[English] 日本語
Yorodumi
- PDB-7faq: Crystal structure of PDE5A in complex with inhibitor L1 -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 7faq
TitleCrystal structure of PDE5A in complex with inhibitor L1
ComponentscGMP-specific 3',5'-cyclic phosphodiesterase
KeywordsHYDROLASE/INHIBITOR / HYDROLASE-INHIBITOR COMPLEX
Function / homology
Function and homology information


positive regulation of oocyte development / 3',5'-cyclic-GMP phosphodiesterase / regulation of nitric oxide mediated signal transduction / negative regulation of cardiac muscle contraction / oocyte development / RHOBTB1 GTPase cycle / relaxation of cardiac muscle / positive regulation of cardiac muscle hypertrophy / cGMP catabolic process / cGMP effects ...positive regulation of oocyte development / 3',5'-cyclic-GMP phosphodiesterase / regulation of nitric oxide mediated signal transduction / negative regulation of cardiac muscle contraction / oocyte development / RHOBTB1 GTPase cycle / relaxation of cardiac muscle / positive regulation of cardiac muscle hypertrophy / cGMP catabolic process / cGMP effects / 3',5'-cyclic-nucleotide phosphodiesterase activity / cGMP binding / Smooth Muscle Contraction / 3',5'-cyclic-GMP phosphodiesterase activity / 3',5'-cyclic-AMP phosphodiesterase activity / T cell proliferation / negative regulation of T cell proliferation / cAMP-mediated signaling / metal ion binding / cytosol
Similarity search - Function
3'5'-cyclic nucleotide phosphodiesterase / GAF domain / 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. / Domain present in phytochromes and cGMP-specific phosphodiesterases. / GAF domain ...3'5'-cyclic nucleotide phosphodiesterase / GAF domain / 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. / Domain present in phytochromes and cGMP-specific phosphodiesterases. / GAF domain / GAF-like domain superfamily / Metal dependent phosphohydrolases with conserved 'HD' motif. / HD/PDEase domain
Similarity search - Domain/homology
Chem-2OI / cGMP-specific 3',5'-cyclic phosphodiesterase
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / MOLECULAR REPLACEMENT / Resolution: 2.20013606546 Å
AuthorsWu, D. / Huang, Y.Y. / Luo, H.B.
Funding support China, 3items
OrganizationGrant numberCountry
National Natural Science Foundation of China (NSFC)81872727 China
National Natural Science Foundation of China (NSFC)81602955 China
National Natural Science Foundation of China (NSFC)21702238 China
CitationJournal: Acta Pharm Sin B / Year: 2022
Title: Free energy perturbation (FEP)-guided scaffold hopping.
Authors: Wu, D. / Zheng, X. / Liu, R. / Li, Z. / Jiang, Z. / Zhou, Q. / Huang, Y. / Wu, X.N. / Zhang, C. / Huang, Y.Y. / Luo, H.B.
History
DepositionJul 7, 2021Deposition site: PDBJ / Processing site: PDBJ
Revision 1.0May 18, 2022Provider: repository / Type: Initial release
Revision 1.1Nov 29, 2023Group: Data collection / Refinement description
Category: chem_comp_atom / chem_comp_bond / pdbx_initial_refinement_model

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: cGMP-specific 3',5'-cyclic phosphodiesterase
hetero molecules


Theoretical massNumber of molelcules
Total (without water)40,7935
Polymers40,2661
Non-polymers5274
Water1,29772
1


  • Idetical with deposited unit
  • defined by author&software
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area320 Å2
ΔGint-52 kcal/mol
Surface area12800 Å2
MethodPISA
Unit cell
Length a, b, c (Å)73.875, 73.875, 131.855
Angle α, β, γ (deg.)90.000, 90.000, 120.000
Int Tables number152
Space group name H-MP3121
Space group name HallP312"
Symmetry operation#1: x,y,z
#2: -y,x-y,z+1/3
#3: -x+y,-x,z+2/3
#4: x-y,-y,-z+2/3
#5: -x,-x+y,-z+1/3
#6: y,x,-z

-
Components

-
Protein , 1 types, 1 molecules A

#1: Protein cGMP-specific 3',5'-cyclic phosphodiesterase / cGMP-binding cGMP-specific phosphodiesterase / CGB-PDE


Mass: 40266.242 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: PDE5A, PDE5 / Production host: Escherichia coli BL21 (bacteria) / Strain (production host): BL21
References: UniProt: O76074, 3',5'-cyclic-GMP phosphodiesterase

-
Non-polymers , 5 types, 76 molecules

#2: Chemical ChemComp-ZN / ZINC ION


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


Mass: 24.305 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: Mg
#4: Chemical ChemComp-SO4 / SULFATE ION


Mass: 96.063 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: SO4
#5: Chemical ChemComp-2OI / 2-[(4-chlorophenyl)methyl]-5-methoxy-3,10-diazatricyclo[6.4.1.0^{4,13}]trideca-1,4(13),5,7-tetraen-9-one


Mass: 340.803 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C19H17ClN2O2 / Feature type: SUBJECT OF INVESTIGATION
#6: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 72 / Source method: isolated from a natural source / Formula: H2O

-
Details

Has ligand of interestY

-
Experimental details

-
Experiment

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

-
Sample preparation

CrystalDensity Matthews: 2.58 Å3/Da / Density % sol: 52.32 %
Crystal growTemperature: 277 K / Method: vapor diffusion, hanging drop
Details: 0.2 M magnesium sulfate, 0.1 M sodium cacodylate, pH 6.5, 17% PEG3350

-
Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: ROTATING ANODE / Type: RIGAKU / Wavelength: 1.54056 Å
DetectorType: RIGAKU HyPix-3000 / Detector: PIXEL / Date: Aug 3, 2020
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1.54056 Å / Relative weight: 1
ReflectionResolution: 2.2→22.71 Å / Num. obs: 21798 / % possible obs: 99.81 % / Redundancy: 8.1 % / Biso Wilson estimate: 42.9547344485 Å2 / Rmerge(I) obs: 0.054 / Net I/σ(I): 33
Reflection shellResolution: 2.2→2.28 Å / Redundancy: 5.7 % / Rmerge(I) obs: 0.572 / Mean I/σ(I) obs: 2.7 / Num. unique obs: 2186 / % possible all: 100

-
Processing

Software
NameVersionClassification
PHENIX1.10_2155refinement
CrysalisProdata reduction
CrysalisProdata scaling
PHASERphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 4md6

4md6


Resolution: 2.20013606546→22.7022391169 Å / SU ML: 0.304886308095 / Cross valid method: NONE / σ(F): 1.36058762158 / Phase error: 29.6972174003
Stereochemistry target values: GeoStd + Monomer Library + CDL v1.2
RfactorNum. reflection% reflection
Rfree0.272067669888 1099 5.05171225006 %
Rwork0.225164311103 20656 -
obs0.227501476184 21755 99.9632403621 %
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT BULK SOLVENT MODEL
Displacement parametersBiso mean: 49.9247361213 Å2
Refinement stepCycle: LAST / Resolution: 2.20013606546→22.7022391169 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms2312 0 31 72 2415
Refine LS restraints
Refine-IDTypeDev idealNumber
X-RAY DIFFRACTIONf_bond_d0.009369461126832387
X-RAY DIFFRACTIONf_angle_d1.171081394663224
X-RAY DIFFRACTIONf_chiral_restr0.0472328770355364
X-RAY DIFFRACTIONf_plane_restr0.0058861027772430
X-RAY DIFFRACTIONf_dihedral_angle_d15.53358728691454
LS refinement shell
Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkRefine-ID% reflection obs (%)
2.20014-2.30020.366091429771370.3323999378162538X-RAY DIFFRACTION99.7762029094
2.3002-2.42130.3282094375011250.3050136583132533X-RAY DIFFRACTION100
2.4213-2.57280.2842734311741340.2838629641862553X-RAY DIFFRACTION100
2.5728-2.77120.2956022693351630.2644341318142528X-RAY DIFFRACTION100
2.7712-3.04940.3454540544231340.2674634511732565X-RAY DIFFRACTION100
3.0494-3.48930.2911109423011590.2294972370062557X-RAY DIFFRACTION100
3.4893-4.3910.2477137992351240.1983869584792624X-RAY DIFFRACTION100
4.391-22.70210.2233482714361230.1879038516712758X-RAY DIFFRACTION99.9306278182

+
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://pdbjlvh1.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