[English] 日本語
Yorodumi
- PDB-8oeg: PDE4B bound to MAPI compound 92a -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 8oeg
TitlePDE4B bound to MAPI compound 92a
ComponentscAMP-specific 3',5'-cyclic phosphodiesterase 4B
KeywordsHYDROLASE / HUMAN PHOSPHODIESTERASE 4B / MAPI COMPOUND
Function / homology
Function and homology information


negative regulation of adenylate cyclase-activating adrenergic receptor signaling pathway / gamma-tubulin complex / negative regulation of relaxation of cardiac muscle / 3',5'-cyclic-AMP phosphodiesterase / neutrophil homeostasis / gamma-tubulin binding / regulation of cardiac muscle cell contraction / regulation of calcium ion transmembrane transport via high voltage-gated calcium channel / voltage-gated calcium channel complex / leukocyte migration ...negative regulation of adenylate cyclase-activating adrenergic receptor signaling pathway / gamma-tubulin complex / negative regulation of relaxation of cardiac muscle / 3',5'-cyclic-AMP phosphodiesterase / neutrophil homeostasis / gamma-tubulin binding / regulation of cardiac muscle cell contraction / regulation of calcium ion transmembrane transport via high voltage-gated calcium channel / voltage-gated calcium channel complex / leukocyte migration / cAMP catabolic process / excitatory synapse / DARPP-32 events / calcium channel regulator activity / 3',5'-cyclic-GMP phosphodiesterase activity / 3',5'-cyclic-AMP phosphodiesterase activity / cAMP binding / cellular response to epinephrine stimulus / positive regulation of interleukin-2 production / cAMP-mediated signaling / neutrophil chemotaxis / Z disc / positive regulation of type II interferon production / synaptic vesicle / cellular response to xenobiotic stimulus / T cell receptor signaling pathway / cellular response to lipopolysaccharide / transmembrane transporter binding / dendritic spine / postsynaptic density / centrosome / perinuclear region of cytoplasm / metal ion binding / nucleus / cytosol
Similarity search - Function
Phosphodiesterase 4 upstream conserved regions (UCR) / Phosphodiesterase 4 upstream conserved regions (UCR) / 3'5'-cyclic nucleotide phosphodiesterase / 3'5'-cyclic nucleotide phosphodiesterase, catalytic domain / 3'5'-cyclic nucleotide phosphodiesterase, conserved site / 3'5'-cyclic nucleotide phosphodiesterase, catalytic domain superfamily / 3'5'-cyclic nucleotide phosphodiesterase / 3'5'-cyclic nucleotide phosphodiesterase domain signature. / 3'5'-cyclic nucleotide phosphodiesterase domain profile. / Metal dependent phosphohydrolases with conserved 'HD' motif. / HD/PDEase domain
Similarity search - Domain/homology
Chem-VL9 / 3',5'-cyclic-AMP phosphodiesterase 4B
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 1.89 Å
AuthorsRizzi, A. / Armani, E.
Funding support1items
OrganizationGrant numberCountry
Not funded
CitationJournal: J.Med.Chem. / Year: 2023
Title: Optimization of M 3 Antagonist-PDE4 Inhibitor (MAPI) Dual Pharmacology Molecules for the Treatment of COPD.
Authors: Rizzi, A. / Amari, G. / Pivetti, F. / Delcanale, M. / Amadei, F. / Pappani, A. / Fornasari, L. / Villetti, G. / Marchini, G. / Pisano, A.R. / Pitozzi, V. / Pittelli, M.G. / Trevisani, M. / ...Authors: Rizzi, A. / Amari, G. / Pivetti, F. / Delcanale, M. / Amadei, F. / Pappani, A. / Fornasari, L. / Villetti, G. / Marchini, G. / Pisano, A.R. / Pitozzi, V. / Pittelli, M.G. / Trevisani, M. / Salvadori, M. / Cenacchi, V. / Fioni, A. / Puccini, P. / Civelli, M. / Patacchini, R. / Baker-Glenn, C. / Van de Poel, H. / Blackaby, W. / Nash, K. / Armani, E.
History
DepositionMar 10, 2023Deposition site: PDBE / Processing site: PDBE
Revision 1.0Apr 26, 2023Provider: repository / Type: Initial release
Revision 1.1Nov 1, 2023Group: Data collection / Database references
Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / citation / citation_author
Item: _citation.journal_volume / _citation.page_first ..._citation.journal_volume / _citation.page_first / _citation.page_last / _citation.pdbx_database_id_DOI / _citation.pdbx_database_id_PubMed / _citation.title / _citation.year
Revision 1.2Nov 8, 2023Group: Database references / Category: citation
Item: _citation.journal_volume / _citation.page_first ..._citation.journal_volume / _citation.page_first / _citation.page_last / _citation.pdbx_database_id_PubMed / _citation.title

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: cAMP-specific 3',5'-cyclic phosphodiesterase 4B
hetero molecules


Theoretical massNumber of molelcules
Total (without water)49,2604
Polymers48,4431
Non-polymers8173
Water2,090116
1


  • Idetical with deposited unit
  • defined by author
  • Evidence: gel filtration
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area250 Å2
ΔGint-49 kcal/mol
Surface area15090 Å2
Unit cell
Length a, b, c (Å)95.760, 95.760, 85.460
Angle α, β, γ (deg.)90.00, 90.00, 120.00
Int Tables number152
Space group name H-MP3121

-
Components

#1: Protein cAMP-specific 3',5'-cyclic phosphodiesterase 4B / DPDE4 / PDE32


Mass: 48442.699 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: PDE4B, DPDE4 / Production host: Spodoptera frugiperda (fall armyworm)
References: UniProt: Q07343, 3',5'-cyclic-AMP phosphodiesterase
#2: Chemical ChemComp-ZN / ZINC ION


Mass: 65.409 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: Zn / Feature type: SUBJECT OF INVESTIGATION
#3: Chemical ChemComp-MG / MAGNESIUM ION


Mass: 24.305 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: Mg / Feature type: SUBJECT OF INVESTIGATION
#4: Chemical ChemComp-VL9 / [(1~{S})-2-[3,5-bis(chloranyl)-1-oxidanyl-pyridin-4-yl]-1-(3,4-dimethoxyphenyl)ethyl] 5-[[[(1~{R})-2-[[(3~{R})-1-azabicyclo[2.2.2]octan-3-yl]oxy]-2-oxidanylidene-1-phenyl-ethyl]amino]methyl]thiophene-2-carboxylate


Mass: 727.674 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C36H38Cl2N3O7S / Feature type: SUBJECT OF INVESTIGATION
#5: Water ChemComp-HOH / water / Water


Mass: 18.015 Da / Num. of mol.: 116 / Source method: isolated from a natural source / Formula: H2O
Has ligand of interestY

-
Experimental details

-
Experiment

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

-
Sample preparation

CrystalDensity Matthews: 2.34 Å3/Da / Density % sol: 47.47 %
Crystal growTemperature: 298 K / Method: vapor diffusion, hanging drop / pH: 4.6
Details: 50 mM CALCIUM ACETATE, 20% PEG 400, 100 mM SODIUM ACETATE

-
Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: Diamond / Beamline: I03 / Wavelength: 0.9763 Å
DetectorType: DECTRIS PILATUS 6M / Detector: PIXEL / Date: Apr 16, 2015
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.9763 Å / Relative weight: 1
ReflectionResolution: 1.89→85.46 Å / Num. obs: 36474 / % possible obs: 99.5 % / Redundancy: 8.4 % / CC1/2: 0.997 / Net I/σ(I): 13.8
Reflection shellResolution: 1.89→1.94 Å / Num. unique obs: 2523 / CC1/2: 0.497

-
Processing

Software
NameVersionClassification
Aimlessdata scaling
autoPROCdata processing
xia2data reduction
XDSdata reduction
pointlessdata scaling
PHASERphasing
REFMAC5.8.0107refinement
RefinementMethod to determine structure: MOLECULAR REPLACEMENT / Resolution: 1.89→83.07 Å / Cor.coef. Fo:Fc: 0.969 / Cor.coef. Fo:Fc free: 0.958 / SU B: 5.814 / SU ML: 0.075 / Cross valid method: THROUGHOUT / ESU R: 0.107 / ESU R Free: 0.108 / Stereochemistry target values: MAXIMUM LIKELIHOOD / Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS
RfactorNum. reflection% reflectionSelection details
Rfree0.19509 1771 4.9 %RANDOM
Rwork0.15774 ---
obs0.1595 34670 99.48 %-
Solvent computationIon probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.2 Å / Solvent model: MASK
Displacement parametersBiso mean: 22.371 Å2
Baniso -1Baniso -2Baniso -3
1--0.16 Å2-0.08 Å2-0 Å2
2---0.16 Å20 Å2
3---0.51 Å2
Refinement stepCycle: 1 / Resolution: 1.89→83.07 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms2714 0 51 116 2881
Refine LS restraints
Refine-IDTypeDev idealDev ideal targetNumber
X-RAY DIFFRACTIONr_bond_refined_d0.0290.0192824
X-RAY DIFFRACTIONr_bond_other_d0.0030.022636
X-RAY DIFFRACTIONr_angle_refined_deg2.4761.9593832
X-RAY DIFFRACTIONr_angle_other_deg1.30136061
X-RAY DIFFRACTIONr_dihedral_angle_1_deg6.7855335
X-RAY DIFFRACTIONr_dihedral_angle_2_deg37.225140
X-RAY DIFFRACTIONr_dihedral_angle_3_deg16.62315492
X-RAY DIFFRACTIONr_dihedral_angle_4_deg20.2681513
X-RAY DIFFRACTIONr_chiral_restr0.1720.2433
X-RAY DIFFRACTIONr_gen_planes_refined0.0140.023170
X-RAY DIFFRACTIONr_gen_planes_other0.0020.02656
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_it1.9621.9621344
X-RAY DIFFRACTIONr_mcbond_other1.8421.9581342
X-RAY DIFFRACTIONr_mcangle_it2.522.9241677
X-RAY DIFFRACTIONr_mcangle_other2.522.9271678
X-RAY DIFFRACTIONr_scbond_it3.2352.3871480
X-RAY DIFFRACTIONr_scbond_other3.2342.3891481
X-RAY DIFFRACTIONr_scangle_it
X-RAY DIFFRACTIONr_scangle_other4.9773.432156
X-RAY DIFFRACTIONr_long_range_B_refined5.716.5383401
X-RAY DIFFRACTIONr_long_range_B_other5.716.5463402
X-RAY DIFFRACTIONr_rigid_bond_restr
X-RAY DIFFRACTIONr_sphericity_free
X-RAY DIFFRACTIONr_sphericity_bonded
LS refinement shellResolution: 1.89→1.939 Å / Total num. of bins used: 20
RfactorNum. reflection% reflection
Rfree0.303 143 -
Rwork0.282 2377 -
obs--94.38 %

+
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