[English] 日本語
Yorodumi
- PDB-3amb: Protein kinase A sixfold mutant model of Aurora B with inhibitor ... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 3amb
TitleProtein kinase A sixfold mutant model of Aurora B with inhibitor VX-680
Components
  • cAMP-dependent protein kinase catalytic subunit alpha
  • cAMP-dependent protein kinase inhibitor alpha
KeywordsTRANSFERASE/TRANSFERASE inhibitor / PKA / protein kinase A / surrogate / VX-680 / MK-0457 / TRANSFERASE-TRANSFERASE inhibitor complex
Function / homology
Function and homology information


PKA-mediated phosphorylation of CREB / PKA-mediated phosphorylation of key metabolic factors / ROBO receptors bind AKAP5 / HDL assembly / channel activator activity / Regulation of glycolysis by fructose 2,6-bisphosphate metabolism / negative regulation of cAMP-dependent protein kinase activity / mitochondrial protein catabolic process / high-density lipoprotein particle assembly / cell communication by electrical coupling involved in cardiac conduction ...PKA-mediated phosphorylation of CREB / PKA-mediated phosphorylation of key metabolic factors / ROBO receptors bind AKAP5 / HDL assembly / channel activator activity / Regulation of glycolysis by fructose 2,6-bisphosphate metabolism / negative regulation of cAMP-dependent protein kinase activity / mitochondrial protein catabolic process / high-density lipoprotein particle assembly / cell communication by electrical coupling involved in cardiac conduction / nucleotide-activated protein kinase complex / Rap1 signalling / cAMP-dependent protein kinase inhibitor activity / potassium channel inhibitor activity / histone H1-4S35 kinase activity / cAMP-dependent protein kinase / positive regulation of triglyceride catabolic process / cAMP-dependent protein kinase activity / negative regulation of interleukin-2 production / regulation of bicellular tight junction assembly / cAMP-dependent protein kinase complex / negative regulation of glycolytic process through fructose-6-phosphate / Loss of phosphorylation of MECP2 at T308 / CREB1 phosphorylation through the activation of Adenylate Cyclase / PKA activation / Triglyceride catabolism / sperm capacitation / regulation of osteoblast differentiation / protein kinase A regulatory subunit binding / ciliary base / protein kinase A catalytic subunit binding / intracellular potassium ion homeostasis / RET signaling / Interleukin-3, Interleukin-5 and GM-CSF signaling / PKA activation in glucagon signalling / renal water homeostasis / Regulation of MECP2 expression and activity / DARPP-32 events / regulation of cardiac conduction / plasma membrane raft / cAMP/PKA signal transduction / regulation of cardiac muscle contraction / postsynaptic modulation of chemical synaptic transmission / sperm flagellum / vascular endothelial cell response to laminar fluid shear stress / positive regulation of gluconeogenesis / negative regulation of cAMP/PKA signal transduction / Hedgehog 'off' state / positive regulation of calcium-mediated signaling / regulation of macroautophagy / Ion homeostasis / regulation of heart rate / negative regulation of TORC1 signaling / regulation of cardiac muscle contraction by regulation of the release of sequestered calcium ion / Loss of Nlp from mitotic centrosomes / Loss of proteins required for interphase microtubule organization from the centrosome / protein serine/threonine/tyrosine kinase activity / Recruitment of mitotic centrosome proteins and complexes / cellular response to glucagon stimulus / cellular response to epinephrine stimulus / Recruitment of NuMA to mitotic centrosomes / calcium channel complex / Anchoring of the basal body to the plasma membrane / CD209 (DC-SIGN) signaling / positive regulation of phagocytosis / FCGR3A-mediated IL10 synthesis / Mitochondrial protein degradation / acrosomal vesicle / sperm midpiece / AURKA Activation by TPX2 / regulation of proteasomal protein catabolic process / negative regulation of protein localization to chromatin / lipid droplet / cellular response to glucose stimulus / positive regulation of insulin secretion / neuromuscular junction / regulation of microtubule cytoskeleton organization / Regulation of insulin secretion / positive regulation of cholesterol biosynthetic process / Degradation of GLI1 by the proteasome / VEGFA-VEGFR2 Pathway / Degradation of GLI2 by the proteasome / GLI3 is processed to GLI3R by the proteasome / MAPK6/MAPK4 signaling / cytokine-mediated signaling pathway / mRNA processing / adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway / Regulation of PLK1 Activity at G2/M Transition / Vasopressin regulates renal water homeostasis via Aquaporins / manganese ion binding / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / ADORA2B mediated anti-inflammatory cytokines production / cellular response to heat / GPER1 signaling / Factors involved in megakaryocyte development and platelet production / adenylate cyclase-activating G protein-coupled receptor signaling pathway / High laminar flow shear stress activates signaling by PIEZO1 and PECAM1:CDH5:KDR in endothelial cells / regulation of cell cycle / postsynapse / nuclear speck
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-VX6 / 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: 2.25 Å
AuthorsPflug, A. / de Oliveira, T.M. / Bossemeyer, D. / Engh, R.A.
CitationJournal: Biochem.J. / Year: 2011
Title: Mutants of protein kinase A that mimic the ATP-binding site of Aurora kinase
Authors: Pflug, A. / de Oliveira, T.M. / Bossemeyer, D. / Engh, R.A.
History
DepositionAug 18, 2010Deposition site: PDBJ / Processing site: PDBJ
Revision 1.0Aug 3, 2011Provider: repository / Type: Initial release
Revision 1.1Sep 7, 2011Group: Structure summary
Revision 1.2Dec 7, 2011Group: Database references
Revision 1.3Nov 1, 2023Group: Data collection / Database references ...Data collection / Database references / Derived calculations / Refinement description
Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / database_2 / pdbx_initial_refinement_model / 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 / _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 1.4Oct 23, 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 inhibitor alpha
hetero molecules


Theoretical massNumber of molelcules
Total (without water)43,5473
Polymers43,0832
Non-polymers4651
Water1,27971
1


  • Idetical with deposited unit
  • defined by author&software
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area1940 Å2
ΔGint-3 kcal/mol
Surface area17550 Å2
MethodPISA
Unit cell
Length a, b, c (Å)72.750, 75.240, 80.390
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 / PKA C-alpha


Mass: 40856.469 Da / Num. of mol.: 1 / Mutation: K47R, L95Q, M120L, V123A, Q181K, T183A
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: PRKACA / Plasmid: pT7-7 / Production host: Escherichia coli (E. coli) / Strain (production host): BL21(DE3) / References: UniProt: P17612, cAMP-dependent protein kinase
#2: Protein/peptide cAMP-dependent protein kinase inhibitor alpha / PKI / PKI-alpha / cAMP-dependent protein kinase inhibitor / muscle/brain isoform


Mass: 2226.411 Da / Num. of mol.: 1 / Fragment: UNP residues 6-25 / Source method: obtained synthetically / Details: the 5-24 peptide fragment of PKI was synthesized / Source: (synth.) Homo sapiens (human) / References: UniProt: P61925
#3: Chemical ChemComp-VX6 / CYCLOPROPANECARBOXYLIC ACID {4-[4-(4-METHYL-PIPERAZIN-1-YL)-6-(5-METHYL-2H-PYRAZOL-3-YLAMINO)-PYRIMIDIN-2-YLSULFANYL]-PHENYL}-AMIDE


Mass: 464.586 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C23H28N8OS / Comment: inhibitor*YM
#4: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 71 / Source method: isolated from a natural source / Formula: H2O
Has protein modificationY
Nonpolymer detailsVX-680 (MK-0457) LABELED AS VX6 WAS PURCHASED FROM SELLECK (SELLECK CHEMICALS LLC, USA).

-
Experimental details

-
Experiment

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

-
Sample preparation

CrystalDensity Matthews: 2.55 Å3/Da / Density % sol: 51.83 %
Crystal growTemperature: 277 K / Method: vapor diffusion, hanging drop / pH: 7.5
Details: 25mM Tris-HCl, 25mM NaCl, 1.5mM octanoyl-N-methylglucamide, 1mM (5-24)-PKI, 12-20% (v/v) methanol, 2-methyl-2,4-pentanediol 30%, pH 7.5, VAPOR DIFFUSION, HANGING DROP, temperature 277K

-
Data collection

DiffractionMean temperature: 100 K
Diffraction sourceSource: SYNCHROTRON / Site: BESSY / Beamline: 14.1 / Wavelength: 0.91841 Å
DetectorType: MARMOSAIC 225 mm CCD / Detector: CCD / Date: Jun 15, 2010
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.91841 Å / Relative weight: 1
ReflectionResolution: 2.25→37.62 Å / Num. all: 21590 / Num. obs: 21589 / % possible obs: 99.99 % / Redundancy: 4.1 % / Biso Wilson estimate: 25.88 Å2 / Rmerge(I) obs: 0.117 / Rsym value: 0.117 / Net I/σ(I): 5.9
Reflection shellResolution: 2.25→2.37 Å / Redundancy: 4.1 % / Rmerge(I) obs: 0.465 / Mean I/σ(I) obs: 1.6 / Rsym value: 0.465

-
Processing

Software
NameVersionClassification
MxCuBEdata collection
MOLREPphasing
REFMAC5.5.0109refinement
MOSFLMdata reduction
SCALAdata scaling
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: PDB ENTRY 1CDK

1cdk


Resolution: 2.25→36.38 Å / Cor.coef. Fo:Fc: 0.923 / Cor.coef. Fo:Fc free: 0.894 / SU B: 5.885 / SU ML: 0.152 / Cross valid method: THROUGHOUT / ESU R Free: 0.228 / Stereochemistry target values: MAXIMUM LIKELIHOOD / Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS
RfactorNum. reflection% reflectionSelection details
Rfree0.25622 1105 5.1 %RANDOM
Rwork0.21204 ---
obs0.21424 20439 99.99 %-
Solvent computationIon probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.4 Å / Solvent model: MASK
Displacement parametersBiso mean: 22.909 Å2
Baniso -1Baniso -2Baniso -3
1-0 Å20 Å20 Å2
2--0.02 Å20 Å2
3----0.01 Å2
Refinement stepCycle: LAST / Resolution: 2.25→36.38 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms2990 0 33 71 3094
Refine LS restraints
Refine-IDTypeDev idealDev ideal targetNumber
X-RAY DIFFRACTIONr_bond_refined_d0.0110.0223100
X-RAY DIFFRACTIONr_bond_other_d
X-RAY DIFFRACTIONr_angle_refined_deg1.3061.9674182
X-RAY DIFFRACTIONr_angle_other_deg
X-RAY DIFFRACTIONr_dihedral_angle_1_deg6.0245360
X-RAY DIFFRACTIONr_dihedral_angle_2_deg35.78423.831154
X-RAY DIFFRACTIONr_dihedral_angle_3_deg14.86115.054551
X-RAY DIFFRACTIONr_dihedral_angle_4_deg16.3991519
X-RAY DIFFRACTIONr_chiral_restr0.0920.2432
X-RAY DIFFRACTIONr_gen_planes_refined0.0050.0212354
X-RAY DIFFRACTIONr_gen_planes_other
X-RAY DIFFRACTIONr_nbd_refined
X-RAY DIFFRACTIONr_nbd_other
X-RAY DIFFRACTIONr_nbtor_refined
X-RAY DIFFRACTIONr_nbtor_other
X-RAY DIFFRACTIONr_xyhbond_nbd_refined
X-RAY DIFFRACTIONr_xyhbond_nbd_other
X-RAY DIFFRACTIONr_metal_ion_refined
X-RAY DIFFRACTIONr_metal_ion_other
X-RAY DIFFRACTIONr_symmetry_vdw_refined
X-RAY DIFFRACTIONr_symmetry_vdw_other
X-RAY DIFFRACTIONr_symmetry_hbond_refined
X-RAY DIFFRACTIONr_symmetry_hbond_other
X-RAY DIFFRACTIONr_symmetry_metal_ion_refined
X-RAY DIFFRACTIONr_symmetry_metal_ion_other
X-RAY DIFFRACTIONr_mcbond_it0.661.51806
X-RAY DIFFRACTIONr_mcbond_other
X-RAY DIFFRACTIONr_mcangle_it1.25622904
X-RAY DIFFRACTIONr_scbond_it1.90631294
X-RAY DIFFRACTIONr_scangle_it3.1214.51275
X-RAY DIFFRACTIONr_rigid_bond_restr
X-RAY DIFFRACTIONr_sphericity_free
X-RAY DIFFRACTIONr_sphericity_bonded
LS refinement shellResolution: 2.25→2.308 Å / Total num. of bins used: 20
RfactorNum. reflection% reflection
Rfree0.276 98 -
Rwork0.223 1474 -
obs--100 %

+
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