[English] 日本語
Yorodumi
- PDB-6feb: Crystal structure of human phosphodiesterase 4D2 catalytic domain... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 6feb
TitleCrystal structure of human phosphodiesterase 4D2 catalytic domain with inhibitor NPD-1086
ComponentscAMP-specific 3',5'-cyclic phosphodiesterase 4D
KeywordsHYDROLASE / phosphodiesterase / cAMP hydrolysis / alternative splicing
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 / adrenergic receptor signaling pathway / heterocyclic compound binding / regulation of cell communication by electrical coupling involved in cardiac conduction / cAMP catabolic process / 3',5'-cyclic-nucleotide phosphodiesterase activity / 3',5'-cyclic-GMP phosphodiesterase activity / DARPP-32 events / 3',5'-cyclic-AMP phosphodiesterase activity / positive regulation of heart rate / cAMP-mediated signaling / cAMP binding / regulation of release of sequestered calcium ion into cytosol by sarcoplasmic reticulum / cellular response to cAMP / cellular response to epinephrine stimulus / calcium channel regulator activity / calcium channel complex / positive regulation of interleukin-2 production / regulation of heart rate / Turbulent (oscillatory, disturbed) flow shear stress activates signaling by PIEZO1 and integrins in endothelial cells / positive regulation of type II interferon production / T cell receptor signaling pathway / ATPase binding / scaffold protein binding / G alpha (s) signalling events / nuclear membrane / transmembrane transporter binding / cilium / apical plasma membrane / centrosome / enzyme binding / nucleoplasm / metal ion binding / membrane / plasma membrane / cytosol
Similarity search - Function
Phosphodiesterase 4 upstream conserved regions (UCR) / Phosphodiesterase 4 upstream conserved regions (UCR) / Catalytic domain of cyclic nucleotide phosphodiesterase 4b2b / 3'5'-cyclic nucleotide phosphodiesterase, catalytic domain / 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. ...Phosphodiesterase 4 upstream conserved regions (UCR) / Phosphodiesterase 4 upstream conserved regions (UCR) / Catalytic domain of cyclic nucleotide phosphodiesterase 4b2b / 3'5'-cyclic nucleotide phosphodiesterase, catalytic domain / 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. / Orthogonal Bundle / Mainly Alpha
Similarity search - Domain/homology
Chem-D5Z / 3',5'-cyclic-AMP phosphodiesterase 4D
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 1.93 Å
AuthorsSingh, A.K. / Brown, D.G.
CitationJournal: To be published
Title: hPDE4D2 structure with inhibitor NPD-1086
Authors: Salado, I.G. / Moreno, C. / Sakaine, G. / Singh, A.K. / Blaazer, A.R. / Siderius, M. / Matheeussen, A. / Gul, S. / Maes, L. / Leurs, R. / Brown, D.G. / Augustyns, K.
History
DepositionDec 31, 2017Deposition site: PDBE / Processing site: PDBE
Revision 1.0Apr 10, 2019Provider: repository / Type: Initial release
Revision 1.1Jan 17, 2024Group: Data collection / Database references ...Data collection / Database references / Derived calculations / Refinement description
Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / database_2 / pdbx_initial_refinement_model / pdbx_struct_conn_angle / software / struct_conn
Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession ..._database_2.pdbx_DOI / _database_2.pdbx_database_accession / _pdbx_struct_conn_angle.ptnr1_auth_seq_id / _pdbx_struct_conn_angle.ptnr3_auth_seq_id / _pdbx_struct_conn_angle.value / _software.name / _struct_conn.pdbx_dist_value / _struct_conn.ptnr1_auth_asym_id / _struct_conn.ptnr1_auth_comp_id / _struct_conn.ptnr1_auth_seq_id / _struct_conn.ptnr1_label_asym_id / _struct_conn.ptnr1_label_atom_id / _struct_conn.ptnr1_label_comp_id / _struct_conn.ptnr1_label_seq_id / _struct_conn.ptnr2_auth_asym_id / _struct_conn.ptnr2_auth_comp_id / _struct_conn.ptnr2_auth_seq_id / _struct_conn.ptnr2_label_asym_id / _struct_conn.ptnr2_label_atom_id / _struct_conn.ptnr2_label_comp_id

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

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


Theoretical massNumber of molelcules
Total (without water)86,99030
Polymers83,6162
Non-polymers3,37328
Water5,441302
1
A: cAMP-specific 3',5'-cyclic phosphodiesterase 4D
hetero molecules


Theoretical massNumber of molelcules
Total (without water)43,84417
Polymers41,8081
Non-polymers2,03616
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
2
B: cAMP-specific 3',5'-cyclic phosphodiesterase 4D
hetero molecules


Theoretical massNumber of molelcules
Total (without water)43,14513
Polymers41,8081
Non-polymers1,33712
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Unit cell
Length a, b, c (Å)95.068, 158.233, 111.405
Angle α, β, γ (deg.)90.00, 90.00, 90.00
Int Tables number20
Space group name H-MC2221

-
Components

-
Protein , 1 types, 2 molecules AB

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


Mass: 41808.242 Da / Num. of mol.: 2
Source method: isolated from a genetically manipulated source
Details: residues 381-740 / Source: (gene. exp.) Homo sapiens (human) / Gene: PDE4D, DPDE3 / Plasmid: pET15b / Production host: Escherichia coli BL21(DE3) (bacteria) / Variant (production host): codon plus
References: UniProt: Q08499, 3',5'-cyclic-AMP phosphodiesterase

-
Non-polymers , 6 types, 330 molecules

#2: Chemical
ChemComp-EDO / 1,2-ETHANEDIOL / ETHYLENE GLYCOL


Mass: 62.068 Da / Num. of mol.: 19 / Source method: obtained synthetically / Formula: C2H6O2
#3: Chemical ChemComp-D5Z / (4aS,8aR)-2-[1-(2-aminoquinazolin-4-yl)piperidin-4-yl]-4-(3,4-dimethoxyphenyl)-1,2,4a,5,8,8a-hexahydrophthalazin-1-one


Mass: 512.603 Da / Num. of mol.: 3 / Source method: obtained synthetically / Formula: C29H32N6O3 / Feature type: SUBJECT OF INVESTIGATION
#4: Chemical ChemComp-MG / MAGNESIUM ION


Mass: 24.305 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: Mg
#5: Chemical ChemComp-ZN / ZINC ION


Mass: 65.409 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: Zn
#6: Chemical ChemComp-EPE / 4-(2-HYDROXYETHYL)-1-PIPERAZINE ETHANESULFONIC ACID / HEPES


Mass: 238.305 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C8H18N2O4S / Comment: pH buffer*YM
#7: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 302 / Source method: isolated from a natural source / Formula: H2O

-
Experimental details

-
Experiment

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

-
Sample preparation

CrystalDensity Matthews: 2.51 Å3/Da / Density % sol: 50.99 %
Crystal growTemperature: 293 K / Method: vapor diffusion, hanging drop / pH: 7.5 / Details: 24% PEG 3350, 30% Ethylene Glycol, 0.1 M HEPES

-
Data collection

DiffractionMean temperature: 100 K
Diffraction sourceSource: SYNCHROTRON / Site: Diamond / Beamline: I03 / Wavelength: 0.97622 Å
DetectorType: DECTRIS PILATUS3 6M / Detector: PIXEL / Date: Sep 12, 2016 / Details: CRL
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.97622 Å / Relative weight: 1
ReflectionResolution: 1.928→81.491 Å / Num. obs: 62982 / % possible obs: 99.1 % / Redundancy: 6.6 % / CC1/2: 0.999 / Rmerge(I) obs: 0.061 / Rpim(I) all: 0.026 / Rrim(I) all: 0.066 / Net I/σ(I): 19.3
Reflection shellResolution: 1.928→1.961 Å / Redundancy: 6.8 % / Rmerge(I) obs: 0.844 / Mean I/σ(I) obs: 2.2 / Num. unique obs: 3129 / CC1/2: 0.723 / Rpim(I) all: 0.345 / Rrim(I) all: 0.913 / % possible all: 99.5

-
Processing

Software
NameVersionClassification
REFMAC5.8.0189refinement
XDSdata reduction
autoPROCdata scaling
PHASERphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 3SL3

3sl3


Resolution: 1.93→81.49 Å / Cor.coef. Fo:Fc: 0.971 / Cor.coef. Fo:Fc free: 0.958 / SU B: 3.055 / SU ML: 0.086 / Cross valid method: THROUGHOUT / ESU R: 0.125 / ESU R Free: 0.12
Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS U values refined individually
RfactorNum. reflection% reflectionSelection details
Rfree0.19608 3200 5.1 %RANDOM
Rwork0.1599 ---
obs0.16173 59752 99.09 %-
Solvent computationIon probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.2 Å
Displacement parametersBiso mean: 39.066 Å2
Baniso -1Baniso -2Baniso -3
1--0.41 Å20 Å20 Å2
2--0.89 Å20 Å2
3----0.48 Å2
Refinement stepCycle: 1 / Resolution: 1.93→81.49 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms5246 0 224 302 5772
Refine LS restraints
Refine-IDTypeDev idealDev ideal targetNumber
X-RAY DIFFRACTIONr_bond_refined_d0.0140.0195576
X-RAY DIFFRACTIONr_bond_other_d0.0020.025123
X-RAY DIFFRACTIONr_angle_refined_deg1.6251.9557544
X-RAY DIFFRACTIONr_angle_other_deg1.0372.97511896
X-RAY DIFFRACTIONr_dihedral_angle_1_deg5.665646
X-RAY DIFFRACTIONr_dihedral_angle_2_deg35.03324.643280
X-RAY DIFFRACTIONr_dihedral_angle_3_deg15.48515954
X-RAY DIFFRACTIONr_dihedral_angle_4_deg16.3541526
X-RAY DIFFRACTIONr_chiral_restr0.1010.2854
X-RAY DIFFRACTIONr_gen_planes_refined0.0080.026052
X-RAY DIFFRACTIONr_gen_planes_other0.0010.021056
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_it3.0073.6532590
X-RAY DIFFRACTIONr_mcbond_other2.9983.6512589
X-RAY DIFFRACTIONr_mcangle_it4.2845.463234
X-RAY DIFFRACTIONr_mcangle_other4.2845.4613235
X-RAY DIFFRACTIONr_scbond_it3.9724.1632986
X-RAY DIFFRACTIONr_scbond_other3.9714.1632986
X-RAY DIFFRACTIONr_scangle_it
X-RAY DIFFRACTIONr_scangle_other6.1646.044311
X-RAY DIFFRACTIONr_long_range_B_refined8.49144.9016676
X-RAY DIFFRACTIONr_long_range_B_other8.49144.916676
X-RAY DIFFRACTIONr_rigid_bond_restr
X-RAY DIFFRACTIONr_sphericity_free
X-RAY DIFFRACTIONr_sphericity_bonded
LS refinement shellResolution: 1.928→1.978 Å / Total num. of bins used: 20
RfactorNum. reflection% reflection
Rfree0.301 232 -
Rwork0.263 4401 -
obs--99.91 %

+
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