[English] 日本語
Yorodumi
- PDB-3ly2: Catalytic Domain of Human Phosphodiesterase 4B in Complex with A ... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 3ly2
TitleCatalytic Domain of Human Phosphodiesterase 4B in Complex with A Coumarin-Based Inhibitor
ComponentscAMP-specific 3',5'-cyclic phosphodiesterase 4B
KeywordsHYDROLASE/HYDROLASE INHIBITOR / PDE4B / COUMARIN / INHIBITOR / HYDROLASE / Metal-binding / HYDROLASE-HYDROLASE INHIBITOR complex
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 / regulation of cardiac muscle cell contraction / gamma-tubulin binding / regulation of calcium ion transmembrane transport via high voltage-gated calcium channel / leukocyte migration / voltage-gated calcium channel complex ...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 / regulation of cardiac muscle cell contraction / gamma-tubulin binding / regulation of calcium ion transmembrane transport via high voltage-gated calcium channel / leukocyte migration / voltage-gated calcium channel complex / cAMP catabolic process / calcium channel regulator activity / excitatory synapse / 3',5'-cyclic-AMP phosphodiesterase activity / DARPP-32 events / cAMP binding / cellular response to epinephrine stimulus / positive regulation of interleukin-2 production / 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 / signal transduction / metal ion binding / nucleus / 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. / Metal dependent phosphohydrolases with conserved 'HD' motif. / HD/PDEase domain / Orthogonal Bundle / Mainly Alpha
Similarity search - Domain/homology
Chem-Z72 / 3',5'-cyclic-AMP phosphodiesterase 4B
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.6 Å
AuthorsShiau, A.K. / Coyle, A.R. / Hsien, J.H. / Staszewski, L.M.
CitationJournal: Bioorg.Med.Chem.Lett. / Year: 2010
Title: Water-soluble PDE4 inhibitors for the treatment of dry eye.
Authors: Govek, S.P. / Oshiro, G. / Anzola, J.V. / Beauregard, C. / Chen, J. / Coyle, A.R. / Gamache, D.A. / Hellberg, M.R. / Hsien, J.N. / Lerch, J.M. / Liao, J.C. / Malecha, J.W. / Staszewski, L.M. ...Authors: Govek, S.P. / Oshiro, G. / Anzola, J.V. / Beauregard, C. / Chen, J. / Coyle, A.R. / Gamache, D.A. / Hellberg, M.R. / Hsien, J.N. / Lerch, J.M. / Liao, J.C. / Malecha, J.W. / Staszewski, L.M. / Thomas, D.J. / Yanni, J.M. / Noble, S.A. / Shiau, A.K.
History
DepositionFeb 26, 2010Deposition site: RCSB / Processing site: RCSB
Revision 1.0Apr 28, 2010Provider: repository / Type: Initial release
Revision 1.1Jul 13, 2011Group: Version format compliance
Revision 1.2Sep 6, 2023Group: 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 / struct_conn / struct_ref_seq_dif / struct_site
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_asym_id / _pdbx_struct_conn_angle.ptnr1_auth_comp_id / _pdbx_struct_conn_angle.ptnr1_auth_seq_id / _pdbx_struct_conn_angle.ptnr1_label_asym_id / _pdbx_struct_conn_angle.ptnr1_label_atom_id / _pdbx_struct_conn_angle.ptnr1_label_comp_id / _pdbx_struct_conn_angle.ptnr1_label_seq_id / _pdbx_struct_conn_angle.ptnr2_auth_asym_id / _pdbx_struct_conn_angle.ptnr2_auth_comp_id / _pdbx_struct_conn_angle.ptnr2_auth_seq_id / _pdbx_struct_conn_angle.ptnr2_label_asym_id / _pdbx_struct_conn_angle.ptnr2_label_atom_id / _pdbx_struct_conn_angle.ptnr2_label_comp_id / _pdbx_struct_conn_angle.ptnr3_auth_asym_id / _pdbx_struct_conn_angle.ptnr3_auth_comp_id / _pdbx_struct_conn_angle.ptnr3_auth_seq_id / _pdbx_struct_conn_angle.ptnr3_label_asym_id / _pdbx_struct_conn_angle.ptnr3_label_atom_id / _pdbx_struct_conn_angle.ptnr3_label_comp_id / _pdbx_struct_conn_angle.ptnr3_label_seq_id / _pdbx_struct_conn_angle.value / _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 / _struct_ref_seq_dif.details / _struct_site.pdbx_auth_asym_id / _struct_site.pdbx_auth_comp_id / _struct_site.pdbx_auth_seq_id

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: cAMP-specific 3',5'-cyclic phosphodiesterase 4B
B: cAMP-specific 3',5'-cyclic phosphodiesterase 4B
C: cAMP-specific 3',5'-cyclic phosphodiesterase 4B
D: cAMP-specific 3',5'-cyclic phosphodiesterase 4B
E: cAMP-specific 3',5'-cyclic phosphodiesterase 4B
F: cAMP-specific 3',5'-cyclic phosphodiesterase 4B
G: cAMP-specific 3',5'-cyclic phosphodiesterase 4B
H: cAMP-specific 3',5'-cyclic phosphodiesterase 4B
hetero molecules


Theoretical massNumber of molelcules
Total (without water)332,44334
Polymers328,1638
Non-polymers4,28026
Water8,899494
1
A: cAMP-specific 3',5'-cyclic phosphodiesterase 4B
hetero molecules


Theoretical massNumber of molelcules
Total (without water)41,6275
Polymers41,0201
Non-polymers6074
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
MethodPISA
2
B: cAMP-specific 3',5'-cyclic phosphodiesterase 4B
hetero molecules


Theoretical massNumber of molelcules
Total (without water)41,6275
Polymers41,0201
Non-polymers6074
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
MethodPISA
3
C: cAMP-specific 3',5'-cyclic phosphodiesterase 4B
hetero molecules


Theoretical massNumber of molelcules
Total (without water)41,5314
Polymers41,0201
Non-polymers5113
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
MethodPISA
4
D: cAMP-specific 3',5'-cyclic phosphodiesterase 4B
hetero molecules


Theoretical massNumber of molelcules
Total (without water)41,5314
Polymers41,0201
Non-polymers5113
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
MethodPISA
5
E: cAMP-specific 3',5'-cyclic phosphodiesterase 4B
hetero molecules


Theoretical massNumber of molelcules
Total (without water)41,5314
Polymers41,0201
Non-polymers5113
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
MethodPISA
6
F: cAMP-specific 3',5'-cyclic phosphodiesterase 4B
hetero molecules


Theoretical massNumber of molelcules
Total (without water)41,5314
Polymers41,0201
Non-polymers5113
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
MethodPISA
7
G: cAMP-specific 3',5'-cyclic phosphodiesterase 4B
hetero molecules


Theoretical massNumber of molelcules
Total (without water)41,5314
Polymers41,0201
Non-polymers5113
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
MethodPISA
8
H: cAMP-specific 3',5'-cyclic phosphodiesterase 4B
hetero molecules


Theoretical massNumber of molelcules
Total (without water)41,5314
Polymers41,0201
Non-polymers5113
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
MethodPISA
Unit cell
Length a, b, c (Å)214.796, 233.964, 165.258
Angle α, β, γ (deg.)90.00, 90.00, 90.00
Int Tables number20
Space group name H-MC2221

-
Components

-
Protein , 1 types, 8 molecules ABCDEFGH

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


Mass: 41020.348 Da / Num. of mol.: 8 / Fragment: CATALYTIC DOMAIN, residues 324-659
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: DPDE4, PDE4B / Plasmid: PET28A / Production host: Escherichia coli (E. coli) / Strain (production host): BL21(DE3)
References: UniProt: Q07343, 3',5'-cyclic-nucleotide phosphodiesterase

-
Non-polymers , 5 types, 520 molecules

#2: Chemical
ChemComp-Z72 / 8-(cyclopentyloxy)-4-[(3,5-dichloropyridin-4-yl)amino]-7-methoxy-2H-chromen-2-one


Mass: 421.274 Da / Num. of mol.: 8 / Source method: obtained synthetically / Formula: C20H18Cl2N2O4
#3: Chemical
ChemComp-ZN / ZINC ION


Mass: 65.409 Da / Num. of mol.: 8 / Source method: obtained synthetically / Formula: Zn
#4: Chemical
ChemComp-MG / MAGNESIUM ION


Mass: 24.305 Da / Num. of mol.: 8 / Source method: obtained synthetically / Formula: Mg
#5: Chemical ChemComp-SO4 / SULFATE ION / Sulfate


Mass: 96.063 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: SO4
#6: Water ChemComp-HOH / water / Water


Mass: 18.015 Da / Num. of mol.: 494 / 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: 3.16 Å3/Da / Density % sol: 61.12 %
Crystal growTemperature: 277 K / Method: vapor diffusion, hanging drop / pH: 6
Details: 1.8-2.0M AMMONIUM SULFATE, 1-2% PEG 400, 0.1M SODIUM CACODYLATE, pH 6.0, VAPOR DIFFUSION, HANGING DROP, temperature 277K

-
Data collection

DiffractionMean temperature: 100 K
Diffraction sourceSource: SYNCHROTRON / Site: ALS / Beamline: 5.0.3 / Wavelength: 1 Å
DetectorType: ADSC QUANTUM 315 / Detector: CCD / Date: Sep 30, 2006
RadiationMonochromator: SI(220) ASYMMETRIC CURVED CRYSTAL / Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1 Å / Relative weight: 1
ReflectionResolution: 2.6→49.84 Å / Num. all: 127998 / Num. obs: 127998 / % possible obs: 100 % / Observed criterion σ(I): -3 / Redundancy: 7.5 % / Biso Wilson estimate: 47.6 Å2 / Rsym value: 0.121 / Net I/σ(I): 18.8
Reflection shellResolution: 2.6→2.64 Å / Redundancy: 7.6 % / Mean I/σ(I) obs: 2.5 / Num. unique all: 6371 / Rsym value: 0.781 / % possible all: 100

-
Processing

Software
NameClassification
Blu-Icedata collection
PHASERphasing
CNXrefinement
DENZOdata reduction
SCALEPACKdata scaling
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: PDB ENTRY 1XM4

1xm4


Resolution: 2.6→49.84 Å / Isotropic thermal model: RESTRAINED / Cross valid method: THROUGHOUT / σ(F): 0 / Stereochemistry target values: Engh & Huber
Details: ADDITIONAL DENSITY, LIKELY CORRESPONDING TO PARTIAL OCCUPANCY OF A CACODYLATE ION (SEE PDB 1F0J), IS EVIDENT NEAR THE BINUCLEAR METAL CLUSTER. NO ATTEMPT WAS MADE TO MODEL THIS DENSITY
RfactorNum. reflection% reflectionSelection details
Rfree0.233 6404 -RANDOM
Rwork0.205 ---
all-127269 --
obs-127269 100 %-
Displacement parametersBiso mean: 38.7 Å2
Baniso -1Baniso -2Baniso -3
1--3.25 Å24.56 Å2-1.31 Å2
2--0 Å20 Å2
3---0 Å2
Refine analyze
FreeObs
Luzzati coordinate error0.35 Å0.3 Å
Luzzati d res low-5 Å
Luzzati sigma a0.4 Å0.34 Å
Refinement stepCycle: LAST / Resolution: 2.6→49.84 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms21521 0 250 494 22265
Refine LS restraints
Refine-IDTypeDev ideal
X-RAY DIFFRACTIONc_bond_d0.008
X-RAY DIFFRACTIONc_angle_deg1.2
X-RAY DIFFRACTIONc_dihedral_angle_deg19.4
X-RAY DIFFRACTIONc_improper_angle_deg0.76
LS refinement shellResolution: 2.6→2.64 Å / Rfactor Rfree error: 0.019
RfactorNum. reflection% reflection
Rfree0.328 310 -
Rwork0.288 --
obs-6277 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