[English] 日本語
Yorodumi
- PDB-7xbb: Crystal structure of PDE4D catalytic domain complexed with compou... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 7xbb
TitleCrystal structure of PDE4D catalytic domain complexed with compound 23a
ComponentsIsoform 3 of cAMP-specific 3',5'-cyclic phosphodiesterase 4D
KeywordsHYDROLASE / PDE4 inhibitor
Function / homology
Function and homology information


signaling receptor regulator activity / negative regulation of heart contraction / negative regulation of relaxation of cardiac muscle / 3',5'-cyclic-AMP phosphodiesterase / positive regulation of interleukin-5 production / negative regulation of adenylate cyclase-activating G protein-coupled receptor signaling pathway / establishment of endothelial barrier / regulation of cardiac muscle cell contraction / beta-2 adrenergic receptor binding / regulation of calcium ion transmembrane transport via high voltage-gated calcium channel ...signaling receptor regulator activity / negative regulation of heart contraction / negative regulation of relaxation of cardiac muscle / 3',5'-cyclic-AMP phosphodiesterase / positive regulation of interleukin-5 production / negative regulation of adenylate cyclase-activating G protein-coupled receptor signaling pathway / establishment of endothelial barrier / regulation of cardiac muscle cell contraction / beta-2 adrenergic receptor binding / regulation of calcium ion transmembrane transport via high voltage-gated calcium channel / voltage-gated calcium channel complex / heterocyclic compound binding / positive regulation of heart rate / adrenergic receptor signaling pathway / regulation of cell communication by electrical coupling involved in cardiac conduction / negative regulation of peptidyl-serine phosphorylation / cAMP catabolic process / 3',5'-cyclic-nucleotide phosphodiesterase activity / DARPP-32 events / 3',5'-cyclic-GMP phosphodiesterase activity / calcium channel regulator activity / 3',5'-cyclic-AMP phosphodiesterase activity / cAMP binding / regulation of release of sequestered calcium ion into cytosol by sarcoplasmic reticulum / cellular response to cAMP / cAMP-mediated signaling / calcium channel complex / cellular response to epinephrine stimulus / positive regulation of interleukin-2 production / regulation of heart rate / positive regulation of type II interferon production / T cell receptor signaling pathway / ATPase binding / scaffold protein binding / G alpha (s) signalling events / transmembrane transporter binding / apical plasma membrane / centrosome / perinuclear region of cytoplasm / enzyme binding / membrane / nucleus / metal ion binding / plasma membrane / 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.
Similarity search - Domain/homology
Chem-B6V / 3',5'-cyclic-AMP phosphodiesterase 4D
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / MOLECULAR REPLACEMENT / Resolution: 2.10000900931 Å
AuthorsHuang, Y.-Y. / Luo, H.-B.
Funding support China, 2items
OrganizationGrant numberCountry
National Natural Science Foundation of China (NSFC)82003576 China
National Natural Science Foundation of China (NSFC)21877134 China
CitationJournal: Biochem Pharmacol / Year: 2022
Title: Structure-based optimization of Toddacoumalone as highly potent and selective PDE4 inhibitors with anti-inflammatory effects.
Authors: Zhou, F. / Huang, Y. / Liu, L. / Song, Z. / Hou, K.Q. / Yang, Y. / Luo, H.B. / Huang, Y.Y. / Xiong, X.F.
History
DepositionMar 21, 2022Deposition site: PDBJ / Processing site: PDBJ
Revision 1.0Jul 6, 2022Provider: repository / Type: Initial release
Revision 1.1Nov 29, 2023Group: Data collection / Refinement description
Category: chem_comp_atom / chem_comp_bond / pdbx_initial_refinement_model

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

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


Theoretical massNumber of molelcules
Total (without water)116,6378
Polymers115,7192
Non-polymers9186
Water7,512417
1


  • Idetical with deposited unit
  • defined by author&software
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area1950 Å2
ΔGint-103 kcal/mol
Surface area27540 Å2
MethodPISA
Unit cell
Length a, b, c (Å)58.057, 80.416, 162.918
Angle α, β, γ (deg.)90.000, 90.000, 90.000
Int Tables number19
Space group name H-MP212121
Space group name HallP2ac2ab
Symmetry operation#1: x,y,z
#2: x+1/2,-y+1/2,-z
#3: -x,y+1/2,-z+1/2
#4: -x+1/2,-y,z+1/2

-
Components

#1: Protein Isoform 3 of cAMP-specific 3',5'-cyclic phosphodiesterase 4D / DPDE3 / PDE43


Mass: 57859.504 Da / Num. of mol.: 2
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: PDE4D, DPDE3 / Production host: Escherichia coli BL21 (bacteria)
References: UniProt: Q08499, 3',5'-cyclic-AMP phosphodiesterase
#2: Chemical ChemComp-ZN / ZINC ION


Mass: 65.409 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: Zn
#3: Chemical ChemComp-MG / MAGNESIUM ION


Mass: 24.305 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: Mg
#4: Chemical ChemComp-B6V / (2~{R},4~{S})-6-ethyl-2-[(2~{E})-2-hydroxyiminoethyl]-2,8-dimethyl-4-(2-methylprop-1-enyl)-3,4-dihydropyrano[3,2-c][1,8]naphthyridin-5-one


Mass: 369.457 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C21H27N3O3 / Feature type: SUBJECT OF INVESTIGATION
#5: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 417 / 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

Crystal growTemperature: 277 K / Method: vapor diffusion, hanging drop
Details: 0.1 M Hepes (pH 7.4), 0.1 M MgCl2, 15% PEG 3350, 10% isopropanol, 25% ethylene glycol

-
Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: ROTATING ANODE / Type: RIGAKU / Wavelength: 1.5418 Å
DetectorType: RIGAKU HyPix-3000 / Detector: PIXEL / Date: Jan 6, 2022
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1.5418 Å / Relative weight: 1
ReflectionResolution: 2.1→24.34 Å / Num. obs: 45273 / % possible obs: 99.8 % / Redundancy: 4.8 % / Rmerge(I) obs: 0.084 / Net I/σ(I): 14.1
Reflection shellResolution: 2.1→2.18 Å / Redundancy: 3.3 % / Rmerge(I) obs: 0.293 / Mean I/σ(I) obs: 3.4 / Num. unique obs: 4489 / % possible all: 100

-
Processing

Software
NameVersionClassification
PHENIX1.10_2155refinement
CrysalisProdata reduction
CrysalisProdata scaling
PHASERphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 5WQA

5wqa


Resolution: 2.10000900931→24.3365211701 Å / SU ML: 0.212169150848 / Cross valid method: NONE / σ(F): 1.36559810472 / Phase error: 22.7806360388
Stereochemistry target values: GeoStd + Monomer Library + CDL v1.2
RfactorNum. reflection% reflection
Rfree0.243531009297 2226 4.91705506837 %
Rwork0.211212919331 43045 -
obs0.212801294238 45271 99.7905920734 %
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT BULK SOLVENT MODEL
Displacement parametersBiso mean: 24.3573805474 Å2
Refinement stepCycle: LAST / Resolution: 2.10000900931→24.3365211701 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms5230 0 58 417 5705
Refine LS restraints
Refine-IDTypeDev idealNumber
X-RAY DIFFRACTIONf_bond_d0.006650543769865394
X-RAY DIFFRACTIONf_angle_d1.026758170387334
X-RAY DIFFRACTIONf_chiral_restr0.0415689404997842
X-RAY DIFFRACTIONf_plane_restr0.00561835929021938
X-RAY DIFFRACTIONf_dihedral_angle_d15.37329348473244
LS refinement shell
Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkRefine-ID% reflection obs (%)
2.10001-2.14560.3056265552011390.26293660342663X-RAY DIFFRACTION100
2.1456-2.19550.2902416184451480.254394524872644X-RAY DIFFRACTION100
2.1955-2.25040.2997615941491310.2467297910512678X-RAY DIFFRACTION100
2.2504-2.31120.2795027489571390.245147200012656X-RAY DIFFRACTION100
2.3112-2.37910.2711361377481260.2420856467492635X-RAY DIFFRACTION100
2.3791-2.45590.2768770638421180.2256977432762688X-RAY DIFFRACTION100
2.4559-2.54360.2560200565471360.2358180297862695X-RAY DIFFRACTION100
2.5436-2.64530.2863648615371380.2279477037612652X-RAY DIFFRACTION100
2.6453-2.76550.2777293852611540.2245731045942698X-RAY DIFFRACTION100
2.7655-2.91110.2688873797071280.2205930807462680X-RAY DIFFRACTION100
2.9111-3.09310.2420152496091360.2163578531552687X-RAY DIFFRACTION100
3.0931-3.33140.2076786648291510.2095363098122669X-RAY DIFFRACTION100
3.3314-3.66570.2159796806911470.1981490097392716X-RAY DIFFRACTION99.9301919721
3.6657-4.19370.212935457341490.189113649642706X-RAY DIFFRACTION99.9299964998
4.1937-5.27480.2090834759111460.1710537816972769X-RAY DIFFRACTION99.7604380561
5.2748-24.3360.2206188471051400.1844641790682809X-RAY DIFFRACTION97.2946222369

+
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