[English] 日本語
Yorodumi
- PDB-5u7j: PDE2 catalytic domain complexed with inhibitors -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 5u7j
TitlePDE2 catalytic domain complexed with inhibitors
ComponentscGMP-dependent 3',5'-cyclic phosphodiesterase
KeywordsHydrolase/Hydrolase Inhibitor / PDE2 / SBDD / inhibitor / phosphodiesterase / Hydrolase-Hydrolase Inhibitor complex
Function / homology
Function and homology information


: / cellular response to 2,3,7,8-tetrachlorodibenzodioxine / cellular response to macrophage colony-stimulating factor stimulus / cellular response to cGMP / negative regulation of adenylate cyclase-activating G protein-coupled receptor signaling pathway / heart valve development / positive regulation of vascular permeability / cellular response to granulocyte macrophage colony-stimulating factor stimulus / negative regulation of vascular permeability / establishment of endothelial barrier ...: / cellular response to 2,3,7,8-tetrachlorodibenzodioxine / cellular response to macrophage colony-stimulating factor stimulus / cellular response to cGMP / negative regulation of adenylate cyclase-activating G protein-coupled receptor signaling pathway / heart valve development / positive regulation of vascular permeability / cellular response to granulocyte macrophage colony-stimulating factor stimulus / negative regulation of vascular permeability / establishment of endothelial barrier / regulation of mitochondrion organization / : / 3',5'-cGMP-stimulated cyclic-nucleotide phosphodiesterase activity / aorta development / ventricular septum development / 3',5'-cyclic-nucleotide phosphodiesterase / negative regulation of receptor guanylyl cyclase signaling pathway / cGMP catabolic process / cGMP effects / phosphate ion binding / TPR domain binding / cGMP binding / monocyte differentiation / 3',5'-cyclic-GMP phosphodiesterase activity / 3',5'-cyclic-AMP phosphodiesterase activity / cellular response to transforming growth factor beta stimulus / : / cAMP binding / synaptic membrane / cellular response to cAMP / cellular response to mechanical stimulus / adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway / cellular response to xenobiotic stimulus / positive regulation of inflammatory response / presynaptic membrane / G alpha (s) signalling events / mitochondrial outer membrane / mitochondrial inner membrane / mitochondrial matrix / positive regulation of gene expression / perinuclear region of cytoplasm / magnesium ion binding / endoplasmic reticulum / negative regulation of transcription by RNA polymerase II / Golgi apparatus / protein homodimerization activity / zinc ion binding / identical protein binding / nucleus / plasma membrane / cytosol / cytoplasm
Similarity search - Function
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. / GAF domain ...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. / GAF domain / Domain present in phytochromes and cGMP-specific phosphodiesterases. / GAF domain / Metal dependent phosphohydrolases with conserved 'HD' motif. / HD/PDEase domain / GAF-like domain superfamily / Orthogonal Bundle / Mainly Alpha
Similarity search - Domain/homology
Chem-7XV / cGMP-dependent 3',5'-cyclic phosphodiesterase
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 1.9 Å
AuthorsPandit, J. / Parris, K.
CitationJournal: J. Med. Chem. / Year: 2017
Title: Application of Structure-Based Design and Parallel Chemistry to Identify a Potent, Selective, and Brain Penetrant Phosphodiesterase 2A Inhibitor.
Authors: Helal, C.J. / Arnold, E.P. / Boyden, T.L. / Chang, C. / Chappie, T.A. / Fennell, K.F. / Forman, M.D. / Hajos, M. / Harms, J.F. / Hoffman, W.E. / Humphrey, J.M. / Kang, Z. / Kleiman, R.J. / ...Authors: Helal, C.J. / Arnold, E.P. / Boyden, T.L. / Chang, C. / Chappie, T.A. / Fennell, K.F. / Forman, M.D. / Hajos, M. / Harms, J.F. / Hoffman, W.E. / Humphrey, J.M. / Kang, Z. / Kleiman, R.J. / Kormos, B.L. / Lee, C.W. / Lu, J. / Maklad, N. / McDowell, L. / Mente, S. / O'Connor, R.E. / Pandit, J. / Piotrowski, M. / Schmidt, A.W. / Schmidt, C.J. / Ueno, H. / Verhoest, P.R. / Yang, E.X.
History
DepositionDec 12, 2016Deposition site: RCSB / Processing site: RCSB
Revision 1.0Jun 28, 2017Provider: repository / Type: Initial release
Revision 1.1Jul 26, 2017Group: Database references / Category: citation / citation_author
Item: _citation.journal_volume / _citation.page_first ..._citation.journal_volume / _citation.page_first / _citation.page_last / _citation_author.name
Revision 1.2Nov 22, 2017Group: Refinement description / Category: software / Item: _software.name
Revision 1.3Oct 4, 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
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 / _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: cGMP-dependent 3',5'-cyclic phosphodiesterase
B: cGMP-dependent 3',5'-cyclic phosphodiesterase
C: cGMP-dependent 3',5'-cyclic phosphodiesterase
D: cGMP-dependent 3',5'-cyclic phosphodiesterase
hetero molecules


Theoretical massNumber of molelcules
Total (without water)162,56516
Polymers160,9004
Non-polymers1,66412
Water22,4111244
1
A: cGMP-dependent 3',5'-cyclic phosphodiesterase
hetero molecules


Theoretical massNumber of molelcules
Total (without water)40,6414
Polymers40,2251
Non-polymers4163
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
MethodPISA
2
B: cGMP-dependent 3',5'-cyclic phosphodiesterase
hetero molecules


Theoretical massNumber of molelcules
Total (without water)40,6414
Polymers40,2251
Non-polymers4163
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
MethodPISA
3
C: cGMP-dependent 3',5'-cyclic phosphodiesterase
hetero molecules


Theoretical massNumber of molelcules
Total (without water)40,6414
Polymers40,2251
Non-polymers4163
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
MethodPISA
4
D: cGMP-dependent 3',5'-cyclic phosphodiesterase
hetero molecules


Theoretical massNumber of molelcules
Total (without water)40,6414
Polymers40,2251
Non-polymers4163
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
MethodPISA
Unit cell
Length a, b, c (Å)55.866, 74.035, 92.411
Angle α, β, γ (deg.)109.660, 91.430, 90.920
Int Tables number1
Space group name H-MP1

-
Components

#1: Protein
cGMP-dependent 3',5'-cyclic phosphodiesterase / Cyclic GMP-stimulated phosphodiesterase / cGSPDE


Mass: 40225.102 Da / Num. of mol.: 4 / Fragment: Catalytic domain of PDE2, UNP residues 323-663
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: PDE2A / Production host: Spodoptera frugiperda (fall armyworm) / Strain (production host): Sf21
References: UniProt: O00408, 3',5'-cyclic-nucleotide phosphodiesterase
#2: Chemical
ChemComp-7XV / 5-[2-(2-methoxyphenyl)ethoxy]-3-(2-methylpropyl)[1,2,4]triazolo[4,3-a]pyrazine


Mass: 326.393 Da / Num. of mol.: 4 / Source method: obtained synthetically / Formula: C18H22N4O2
#3: Chemical
ChemComp-ZN / ZINC ION


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


Mass: 24.305 Da / Num. of mol.: 4 / Source method: obtained synthetically / Formula: Mg
#5: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 1244 / 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: 2.24 Å3/Da / Density % sol: 44.98 %
Crystal growTemperature: 294 K / Method: vapor diffusion, hanging drop / Details: 25% PEG 3350, 0.1 M Tris, pH 8.5, and 0.2 M MgCl2

-
Data collection

DiffractionMean temperature: 100 K
Diffraction sourceSource: SYNCHROTRON / Site: APS / Beamline: 17-ID / Wavelength: 1 Å
DetectorType: ADSC QUANTUM 210 / Detector: CCD / Date: Apr 6, 2006
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1 Å / Relative weight: 1
ReflectionResolution: 1.89→50 Å / Num. obs: 106624 / % possible obs: 95.9 % / Redundancy: 2 % / Biso Wilson estimate: 23.54 Å2 / Rmerge(I) obs: 0.061 / Χ2: 1.401 / Net I/σ(I): 9.4 / Num. measured all: 210202
Reflection shell
Resolution (Å)Redundancy (%)Rmerge(I) obsNum. unique allΧ2Diffraction-ID% possible all
1.89-1.961.90.44399651.653189.6
1.96-2.0420.307107041.024196.6
2.04-2.1320.218106121.415195.2
2.13-2.2420.173106651.407195.9
2.24-2.3820.128106291.445195.9
2.38-2.5720.084108251.182197.4
2.57-2.8220.066108641.28197.8
2.82-3.2320.048109041.445197.9
3.23-4.0720.036107461.741196.8
4.07-5020.027107101.458196.4

-
Processing

Software
NameVersionClassification
HKL-2000data collection
SCALEPACKdata scaling
BUSTER2.11.5refinement
PDB_EXTRACT3.22data extraction
HKL-2000data reduction
DENZOdata reduction
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 3ITU

3itu


Resolution: 1.9→44.18 Å / Cor.coef. Fo:Fc: 0.9411 / Cor.coef. Fo:Fc free: 0.9223 / SU R Cruickshank DPI: 0.177 / Cross valid method: THROUGHOUT / σ(F): 0 / SU R Blow DPI: 0.183 / SU Rfree Blow DPI: 0.15 / SU Rfree Cruickshank DPI: 0.148
RfactorNum. reflection% reflectionSelection details
Rfree0.2246 5220 4.98 %RANDOM
Rwork0.1943 ---
obs0.1958 104828 95.46 %-
Displacement parametersBiso max: 117.87 Å2 / Biso mean: 30.15 Å2 / Biso min: 8.2 Å2
Baniso -1Baniso -2Baniso -3
1-4.1068 Å20.4159 Å2-0.2522 Å2
2---3.1972 Å2-0.839 Å2
3----0.9097 Å2
Refine analyzeLuzzati coordinate error obs: 0.287 Å
Refinement stepCycle: final / Resolution: 1.9→44.18 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms10870 0 192 1244 12306
Biso mean--33.94 37.46 -
Num. residues----1328
Refine LS restraints
Refine-IDTypeNumberRestraint functionWeightDev ideal
X-RAY DIFFRACTIONt_dihedral_angle_d4096SINUSOIDAL2
X-RAY DIFFRACTIONt_trig_c_planes275HARMONIC2
X-RAY DIFFRACTIONt_gen_planes1766HARMONIC5
X-RAY DIFFRACTIONt_it11519HARMONIC20
X-RAY DIFFRACTIONt_nbd1SEMIHARMONIC5
X-RAY DIFFRACTIONt_improper_torsion
X-RAY DIFFRACTIONt_pseud_angle
X-RAY DIFFRACTIONt_chiral_improper_torsion1457SEMIHARMONIC5
X-RAY DIFFRACTIONt_sum_occupancies
X-RAY DIFFRACTIONt_utility_distance
X-RAY DIFFRACTIONt_utility_angle
X-RAY DIFFRACTIONt_utility_torsion
X-RAY DIFFRACTIONt_ideal_dist_contact14758SEMIHARMONIC4
X-RAY DIFFRACTIONt_bond_d11519HARMONIC20.009
X-RAY DIFFRACTIONt_angle_deg15642HARMONIC20.91
X-RAY DIFFRACTIONt_omega_torsion2.71
X-RAY DIFFRACTIONt_other_torsion17.46
LS refinement shellResolution: 1.9→1.95 Å / Rfactor Rfree error: 0 / Total num. of bins used: 20
RfactorNum. reflection% reflection
Rfree0.4406 338 5.1 %
Rwork0.4366 6289 -
all0.4368 6627 -
obs--95.46 %
Refinement TLS params.

Method: refined / Refine-ID: X-RAY DIFFRACTION

IDL11 (°2)L12 (°2)L13 (°2)L22 (°2)L23 (°2)L33 (°2)S11 (Å °)S12 (Å °)S13 (Å °)S21 (Å °)S22 (Å °)S23 (Å °)S31 (Å °)S32 (Å °)S33 (Å °)T11 (Å2)T12 (Å2)T13 (Å2)T22 (Å2)T23 (Å2)T33 (Å2)Origin x (Å)Origin y (Å)Origin z (Å)
11.2870.190.24920.81140.11920.90980.0307-0.21050.08750.051-0.03960.0188-0.0554-0.01680.0089-0.0214-0.0178-0.03940.0059-0.0403-0.04290.741-0.6010.646
21.13720.05960.06011.0070.02531.14020.03240.1087-0.0235-0.04060.03020.03060.0154-0.0129-0.0626-0.0170.0103-0.0542-0.0466-0.0344-0.024618.538-3.113-38.897
31.61020.0952-0.37360.7851-0.09531.78120.06910.0914-0.0878-0.09290.0093-0.11950.00010.1368-0.0784-0.07890.0027-0.034-0.0501-0.0939-0.018744.816-37.309-37.98
41.0931-0.15030.04080.74390.2260.85070.0135-0.1407-0.0930.0799-0.01520.05480.031-0.05680.0017-0.0366-0.018-0.05510.00910.00390.002428.389-33.6272.905
50.18010.3448-0.1552-0.24740.1741.0888-0.00680.03010.0977-0.04360.0111-0.1075-0.0442-0.0963-0.00430.0333-0.0311-0.0916-0.03180.02160.116323.1-13.017-18.469
Refinement TLS group
IDRefine-IDRefine TLS-IDSelection detailsAuth asym-IDAuth seq-ID
1X-RAY DIFFRACTION1{ A|579 - A|916 }A579 - 916
2X-RAY DIFFRACTION2{ B|580 - B|915 }B580 - 915
3X-RAY DIFFRACTION3{ C|590 - C|916 }C590 - 916
4X-RAY DIFFRACTION4{ D|590 - D|916 }D590 - 916
5X-RAY DIFFRACTION5{ A|1001 - A|1001 C|1001 - C|1001 B|1001 - B|1001 D|1001 - D|1001 }A1001
6X-RAY DIFFRACTION5{ A|1001 - A|1001 C|1001 - C|1001 B|1001 - B|1001 D|1001 - D|1001 }C1001
7X-RAY DIFFRACTION5{ A|1001 - A|1001 C|1001 - C|1001 B|1001 - B|1001 D|1001 - D|1001 }B1001
8X-RAY DIFFRACTION5{ A|1001 - A|1001 C|1001 - C|1001 B|1001 - B|1001 D|1001 - D|1001 }D1001

+
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