[English] 日本語
Yorodumi
- PDB-3qpn: Structure of PDE10-inhibitor complex -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 3qpn
TitleStructure of PDE10-inhibitor complex
ComponentscAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A
KeywordsHYDROLASE/HYDROLASE INHIBITOR / Phosphodiesterase Inhibitors / Structure-based drug design / HYDROLASE-HYDROLASE INHIBITOR complex
Function / homology
Function and homology information


regulation of adenylate cyclase-activating G protein-coupled receptor signaling pathway / cyclic-nucleotide phosphodiesterase activity / cGMP effects / G alpha (s) signalling events / regulation of protein kinase A signaling / negative regulation of cAMP-mediated signaling / cGMP-stimulated cyclic-nucleotide phosphodiesterase activity / 3',5'-cyclic-nucleotide phosphodiesterase / negative regulation of cGMP-mediated signaling / cGMP catabolic process ...regulation of adenylate cyclase-activating G protein-coupled receptor signaling pathway / cyclic-nucleotide phosphodiesterase activity / cGMP effects / G alpha (s) signalling events / regulation of protein kinase A signaling / negative regulation of cAMP-mediated signaling / cGMP-stimulated cyclic-nucleotide phosphodiesterase activity / 3',5'-cyclic-nucleotide phosphodiesterase / negative regulation of cGMP-mediated signaling / cGMP catabolic process / cAMP catabolic process / 3',5'-cyclic-GMP phosphodiesterase activity / cGMP binding / 3',5'-cyclic-nucleotide phosphodiesterase activity / 3',5'-cyclic-AMP phosphodiesterase activity / cAMP binding / perikaryon / neuronal cell body / signal transduction / metal ion binding / cytosol
Similarity search - Function
Catalytic domain of cyclic nucleotide phosphodiesterase 4b2b / 3'5'-cyclic nucleotide phosphodiesterase, catalytic domain / GAF domain / 3'5'-cyclic nucleotide phosphodiesterase / Domain present in phytochromes and cGMP-specific phosphodiesterases. / 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. ...Catalytic domain of cyclic nucleotide phosphodiesterase 4b2b / 3'5'-cyclic nucleotide phosphodiesterase, catalytic domain / GAF domain / 3'5'-cyclic nucleotide phosphodiesterase / Domain present in phytochromes and cGMP-specific phosphodiesterases. / 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 / GAF-like domain superfamily / Metal dependent phosphohydrolases with conserved 'HD' motif. / HD/PDEase domain / Orthogonal Bundle / Mainly Alpha
Similarity search - Domain/homology
6-methoxy-7-[2-(quinolin-2-yl)ethoxy]quinazoline / cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A
Similarity search - Component
Biological speciesRattus norvegicus (Norway rat)
MethodX-RAY DIFFRACTION / FOURIER SYNTHESIS / Resolution: 2 Å
AuthorsPandit, J. / Marr, E.S.
CitationJournal: J.Med.Chem. / Year: 2011
Title: Use of Structure-Based Design to Discover a Potent, Selective, In Vivo Active Phosphodiesterase 10A Inhibitor Lead Series for the Treatment of Schizophrenia.
Authors: Helal, C.J. / Kang, Z. / Hou, X. / Pandit, J. / Chappie, T.A. / Humphrey, J.M. / Marr, E.S. / Fennell, K.F. / Chenard, L.K. / Fox, C. / Schmidt, C.J. / Williams, R.D. / Chapin, D.S. / ...Authors: Helal, C.J. / Kang, Z. / Hou, X. / Pandit, J. / Chappie, T.A. / Humphrey, J.M. / Marr, E.S. / Fennell, K.F. / Chenard, L.K. / Fox, C. / Schmidt, C.J. / Williams, R.D. / Chapin, D.S. / Siuciak, J. / Lebel, L. / Menniti, F. / Cianfrogna, J. / Fonseca, K.R. / Nelson, F.R. / O'Connor, R. / Macdougall, M. / McDowell, L. / Liras, S.
History
DepositionFeb 14, 2011Deposition site: RCSB / Processing site: RCSB
Revision 1.0Jun 15, 2011Provider: repository / Type: Initial release
Revision 1.1Jul 13, 2011Group: Version format compliance
Revision 1.2Jul 20, 2011Group: Database references
Revision 1.3Feb 21, 2024Group: Data collection / Database references / Derived calculations
Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / database_2 / 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_comp_id / _pdbx_struct_conn_angle.ptnr1_auth_seq_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.ptnr3_auth_comp_id / _pdbx_struct_conn_angle.ptnr3_auth_seq_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_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_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_conn.ptnr2_label_seq_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 and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A
hetero molecules


Theoretical massNumber of molelcules
Total (without water)42,1795
Polymers41,6621
Non-polymers5174
Water1,38777
1


  • Idetical with deposited unit
  • defined by author
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Unit cell
Length a, b, c (Å)120.672, 120.672, 82.647
Angle α, β, γ (deg.)90.000, 90.000, 120.000
Int Tables number146
Space group name H-MH3

-
Components

-
Protein , 1 types, 1 molecules A

#1: Protein cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A


Mass: 41661.715 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Rattus norvegicus (Norway rat) / Gene: Pde10a / Production host: Spodoptera frugiperda (fall armyworm)
References: UniProt: Q9QYJ6, 3',5'-cyclic-nucleotide phosphodiesterase, 3',5'-cyclic-GMP phosphodiesterase

-
Non-polymers , 5 types, 81 molecules

#2: Chemical ChemComp-SO4 / SULFATE ION / Sulfate


Mass: 96.063 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: SO4
#3: Chemical ChemComp-ZN / ZINC ION


Mass: 65.409 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: Zn
#4: Chemical ChemComp-MG / MAGNESIUM ION


Mass: 24.305 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: Mg
#5: Chemical ChemComp-PFK / 6-methoxy-7-[2-(quinolin-2-yl)ethoxy]quinazoline


Mass: 331.368 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C20H17N3O2
#6: Water ChemComp-HOH / water / Water


Mass: 18.015 Da / Num. of mol.: 77 / 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: 2.78 Å3/Da / Density % sol: 55.75 %

-
Data collection

DiffractionMean temperature: 100 K
Diffraction sourceSource: ROTATING ANODE / Type: RIGAKU FR-E SUPERBRIGHT / Wavelength: 1.5418 Å
DetectorType: RIGAKU RAXIS IV++ / Detector: IMAGE PLATE / Details: VariMax Optics
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1.5418 Å / Relative weight: 1
ReflectionRedundancy: 3.74 % / Number: 117576 / Rmerge(I) obs: 0.155 / Χ2: 0.89 / D res high: 2 Å / D res low: 38.43 Å / Num. obs: 30265 / % possible obs: 99.8
Diffraction reflection shell

ID: 1

Highest resolution (Å)Lowest resolution (Å)% possible obs (%)Rmerge(I) obsChi squaredRedundancyRejects
4.3138.4398.70.1081.373.571481
3.424.3199.50.1371.413.61134
2.993.4299.80.1671.243.72634
2.712.9999.90.1811.043.77392
2.522.7199.80.2010.963.79297
2.372.521000.2140.793.8205
2.252.371000.2330.693.81131
2.152.251000.2650.673.8172
2.072.151000.2730.463.7839
22.071000.2970.43.7625
ReflectionResolution: 2→44 Å / Num. obs: 30265 / % possible obs: 99.8 % / Redundancy: 3.74 % / Rmerge(I) obs: 0.155 / Χ2: 0.89 / Net I/σ(I): 5.5 / Scaling rejects: 4410
Reflection shell

Diffraction-ID: 1

Resolution (Å)Redundancy (%)Rmerge(I) obsMean I/σ(I) obsNum. measured allNum. unique allΧ2% possible all
2-2.073.760.2972.31156730730.4100
2.07-2.153.780.2732.71141230070.46100
2.15-2.253.810.2653.21156930200.67100
2.25-2.373.810.2333.71166330300.69100
2.37-2.523.80.2144.31171830330.79100
2.52-2.713.790.2015.11177530280.9699.8
2.71-2.993.770.1815.81177630221.0499.9
2.99-3.423.720.1676.91195130401.2499.8
3.42-4.313.60.1379.31196630131.4199.5
4.31-38.433.570.108121217929991.3798.7

-
Processing

Software
NameVersionClassificationNB
d*TREK8.0SSIdata scaling
REFMACrefinement
PDB_EXTRACT3.1data extraction
RefinementMethod to determine structure: FOURIER SYNTHESIS / Resolution: 2→38.43 Å / Cor.coef. Fo:Fc: 0.926 / Cor.coef. Fo:Fc free: 0.91 / WRfactor Rfree: 0.2451 / WRfactor Rwork: 0.2198 / Occupancy max: 1 / Occupancy min: 0.5 / FOM work R set: 0.8567 / SU B: 3.919 / SU ML: 0.112 / SU R Cruickshank DPI: 0.1699 / SU Rfree: 0.1507 / Cross valid method: THROUGHOUT / σ(F): 0 / ESU R Free: 0.151 / Stereochemistry target values: MAXIMUM LIKELIHOOD / Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS
RfactorNum. reflection% reflectionSelection details
Rfree0.2401 2331 7.7 %RANDOM
Rwork0.2144 ---
obs0.2165 30263 99.78 %-
Solvent computationIon probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.2 Å / Solvent model: MASK
Displacement parametersBiso max: 54.42 Å2 / Biso mean: 25.7923 Å2 / Biso min: 13.66 Å2
Baniso -1Baniso -2Baniso -3
1--0.88 Å2-0.44 Å20 Å2
2---0.88 Å20 Å2
3---1.32 Å2
Refinement stepCycle: LAST / Resolution: 2→38.43 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms2477 0 32 77 2586
Refine LS restraints
Refine-IDTypeDev idealDev ideal targetNumber
X-RAY DIFFRACTIONr_bond_refined_d0.0150.0222586
X-RAY DIFFRACTIONr_angle_refined_deg1.4331.9623504
X-RAY DIFFRACTIONr_dihedral_angle_1_deg5.5795306
X-RAY DIFFRACTIONr_dihedral_angle_2_deg34.64923.71124
X-RAY DIFFRACTIONr_dihedral_angle_3_deg15.56915450
X-RAY DIFFRACTIONr_dihedral_angle_4_deg17.0581517
X-RAY DIFFRACTIONr_chiral_restr0.0970.2377
X-RAY DIFFRACTIONr_gen_planes_refined0.0060.021958
X-RAY DIFFRACTIONr_nbd_refined0.2030.21216
X-RAY DIFFRACTIONr_nbtor_refined0.2990.21771
X-RAY DIFFRACTIONr_xyhbond_nbd_refined0.130.2103
X-RAY DIFFRACTIONr_metal_ion_refined0.2210.22
X-RAY DIFFRACTIONr_symmetry_vdw_refined0.2080.236
X-RAY DIFFRACTIONr_symmetry_hbond_refined0.2250.26
X-RAY DIFFRACTIONr_mcbond_it0.8411.51588
X-RAY DIFFRACTIONr_mcangle_it1.26122479
X-RAY DIFFRACTIONr_scbond_it2.06431170
X-RAY DIFFRACTIONr_scangle_it3.0794.51025
LS refinement shellResolution: 2→2.052 Å / Total num. of bins used: 20
RfactorNum. reflection% reflection
Rfree0.339 180 -
Rwork0.26 2053 -
all-2233 -
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