[English] 日本語
Yorodumi
- PDB-5uzk: Crystal Structure of PKA bound to an pyrrolo pyridine inhibitor -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 5uzk
TitleCrystal Structure of PKA bound to an pyrrolo pyridine inhibitor
Components
  • cAMP-dependent protein kinase catalytic subunit alpha
  • cAMP-dependent protein kinase inhibitor alpha
KeywordsTransferase/Transferase Inhibitor / PHOSPHORYLATION / KINASE / 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 / mitochondrial protein catabolic process / high-density lipoprotein particle assembly / cell communication by electrical coupling involved in cardiac conduction / nucleotide-activated protein kinase complex ...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 / 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 / molecular function inhibitor activity / 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 / molecular adaptor activity / regulation of cell cycle / postsynapse
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-504 / cAMP-dependent protein kinase catalytic subunit alpha / cAMP-dependent protein kinase inhibitor alpha
Similarity search - Component
Biological speciesHomo sapiens (human)
Oryctolagus cuniculus (rabbit)
MethodX-RAY DIFFRACTION / FOURIER SYNTHESIS / Resolution: 2.3 Å
AuthorsJacobs, M.D. / Brown, K.
CitationJournal: Bioorg. Med. Chem. Lett. / Year: 2018
Title: ROCK inhibitors 3: Design, synthesis and structure-activity relationships of 7-azaindole-based Rho kinase (ROCK) inhibitors.
Authors: Bandarage, U.K. / Cao, J. / Come, J.H. / Court, J.J. / Gao, H. / Jacobs, M.D. / Marhefka, C. / Nanthakumar, S. / Green, J.
History
DepositionFeb 26, 2017Deposition site: RCSB / Processing site: RCSB
Revision 1.0Mar 7, 2018Provider: repository / Type: Initial release
Revision 1.1Jul 11, 2018Group: Data collection / Database references / Category: citation
Item: _citation.country / _citation.journal_abbrev ..._citation.country / _citation.journal_abbrev / _citation.journal_id_ASTM / _citation.journal_id_CSD / _citation.journal_id_ISSN / _citation.pdbx_database_id_DOI / _citation.year
Revision 1.2Aug 22, 2018Group: Data collection / Database references / Category: citation / citation_author
Item: _citation.journal_abbrev / _citation.journal_volume ..._citation.journal_abbrev / _citation.journal_volume / _citation.page_first / _citation.page_last / _citation.pdbx_database_id_PubMed / _citation.title
Revision 1.3Oct 4, 2023Group: 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
Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession
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 catalytic subunit alpha
I: cAMP-dependent protein kinase inhibitor alpha
hetero molecules


Theoretical massNumber of molelcules
Total (without water)43,2573
Polymers42,7822
Non-polymers4761
Water4,954275
1


  • Idetical with deposited unit
  • defined by author&software
  • Evidence: gel filtration
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area1740 Å2
ΔGint-1 kcal/mol
Surface area15810 Å2
MethodPISA
Unit cell
Length a, b, c (Å)73.170, 78.180, 80.260
Angle α, β, γ (deg.)90.000, 90.000, 90.000
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 / Fragment: kinase domain
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: 1973.177 Da / Num. of mol.: 1 / Fragment: UNP residues 6-23 / Source method: obtained synthetically / Source: (synth.) Oryctolagus cuniculus (rabbit) / References: UniProt: P61926
#3: Chemical ChemComp-504 / 2-{3-[3-(piperidin-4-yl)propoxy]phenyl}-N-[4-(1H-pyrrolo[2,3-b]pyridin-3-yl)-1,3-thiazol-2-yl]acetamide


Mass: 475.606 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C26H29N5O2S
#4: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 275 / 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: 2.69 Å3/Da / Density % sol: 54.33 % / Mosaicity: 0.21 °
Crystal growTemperature: 277 K / Method: vapor diffusion / pH: 7 / Details: 2% MPD, VAPOR DIFFUSION, HANGING DROP

-
Data collection

DiffractionMean temperature: 100 K
Diffraction sourceSource: ROTATING ANODE / Type: RIGAKU RUH3R / Wavelength: 1.54 Å
DetectorType: RIGAKU RAXIS IV / Detector: IMAGE PLATE / Date: Apr 20, 2004
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1.54 Å / Relative weight: 1
ReflectionResolution: 2.3→26.71 Å / Num. obs: 20724 / % possible obs: 99 % / Redundancy: 3.6 % / Biso Wilson estimate: 46.03 Å2 / CC1/2: 0.996 / Rmerge(I) obs: 0.063 / Rpim(I) all: 0.039 / Rrim(I) all: 0.074 / Net I/σ(I): 13.9 / Num. measured all: 73980 / Scaling rejects: 0
Reflection shell

Diffraction-ID: 1

Resolution (Å)Redundancy (%)Rmerge(I) obsCC1/2Rpim(I) allRrim(I) all% possible all
2.3-2.433.60.2850.9680.1720.33499
7.28-26.713.20.0420.9970.0270.0596.5

-
Processing

Software
NameVersionClassification
Aimless0.5.27data scaling
BUSTER2.11.7refinement
PDB_EXTRACT3.22data extraction
XDSdata reduction
RefinementMethod to determine structure: FOURIER SYNTHESIS
Starting model: pdbid 2ERZ

2erz


Resolution: 2.3→26.71 Å / Cor.coef. Fo:Fc: 0.932 / Cor.coef. Fo:Fc free: 0.892 / Rfactor Rfree error: 0 / SU R Cruickshank DPI: 0.278 / Cross valid method: THROUGHOUT / σ(F): 0 / SU R Blow DPI: 0.313 / SU Rfree Blow DPI: 0.237 / SU Rfree Cruickshank DPI: 0.23
RfactorNum. reflection% reflectionSelection details
Rfree0.253 1005 4.87 %RANDOM
Rwork0.188 ---
obs0.191 20619 98 %-
Displacement parametersBiso max: 125.41 Å2 / Biso mean: 38.9 Å2 / Biso min: 10.61 Å2
Baniso -1Baniso -2Baniso -3
1-3.7523 Å20 Å20 Å2
2---9.126 Å20 Å2
3---5.3738 Å2
Refine analyzeLuzzati coordinate error obs: 0.27 Å
Refinement stepCycle: final / Resolution: 2.3→26.71 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms2886 0 35 275 3196
Biso mean--43.64 45.02 -
Num. residues----355
Refine LS restraints
Refine-IDTypeNumberRestraint functionWeightDev ideal
X-RAY DIFFRACTIONt_dihedral_angle_d1028SINUSOIDAL2
X-RAY DIFFRACTIONt_trig_c_planes72HARMONIC2
X-RAY DIFFRACTIONt_gen_planes432HARMONIC5
X-RAY DIFFRACTIONt_it2999HARMONIC20
X-RAY DIFFRACTIONt_nbd
X-RAY DIFFRACTIONt_improper_torsion
X-RAY DIFFRACTIONt_pseud_angle
X-RAY DIFFRACTIONt_chiral_improper_torsion373SEMIHARMONIC5
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_contact3668SEMIHARMONIC4
X-RAY DIFFRACTIONt_bond_d2999HARMONIC20.01
X-RAY DIFFRACTIONt_angle_deg4057HARMONIC21.07
X-RAY DIFFRACTIONt_omega_torsion2.92
X-RAY DIFFRACTIONt_other_torsion18.11
LS refinement shellResolution: 2.3→2.42 Å / Rfactor Rfree error: 0 / Total num. of bins used: 10
RfactorNum. reflection% reflection
Rfree0.338 164 5.82 %
Rwork0.225 2652 -
all0.231 2816 -
obs--93.34 %
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)
11.09880.31110.07090.95340.61532.0812-0.00160.0345-0.05110.00030.0369-0.07670.03920.255-0.0353-0.16960.0240.002-0.01440.0292-0.174327.6052.44412.5846
20.13790.2545-0.54770.5549-1.81.2216-0.01640.06990.07120.04970.0228-0.03820.0014-0.0851-0.0064-0.03160.0455-0.02370.08350.013-0.10614.2205-1.9895-10.9155
Refinement TLS group
IDRefine-IDRefine TLS-IDSelection detailsAuth asym-IDAuth seq-ID
1X-RAY DIFFRACTION1{ A|* }A14 - 350
2X-RAY DIFFRACTION2{ I|* }I5 - 22

+
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