2.pdbx_DOI / _database_2.pdbx_database_accession / _pdbx_entity_src_syn.ncbi_taxonomy_id / _pdbx_entity_src_syn.organism_scientific / _struct_conn.pdbx_leaving_atom_flag / _struct_ref_seq_dif.details / _struct_site.pdbx_auth_asym_id / _struct_site.pdbx_auth_comp_id / _struct_site.pdbx_auth_seq_id
Revision 1.4Nov 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, alpha-catalytic subunit
B: cAMP-dependent protein kinase inhibitor, alpha form
hetero molecules


Theoretical massNumber of molelcules
Total (without water)43,5033
Polymers42,9332
Non-polymers5701
Water7,170398
1


  • Idetical with deposited unit
  • defined by author&software
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area3150 Å2
ΔGint-19 kcal/mol
Surface area16540 Å2
MethodPISA
Unit cell
Length a, b, c (Å)70.658, 73.111, 78.150
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, alpha-catalytic subunit / Protein Kinase A / PKA C-alpha


Mass: 40706.418 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Bos taurus (domestic cattle) / Gene: PRKACA / Plasmid: pT7-7 / Species (production host): Escherichia coli / Production host: Escherichia coli BL21(DE3) (bacteria) / Strain (production host): BL21DE3 / References: UniProt: P00517, EC: 2.7.1.37
#2: Protein/peptide cAMP-dependent protein kinase inhibitor, alpha form / Protein Kinase Inhibitor Peptide / PKI-alpha / cAMP-dependent protein kinase inhibitor / muscle/brain isoform


Mass: 2226.411 Da / Num. of mol.: 1 / Fragment: PKI(residues 5-24) / Source method: obtained synthetically / Details: Peptide synthesis / Source: (synth.) synthetic construct (others) / References: UniProt: P61925
#3: Chemical ChemComp-R55 / N-[4-({4-[5-(4,4-DIMETHYLPIPERIDIN-1-YL)-2-HYDROXYBENZOYL]BENZOYL}AMINO)AZEPAN-3-YL]ISONICOTINAMIDE


Mass: 569.694 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C33H39N5O4
#4: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 398 / 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: 2.32 Å3/Da / Density % sol: 47 %
Crystal growTemperature: 278 K / Method: vapor diffusion, hanging drop / pH: 6.4
Details: LiCl, MesBisTris, methanol, MEGA-8, pH 6.4, VAPOR DIFFUSION, HANGING DROP, temperature 278K

-
Data collection

DiffractionMean temperature: 100 K
Diffraction sourceSource: SYNCHROTRON / Site: MPG/DESY, HAMBURG / Beamline: BW6 / Wavelength: 1.00076 Å
DetectorType: MARRESEARCH / Detector: CCD / Date: Nov 25, 2002
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1.00076 Å / Relative weight: 1
ReflectionResolution: 1.6→22.53 Å / Num. all: 46943 / Num. obs: 46943

-
Processing

Software
NameVersionClassification
REFMAC5.1.24refinement
MOSFLMdata reduction
CCP4(SCALA)data scaling
AMoREphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT / Resolution: 1.6→22.53 Å / Cor.coef. Fo:Fc: 0.932 / Cor.coef. Fo:Fc free: 0.904 / SU B: 1.589 / SU ML: 0.058 / Cross valid method: THROUGHOUT / ESU R: 0.111 / ESU R Free: 0.109 / Stereochemistry target values: MAXIMUM LIKELIHOOD / Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS
RfactorNum. reflection% reflectionSelection details
Rfree0.2356 2404 5.1 %RANDOM
Rwork0.19986 ---
obs0.20168 44536 92.59 %-
Solvent computationIon probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.4 Å / Solvent model: BABINET MODEL WITH MASK
Displacement parametersBiso mean: 13.429 Å2
Baniso -1Baniso -2Baniso -3
1--0.18 Å20 Å20 Å2
2---0.46 Å20 Å2
3---0.64 Å2
Refinement stepCycle: LAST / Resolution: 1.6→22.53 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms2961 0 42 398 3401
Refine LS restraints
Refine-IDTypeDev idealDev ideal targetNumber
X-RAY DIFFRACTIONr_bond_refined_d0.0140.0223082
X-RAY DIFFRACTIONr_bond_other_d0.0020.022748
X-RAY DIFFRACTIONr_angle_refined_deg1.4211.9644161
X-RAY DIFFRACTIONr_angle_other_deg0.82336405
X-RAY DIFFRACTIONr_dihedral_angle_1_deg5.385357
X-RAY DIFFRACTIONr_dihedral_angle_2_deg
X-RAY DIFFRACTIONr_dihedral_angle_3_deg
X-RAY DIFFRACTIONr_dihedral_angle_4_deg
X-RAY DIFFRACTIONr_chiral_restr0.0920.2431
X-RAY DIFFRACTIONr_gen_planes_refined0.0080.023374
X-RAY DIFFRACTIONr_gen_planes_other0.0060.02667
X-RAY DIFFRACTIONr_nbd_refined0.2150.2615
X-RAY DIFFRACTIONr_nbd_other0.2450.23156
X-RAY DIFFRACTIONr_nbtor_refined
X-RAY DIFFRACTIONr_nbtor_other0.0850.21737
X-RAY DIFFRACTIONr_xyhbond_nbd_refined0.1780.2257
X-RAY DIFFRACTIONr_xyhbond_nbd_other
X-RAY DIFFRACTIONr_metal_ion_refined
X-RAY DIFFRACTIONr_metal_ion_other
X-RAY DIFFRACTIONr_symmetry_vdw_refined0.1440.26
X-RAY DIFFRACTIONr_symmetry_vdw_other0.2880.237
X-RAY DIFFRACTIONr_symmetry_hbond_refined0.4120.236
X-RAY DIFFRACTIONr_symmetry_hbond_other
X-RAY DIFFRACTIONr_mcbond_it0.821.51787
X-RAY DIFFRACTIONr_mcbond_other
X-RAY DIFFRACTIONr_mcangle_it1.48822882
X-RAY DIFFRACTIONr_scbond_it2.35431295
X-RAY DIFFRACTIONr_scangle_it3.6814.51279
X-RAY DIFFRACTIONr_rigid_bond_restr
X-RAY DIFFRACTIONr_sphericity_free
X-RAY DIFFRACTIONr_sphericity_bonded
LS refinement shellResolution: 1.6→1.641 Å / Total num. of bins used: 20 /
RfactorNum. reflection
Rfree0.249 203
Rwork0.182 3731

+
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