[English] 日本語
Yorodumi
- PDB-7cwg: Crystal structure of PDE8A catalytic domain in complex with 3a -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 7cwg
TitleCrystal structure of PDE8A catalytic domain in complex with 3a
ComponentsHigh affinity cAMP-specific and IBMX-insensitive 3',5'-cyclic phosphodiesterase 8A
KeywordsHYDROLASE / cAMP-specific / Selective PDE8A inhibitor
Function / homology
Function and homology information


3',5'-cyclic-AMP phosphodiesterase / protein kinase activator activity / cAMP catabolic process / 3',5'-cyclic-GMP phosphodiesterase activity / 3',5'-cyclic-AMP phosphodiesterase activity / cAMP-mediated signaling / cellular response to epidermal growth factor stimulus / kinase binding / G alpha (s) signalling events / positive regulation of ERK1 and ERK2 cascade ...3',5'-cyclic-AMP phosphodiesterase / protein kinase activator activity / cAMP catabolic process / 3',5'-cyclic-GMP phosphodiesterase activity / 3',5'-cyclic-AMP phosphodiesterase activity / cAMP-mediated signaling / cellular response to epidermal growth factor stimulus / kinase binding / G alpha (s) signalling events / positive regulation of ERK1 and ERK2 cascade / regulation of DNA-templated transcription / perinuclear region of cytoplasm / extracellular exosome / nucleus / metal ion binding / cytosol
Similarity search - Function
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 / PAS fold ...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 / PAS fold / PAS fold / PAS repeat profile. / PAS domain / PAS domain superfamily
Similarity search - Domain/homology
Chem-GJU / High affinity cAMP-specific and IBMX-insensitive 3',5'-cyclic phosphodiesterase 8A
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / MOLECULAR REPLACEMENT / Resolution: 2.8 Å
AuthorsHuang, Y. / Wu, X.-N. / Zhou, Q. / Wu, Y. / Luo, H.-B.
Funding support China, 2items
OrganizationGrant numberCountry
National Natural Science Foundation of China (NSFC)21877134 China
National Natural Science Foundation of China (NSFC)81522041 China
CitationJournal: J.Med.Chem. / Year: 2020
Title: Rational Design of 2-Chloroadenine Derivatives as Highly Selective Phosphodiesterase 8A Inhibitors.
Authors: Huang, Y. / Wu, X.N. / Zhou, Q. / Wu, Y. / Zheng, D. / Li, Z. / Guo, L. / Luo, H.B.
History
DepositionAug 28, 2020Deposition site: PDBJ / Processing site: PDBJ
Revision 1.0Sep 1, 2021Provider: repository / Type: Initial release
Revision 1.1Mar 16, 2022Group: Database references / Category: citation / citation_author
Item: _citation.country / _citation.journal_abbrev ..._citation.country / _citation.journal_abbrev / _citation.journal_id_ASTM / _citation.journal_id_CSD / _citation.journal_id_ISSN / _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 29, 2023Group: Data collection / Refinement description
Category: chem_comp_atom / chem_comp_bond / pdbx_initial_refinement_model
Revision 1.3Oct 16, 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: High affinity cAMP-specific and IBMX-insensitive 3',5'-cyclic phosphodiesterase 8A
hetero molecules


Theoretical massNumber of molelcules
Total (without water)39,5344
Polymers39,0901
Non-polymers4443
Water1,09961
1


  • Idetical with deposited unit
  • defined by author&software
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area90 Å2
ΔGint-33 kcal/mol
Surface area15360 Å2
MethodPISA
Unit cell
Length a, b, c (Å)75.797, 131.832, 101.335
Angle α, β, γ (deg.)90.00, 90.00, 90.00
Int Tables number20
Space group name H-MC2221

-
Components

#1: Protein High affinity cAMP-specific and IBMX-insensitive 3',5'-cyclic phosphodiesterase 8A


Mass: 39090.020 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: PDE8A / Production host: Escherichia coli BL21 (bacteria) / Strain (production host): BL21
References: UniProt: O60658, 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
#3: Chemical ChemComp-MG / MAGNESIUM ION


Mass: 24.305 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: Mg
#4: Chemical ChemComp-GJU / 9-[(1~{S})-1-[4-[2,2-bis(fluoranyl)ethoxy]pyridin-2-yl]ethyl]-2-chloranyl-purin-6-amine


Mass: 354.742 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C14H13ClF2N6O / Feature type: SUBJECT OF INVESTIGATION
#5: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 61 / Source method: isolated from a natural source / Formula: H2O
Has ligand of interestY
Has protein modificationY

-
Experimental details

-
Experiment

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

-
Sample preparation

CrystalDensity Matthews: 3.33 Å3/Da / Density meas: 63.07 Mg/m3 / Density % sol: 62.01 %
Crystal growTemperature: 277 K / Method: vapor diffusion, hanging drop
Details: 100mM Cacodylate Sodium pH 6.5, 15% Isopropanol, 30% Ethylene Glycol, 11% PEG3350

-
Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SEALED TUBE / Type: OXFORD DIFFRACTION NOVA / Wavelength: 1.5406 Å
DetectorType: OXFORD ONYX CCD / Detector: CCD / Date: Aug 12, 2020
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1.5406 Å / Relative weight: 1
ReflectionResolution: 2.8→22.35 Å / Num. obs: 20210 / % possible obs: 99.8 % / Redundancy: 9.3 % / Rmerge(I) obs: 0.157 / Net I/σ(I): 18.7
Reflection shellResolution: 2.8→3.04 Å / Redundancy: 10.8 % / Rmerge(I) obs: 0.224 / Mean I/σ(I) obs: 10.85 / Num. unique obs: 2021 / % possible all: 100

-
Processing

Software
NameVersionClassification
REFMAC6.5.0refinement
CrysalisPro38.41data reduction
CrysalisPro38.41data scaling
PHASER6.5.0phasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 3ECM

3ecm


Resolution: 2.8→22.35 Å / Cor.coef. Fo:Fc: 0.82 / Cor.coef. Fo:Fc free: 0.779 / SU B: 20.347 / SU ML: 0.412 / Cross valid method: THROUGHOUT / ESU R: 1.25 / ESU R Free: 0.431 / Stereochemistry target values: MAXIMUM LIKELIHOOD / Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS
RfactorNum. reflection% reflectionSelection details
Rfree0.31747 600 4.7 %RANDOM
Rwork0.27477 ---
obs0.27693 12213 99.7 %-
Solvent computationIon probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.2 Å / Solvent model: MASK
Displacement parametersBiso mean: 41.421 Å2
Baniso -1Baniso -2Baniso -3
1--0.13 Å2-0 Å20 Å2
2--0.06 Å2-0 Å2
3---0.07 Å2
Refinement stepCycle: 1 / Resolution: 2.8→22.35 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms2693 0 26 61 2780
Refine LS restraints
Refine-IDTypeDev idealDev ideal targetNumber
X-RAY DIFFRACTIONr_bond_refined_d0.0070.0192785
X-RAY DIFFRACTIONr_bond_other_d0.0010.022538
X-RAY DIFFRACTIONr_angle_refined_deg0.9871.9313790
X-RAY DIFFRACTIONr_angle_other_deg0.88135823
X-RAY DIFFRACTIONr_dihedral_angle_1_deg5.1745337
X-RAY DIFFRACTIONr_dihedral_angle_2_deg34.46424.46139
X-RAY DIFFRACTIONr_dihedral_angle_3_deg13.47915449
X-RAY DIFFRACTIONr_dihedral_angle_4_deg10.4541515
X-RAY DIFFRACTIONr_chiral_restr0.0550.2418
X-RAY DIFFRACTIONr_gen_planes_refined0.0040.0213277
X-RAY DIFFRACTIONr_gen_planes_other0.0010.02668
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_it0.7744.281351
X-RAY DIFFRACTIONr_mcbond_other0.7744.2781350
X-RAY DIFFRACTIONr_mcangle_it1.3876.4161687
X-RAY DIFFRACTIONr_mcangle_other1.3876.4191688
X-RAY DIFFRACTIONr_scbond_it0.4844.2171434
X-RAY DIFFRACTIONr_scbond_other0.4844.2161435
X-RAY DIFFRACTIONr_scangle_it
X-RAY DIFFRACTIONr_scangle_other0.8946.3212104
X-RAY DIFFRACTIONr_long_range_B_refined3.19733.4513284
X-RAY DIFFRACTIONr_long_range_B_other3.20533.463279
X-RAY DIFFRACTIONr_rigid_bond_restr
X-RAY DIFFRACTIONr_sphericity_free
X-RAY DIFFRACTIONr_sphericity_bonded
LS refinement shellResolution: 2.8→2.872 Å / Total num. of bins used: 20
RfactorNum. reflection% reflection
Rfree0.425 38 -
Rwork0.271 885 -
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