[English] 日本語
Yorodumi
- PDB-5shr: CRYSTAL STRUCTURE OF HUMAN PHOSPHODIESTERASE 10 IN COMPLEX WITH n... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 5shr
TitleCRYSTAL STRUCTURE OF HUMAN PHOSPHODIESTERASE 10 IN COMPLEX WITH n1(c(nc(n1)c2ccccc2)N(C)Cc4nn3c(cnc(c3n4)C)C)C, micromolar IC50=1.47052
Components(cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase ...) x 2
KeywordsHYDROLASE/HYDROLASE inhibitor / PHOSPHODIESTERASE / PDE10 / HYDROLASE / HYDROLASE-HYDROLASE inhibitor complex
Function / homology
Function and homology information


3',5'-cGMP-stimulated cyclic-nucleotide phosphodiesterase activity / 3',5'-cyclic-nucleotide phosphodiesterase / negative regulation of receptor guanylyl cyclase signaling pathway / cGMP catabolic process / cAMP catabolic process / regulation of cAMP/PKA signal transduction / cGMP effects / 3',5'-cyclic-nucleotide phosphodiesterase activity / cGMP binding / regulation of adenylate cyclase-activating G protein-coupled receptor signaling pathway ...3',5'-cGMP-stimulated cyclic-nucleotide phosphodiesterase activity / 3',5'-cyclic-nucleotide phosphodiesterase / negative regulation of receptor guanylyl cyclase signaling pathway / cGMP catabolic process / cAMP catabolic process / regulation of cAMP/PKA signal transduction / cGMP effects / 3',5'-cyclic-nucleotide phosphodiesterase activity / cGMP binding / regulation of adenylate cyclase-activating G protein-coupled receptor signaling pathway / 3',5'-cyclic-GMP phosphodiesterase activity / 3',5'-cyclic-AMP phosphodiesterase activity / : / cAMP binding / G alpha (s) signalling events / glutamatergic synapse / metal ion binding / cytosol
Similarity search - Function
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 ...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
Similarity search - Domain/homology
Chem-JIP / cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 1.98 Å
AuthorsJoseph, C. / Benz, J. / Flohr, A. / Rudolph, M.G.
Funding support Switzerland, 1items
OrganizationGrant numberCountry
F. Hoffmann-La Roche Switzerland
CitationJournal: To be published
Title: Crystal Structure of a human phosphodiesterase 10 complex
Authors: Flohr, A. / Schlatter, D. / Kuhn, B. / Rudolph, M.G.
History
DepositionFeb 1, 2022Deposition site: RCSB / Processing site: RCSB
Revision 1.0Oct 19, 2022Provider: repository / Type: Initial release
Revision 1.1Apr 3, 2024Group: Data collection / Refinement description
Category: chem_comp_atom / chem_comp_bond / pdbx_initial_refinement_model
Revision 1.2Oct 16, 2024Group: Structure summary
Category: pdbx_entry_details / pdbx_modification_feature / struct
Item: _pdbx_entry_details.has_protein_modification / _struct.title

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A
B: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A
C: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A
D: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A
hetero molecules


Theoretical massNumber of molelcules
Total (without water)159,48116
Polymers157,7294
Non-polymers1,75212
Water8,989499
1
A: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A
hetero molecules


Theoretical massNumber of molelcules
Total (without water)39,9274
Polymers39,4891
Non-polymers4383
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
2
B: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A
hetero molecules


Theoretical massNumber of molelcules
Total (without water)39,8514
Polymers39,4131
Non-polymers4383
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
3
C: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A
hetero molecules


Theoretical massNumber of molelcules
Total (without water)39,8514
Polymers39,4131
Non-polymers4383
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
4
D: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A
hetero molecules


Theoretical massNumber of molelcules
Total (without water)39,8514
Polymers39,4131
Non-polymers4383
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Unit cell
Length a, b, c (Å)135.115, 135.115, 234.836
Angle α, β, γ (deg.)90.000, 90.000, 120.000
Int Tables number146
Space group name H-MH3

-
Components

-
CAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase ... , 2 types, 4 molecules ABCD

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


Mass: 39489.324 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: PDE10A / Plasmid: PET28a(+) / Production host: Escherichia coli BL21(DE3) (bacteria)
References: UniProt: Q9Y233, 3',5'-cyclic-nucleotide phosphodiesterase
#2: Protein cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A


Mass: 39413.203 Da / Num. of mol.: 3
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: PDE10A / Plasmid: PET28a(+) / Production host: Escherichia coli BL21(DE3) (bacteria)
References: UniProt: Q9Y233, 3',5'-cyclic-nucleotide phosphodiesterase

-
Non-polymers , 4 types, 511 molecules

#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: Chemical
ChemComp-JIP / N-{[(4R)-5,8-dimethyl[1,2,4]triazolo[1,5-a]pyrazin-2-yl]methyl}-N,1-dimethyl-3-phenyl-1H-1,2,4-triazol-5-amine


Mass: 348.405 Da / Num. of mol.: 4 / Source method: obtained synthetically / Formula: C18H20N8 / Feature type: SUBJECT OF INVESTIGATION
#6: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 499 / Source method: isolated from a natural source / Formula: H2O

-
Details

Has ligand of interestY
Has protein modificationY

-
Experimental details

-
Experiment

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

-
Sample preparation

CrystalDensity Matthews: 2.62 Å3/Da / Density % sol: 52.97 %
Crystal growTemperature: 295 K / Method: vapor diffusion, sitting drop / pH: 7.5
Details: 5-20 mg/mL protein in 25mM HEPES/NaOH pH7.5, 150mM NaCl, 50mM BME mixed 1:1 with reservoir 0.1M HEPES/NaOH pH7.5, 30% PEG550MME, 50mM MgCl2

-
Data collection

DiffractionMean temperature: 100 K
Diffraction sourceSource: SYNCHROTRON / Site: SLS / Beamline: X10SA / Wavelength: 1 Å
DetectorType: PSI PILATUS 6M / Detector: PIXEL / Date: Mar 17, 2013
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1 Å / Relative weight: 1
ReflectionResolution: 1.98→43.46 Å / Num. obs: 111088 / % possible obs: 99.8 % / Redundancy: 5.122 % / Biso Wilson estimate: 42.152 Å2 / CC1/2: 0.999 / Rmerge(I) obs: 0.073 / Rrim(I) all: 0.081 / Χ2: 0.865 / Net I/σ(I): 15.28 / Num. measured all: 569024 / Scaling rejects: 265
Reflection shell

Diffraction-ID: 1

Resolution (Å)Redundancy (%)Rmerge(I) obsMean I/σ(I) obsNum. measured obsNum. possibleNum. unique obsCC1/2Rrim(I) all% possible all
1.98-2.035.2151.3341.1842551817381590.4681.48599.8
2.03-2.094.91.2011.4439197808479990.581.34998.9
2.09-2.154.8960.8451.8938218781578060.6770.94899.9
2.15-2.215.0780.5472.938657761576120.8350.611100
2.21-2.295.0550.5423.3636599730972400.860.60799.1
2.29-2.375.3060.344.6937765712071170.9320.378100
2.37-2.465.2230.2685.7435935688568800.9570.29999.9
2.46-2.564.9830.2176.9832605654865430.9680.24299.9
2.56-2.674.9120.1669.0430987631163080.9790.186100
2.67-2.85.3330.13311.4532413608060780.9870.148100
2.8-2.955.3720.10114.6930862574857450.9930.11299.9
2.95-3.135.3220.07718.8728891543154290.9960.085100
3.13-3.354.9920.05824.425811517051700.9970.064100
3.35-3.615.0560.04233.2623847472047170.9980.04799.9
3.61-3.965.2060.03640.9522833439243860.9990.0499.9
3.96-4.435.2690.02948.0120812395439500.9990.03299.9
4.43-5.114.9190.02650.2517118348034800.9990.029100
5.11-6.265.3260.02749.5215657294029400.9990.03100
6.26-8.855.1790.02255.58118442289228710.02599.9
8.85-43.465.1710.01767.4264221252124210.01999.2

-
Processing

Software
NameVersionClassificationNB
XSCALEdata scaling
REFMAC5.8.0267refinement
PDB_EXTRACT3.27data extraction
XDSdata reduction
XSCALEdata scaling
PHASERphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: inhouse model

Resolution: 1.98→43.46 Å / Cor.coef. Fo:Fc: 0.957 / Cor.coef. Fo:Fc free: 0.938 / SU B: 5.541 / SU ML: 0.138 / Cross valid method: THROUGHOUT / σ(F): 0 / ESU R: 0.178 / ESU R Free: 0.165 / Stereochemistry target values: MAXIMUM LIKELIHOOD
Details: ligand conformation in mol A best supported by electron density. clash with methionine SD. methyl group kept in plane with tertiary amine though no conjugation with triazole. pyramidal amine ...Details: ligand conformation in mol A best supported by electron density. clash with methionine SD. methyl group kept in plane with tertiary amine though no conjugation with triazole. pyramidal amine not supported by electron density, but in principle possible. other protomers have clash of methyl group with Phe.
RfactorNum. reflection% reflectionSelection details
Rfree0.2301 4888 5 %RANDOM
Rwork0.182 ---
obs0.1844 92911 87.86 %-
Solvent computationIon probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.2 Å / Solvent model: MASK
Displacement parametersBiso max: 120.39 Å2 / Biso mean: 38.36 Å2 / Biso min: 17.62 Å2
Baniso -1Baniso -2Baniso -3
1--0.48 Å2-0.24 Å20 Å2
2---0.48 Å20 Å2
3---1.57 Å2
Refinement stepCycle: final / Resolution: 1.98→43.46 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms10161 0 112 499 10772
Biso mean--49.07 39.24 -
Num. residues----1251
Refine LS restraints
Refine-IDTypeDev idealDev ideal targetNumber
X-RAY DIFFRACTIONr_bond_refined_d0.0140.01310555
X-RAY DIFFRACTIONr_bond_other_d0.0010.0179880
X-RAY DIFFRACTIONr_angle_refined_deg1.8971.65714304
X-RAY DIFFRACTIONr_angle_other_deg1.4671.58422766
X-RAY DIFFRACTIONr_dihedral_angle_1_deg6.01251255
X-RAY DIFFRACTIONr_dihedral_angle_2_deg36.0622.582550
X-RAY DIFFRACTIONr_dihedral_angle_3_deg16.395151850
X-RAY DIFFRACTIONr_dihedral_angle_4_deg21.1211557
X-RAY DIFFRACTIONr_chiral_restr0.0920.21349
X-RAY DIFFRACTIONr_gen_planes_refined0.0110.0211798
X-RAY DIFFRACTIONr_gen_planes_other0.0010.022456
X-RAY DIFFRACTIONr_mcbond_it3.6543.7925008
X-RAY DIFFRACTIONr_mcbond_other3.6513.7915006
X-RAY DIFFRACTIONr_mcangle_it4.6855.6716255
LS refinement shellResolution: 1.98→2.031 Å / Rfactor Rfree error: 0 / Total num. of bins used: 20
RfactorNum. reflection% reflection
Rfree0.374 362 -
Rwork0.36 6958 -
all-7320 -
obs--89.76 %

+
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