[English] 日本語
Yorodumi
- PDB-4ujb: Protein Kinase A in complex with an Inhibitor -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 4ujb
TitleProtein Kinase A in complex with an Inhibitor
Components
  • CAMP-DEPENDENT PROTEIN KINASE CATALYTIC SUBUNIT ALPHA
  • PEPTIDE
KeywordsTRANSFERASE
Function / homology
Function and homology information


cAMP/PKA signal transduction / 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 / negative regulation of cAMP-dependent protein kinase activity / negative regulation of cAMP/PKA signal transduction ...cAMP/PKA signal transduction / 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 / negative regulation of cAMP-dependent protein kinase activity / negative regulation of cAMP/PKA signal transduction / nucleotide-activated protein kinase complex / cell communication by electrical coupling involved in cardiac conduction / high-density lipoprotein particle assembly / Rap1 signalling / regulation of protein processing / protein localization to lipid droplet / regulation of bicellular tight junction assembly / cellular response to parathyroid hormone stimulus / regulation of osteoblast differentiation / cAMP-dependent protein kinase inhibitor activity / cAMP-dependent protein kinase / cellular response to cold / cAMP-dependent protein kinase activity / Loss of phosphorylation of MECP2 at T308 / sperm capacitation / CREB1 phosphorylation through the activation of Adenylate Cyclase / PKA activation / cAMP-dependent protein kinase complex / negative regulation of glycolytic process through fructose-6-phosphate / ciliary base / AMP-activated protein kinase activity / negative regulation of protein import into nucleus / negative regulation of interleukin-2 production / postsynaptic modulation of chemical synaptic transmission / Triglyceride catabolism / protein kinase A regulatory subunit binding / plasma membrane raft / protein kinase A catalytic subunit binding / PKA activation in glucagon signalling / Regulation of MECP2 expression and activity / mesoderm formation / RET signaling / Interleukin-3, Interleukin-5 and GM-CSF signaling / DARPP-32 events / regulation of cardiac muscle contraction / regulation of cardiac conduction / sperm flagellum / regulation of macroautophagy / renal water homeostasis / regulation of cardiac muscle contraction by regulation of the release of sequestered calcium ion / Hedgehog 'off' state / regulation of proteasomal protein catabolic process / negative regulation of smoothened signaling pathway / Ion homeostasis / Loss of Nlp from mitotic centrosomes / Loss of proteins required for interphase microtubule organization from the centrosome / Recruitment of mitotic centrosome proteins and complexes / positive regulation of gluconeogenesis / sperm midpiece / negative regulation of TORC1 signaling / Recruitment of NuMA to mitotic centrosomes / cellular response to glucagon stimulus / regulation of G2/M transition of mitotic cell cycle / Anchoring of the basal body to the plasma membrane / calcium channel complex / Mitochondrial protein degradation / cellular response to epinephrine stimulus / protein kinase A signaling / protein serine/threonine/tyrosine kinase activity / protein export from nucleus / CD209 (DC-SIGN) signaling / positive regulation of calcium-mediated signaling / regulation of heart rate / AURKA Activation by TPX2 / FCGR3A-mediated IL10 synthesis / acrosomal vesicle / positive regulation of protein export from nucleus / 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 / positive regulation of insulin secretion / adenylate cyclase-activating G protein-coupled receptor signaling pathway / cytokine-mediated signaling pathway / VEGFA-VEGFR2 Pathway / Vasopressin regulates renal water homeostasis via Aquaporins / mRNA processing / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / ADORA2B mediated anti-inflammatory cytokines production / GPER1 signaling / Regulation of PLK1 Activity at G2/M Transition / manganese ion binding / Factors involved in megakaryocyte development and platelet production / cellular response to heat / peptidyl-serine phosphorylation / dendritic spine
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. / Transferase(Phosphotransferase) domain 1 / Transferase(Phosphotransferase); domain 1 / Phosphorylase Kinase; domain 1 / 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. / Transferase(Phosphotransferase) domain 1 / Transferase(Phosphotransferase); domain 1 / Phosphorylase Kinase; domain 1 / Phosphorylase Kinase; 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-8BQ / 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: 1.949 Å
AuthorsAlam, K.A. / Engh, R.A.
CitationJournal: Chemistry / Year: 2016
Title: Addressing the Glycine-Rich Loop of Protein Kinases by a Multi-Facetted Interaction Network: Inhibition of Pka and a Pkb Mimic.
Authors: Lauber, B.S. / Hardegger, L.A. / Asraful, A.K. / Lund, B.A. / Dumele, O. / Harder, M. / Kuhn, B. / Engh, R.A. / Diederich, F.
History
DepositionApr 9, 2015Deposition site: PDBE / Processing site: PDBE
Revision 1.0Apr 13, 2016Provider: repository / Type: Initial release
Revision 2.0Jan 30, 2019Group: Atomic model / Data collection / Experimental preparation
Category: atom_site / exptl_crystal_grow
Item: _atom_site.B_iso_or_equiv / _atom_site.Cartn_x ..._atom_site.B_iso_or_equiv / _atom_site.Cartn_x / _atom_site.Cartn_y / _atom_site.Cartn_z / _atom_site.auth_atom_id / _atom_site.label_atom_id / _exptl_crystal_grow.method
Revision 2.1Feb 6, 2019Group: Data collection / Experimental preparation / Category: exptl_crystal_grow / Item: _exptl_crystal_grow.temp
Revision 2.2Jan 10, 2024Group: Data collection / Database references ...Data collection / Database references / Derived calculations / Other / Refinement description
Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / database_2 / pdbx_database_status / pdbx_initial_refinement_model / struct_conn / struct_site
Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession ..._database_2.pdbx_DOI / _database_2.pdbx_database_accession / _pdbx_database_status.status_code_sf / _struct_conn.pdbx_leaving_atom_flag / _struct_site.pdbx_auth_asym_id / _struct_site.pdbx_auth_comp_id / _struct_site.pdbx_auth_seq_id

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: CAMP-DEPENDENT PROTEIN KINASE CATALYTIC SUBUNIT ALPHA
B: PEPTIDE
hetero molecules


Theoretical massNumber of molelcules
Total (without water)43,6895
Polymers43,1152
Non-polymers5743
Water7,566420
1


  • Idetical with deposited unit
  • defined by author&software
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area3330 Å2
ΔGint-5.9 kcal/mol
Surface area16610 Å2
MethodPISA
Unit cell
Length a, b, c (Å)72.620, 75.371, 80.349
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 / PKA


Mass: 40888.547 Da / Num. of mol.: 1 / Fragment: KINASE DOMAIN, UNP RESIDUES 1-351
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) HOMO SAPIENS (human) / Production host: ESCHERICHIA COLI BL21(DE3) (bacteria) / References: UniProt: P17612, cAMP-dependent protein kinase
#2: Protein/peptide PEPTIDE


Mass: 2226.411 Da / Num. of mol.: 1 / Source method: obtained synthetically / Source: (synth.) HOMO SAPIENS (human) / References: UniProt: P61925*PLUS
#3: Chemical ChemComp-8BQ / 7-[(3S,4R)-4-(3-fluorophenyl)carbonylpyrrolidin-3-yl]-3H-quinazolin-4-one


Mass: 337.348 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C19H16FN3O2
#4: Chemical ChemComp-MPD / (4S)-2-METHYL-2,4-PENTANEDIOL


Mass: 118.174 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C6H14O2 / Comment: precipitant*YM
#5: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 420 / Source method: isolated from a natural source / Formula: H2O
Nonpolymer detailsNA (37A): NA

-
Experimental details

-
Experiment

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

-
Sample preparation

CrystalDensity Matthews: 2.56 Å3/Da / Density % sol: 52.03 % / Description: NONE
Crystal growTemperature: 277 K / Method: vapor diffusion, hanging drop
Details: 10MG/ML PROTEIN, 25MM BISTRIS/MES PH6.9, 50MM KCL, 1.5MM OCTANOYL-N-METHYLGLUCAMIDE, 1MM PROTEIN KINASE INHIBITOR PEPTIDE, VAPOR DIFFUSION, HANGING DROP, TEMPERATURE 277K

-
Data collection

DiffractionMean temperature: 100 K
Diffraction sourceSource: SYNCHROTRON / Site: BESSY / Beamline: 14.1 / Wavelength: 0.9184
DetectorDate: Oct 19, 2013
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.9184 Å / Relative weight: 1
ReflectionResolution: 1.95→43.83 Å / Num. obs: 32724 / % possible obs: 99.5 % / Observed criterion σ(I): 2 / Redundancy: 5.2 % / Biso Wilson estimate: 23.39 Å2 / Rmerge(I) obs: 0.1 / Net I/σ(I): 13.83
Reflection shellResolution: 1.95→2.02 Å / Redundancy: 5.1 % / Rmerge(I) obs: 0.8 / Mean I/σ(I) obs: 1.94 / % possible all: 98.4

-
Processing

Software
NameVersionClassification
PHENIX(PHENIX.REFINE)refinement
XDSdata reduction
XDSdata scaling
PHENIXphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: PDB ENTRY 3VQH

3vqh


Resolution: 1.949→43.83 Å / SU ML: 0.18 / σ(F): 1.36 / Phase error: 18.35 / Stereochemistry target values: ML
RfactorNum. reflection% reflection
Rfree0.19 1637 5 %
Rwork0.1546 --
obs0.1564 32721 99.48 %
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT BULK SOLVENT MODEL
Refinement stepCycle: LAST / Resolution: 1.949→43.83 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms2999 0 41 420 3460
Refine LS restraints
Refine-IDTypeDev idealNumber
X-RAY DIFFRACTIONf_bond_d0.0073125
X-RAY DIFFRACTIONf_angle_d0.944226
X-RAY DIFFRACTIONf_dihedral_angle_d14.2231152
X-RAY DIFFRACTIONf_chiral_restr0.04441
X-RAY DIFFRACTIONf_plane_restr0.005536
LS refinement shell
Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkRefine-ID% reflection obs (%)
1.9485-2.00590.28321340.24152529X-RAY DIFFRACTION98
2.0059-2.07060.28791330.21482539X-RAY DIFFRACTION100
2.0706-2.14460.2591350.20162554X-RAY DIFFRACTION100
2.1446-2.23050.23061350.18382568X-RAY DIFFRACTION100
2.2305-2.3320.21441340.16632552X-RAY DIFFRACTION100
2.332-2.45490.21211360.15462580X-RAY DIFFRACTION100
2.4549-2.60870.18331360.15452583X-RAY DIFFRACTION100
2.6087-2.81010.18271360.16172581X-RAY DIFFRACTION100
2.8101-3.09280.19311370.15112610X-RAY DIFFRACTION100
3.0928-3.54020.18731360.1432592X-RAY DIFFRACTION100
3.5402-4.45960.14811400.12442654X-RAY DIFFRACTION100
4.4596-43.84080.1581450.14052742X-RAY DIFFRACTION99
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)
10.5023-0.1648-0.22110.4339-0.42210.7329-0.00480.0248-0.0962-0.1468-0.01180.23150.1549-0.35080.03780.1487-0.0211-0.05560.248-0.01020.2357-36.51425.7599-9.9656
20.147-0.02480.0410.0973-0.18440.3488-0.06680.06070.36520.0940.10380.0938-0.2102-0.1872-0.00680.11420.01850.01730.1923-0.00630.2329-30.317419.62010.0621
30.3435-0.26660.08860.61540.11740.8-0.0018-0.05420.05220.00040.00490.13040.0279-0.175900.12170.0048-0.00220.1829-0.0180.1825-29.51938.8055-2.1238
40.3705-0.11780.16220.5399-0.26060.7698-0.01410.0144-0.1034-0.0819-0.020.02650.3013-0.056-00.1638-0.01390.0090.14-0.01420.1234-24.8701-3.5774-4.5737
50.20510.2531-0.48871.2744-0.47191.2116-0.0083-0.0524-0.2903-0.1501-0.1318-0.30670.58070.366-0.10750.3330.05920.00550.17560.03370.2069-14.4968-13.1863.6927
60.73630.1580.10950.1874-0.31110.76330.02390.0727-0.3344-0.05210.00550.15850.5639-0.16230.22140.3544-0.12090.01490.1808-0.01880.2214-32.1761-13.998-3.1127
70.5489-0.5235-0.17570.8563-0.09670.6763-0.0555-0.09060.11220.10290.0594-0.0496-0.281-0.0465-0.02910.17410.0122-0.0210.1596-0.01810.1875-27.034219.8481.9135
80.0055-0.00320.01230.0432-0.00420.02520.040.0595-0.0517-0.0288-0.12330.22450.14390.3457-0.00020.19990.01770.01380.2229-0.00770.1587-12.8889-8.269416.1186
90.13820.00920.10750.16450.05420.0979-0.1373-0.18580.15060.03250.032-0.1087-0.09330.0817-0.01390.1844-0.0078-0.00460.1450.00850.1799-13.67563.52164.4028
Refinement TLS group
IDRefine-IDRefine TLS-IDSelection details
1X-RAY DIFFRACTION1CHAIN 'A' AND (RESID 4 THROUGH 54 )
2X-RAY DIFFRACTION2CHAIN 'A' AND (RESID 55 THROUGH 81 )
3X-RAY DIFFRACTION3CHAIN 'A' AND (RESID 82 THROUGH 139 )
4X-RAY DIFFRACTION4CHAIN 'A' AND (RESID 140 THROUGH 233 )
5X-RAY DIFFRACTION5CHAIN 'A' AND (RESID 234 THROUGH 272 )
6X-RAY DIFFRACTION6CHAIN 'A' AND (RESID 273 THROUGH 316 )
7X-RAY DIFFRACTION7CHAIN 'A' AND (RESID 317 THROUGH 350 )
8X-RAY DIFFRACTION8CHAIN 'B' AND (RESID 5 THROUGH 11 )
9X-RAY DIFFRACTION9CHAIN 'B' AND (RESID 12 THROUGH 24 )

+
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