[English] 日本語
Yorodumi
- PDB-8xww: Crystal structure of the catalytic domain of human PDE5A complexe... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 8xww
TitleCrystal structure of the catalytic domain of human PDE5A complexed with 2-(3-chlorobenzyl)-4-oxo-3,4-dihydroquinazoline-7-carboxylic acid
ComponentsIsoform PDE5A1 of cGMP-specific 3',5'-cyclic phosphodiesterase
KeywordsHYDROLASE / Inhibitor / Complex
Function / homology
Function and homology information


positive regulation of oocyte development / 3',5'-cyclic-GMP phosphodiesterase / calmodulin-activated dual specificity 3',5'-cyclic-GMP, 3',5'-cyclic-AMP phosphodiesterase activity / calmodulin-activated 3',5'-cyclic-GMP phosphodiesterase activity / regulation of nitric oxide mediated signal transduction / negative regulation of cardiac muscle contraction / oocyte development / RHOBTB1 GTPase cycle / relaxation of cardiac muscle / cGMP catabolic process ...positive regulation of oocyte development / 3',5'-cyclic-GMP phosphodiesterase / calmodulin-activated dual specificity 3',5'-cyclic-GMP, 3',5'-cyclic-AMP phosphodiesterase activity / calmodulin-activated 3',5'-cyclic-GMP phosphodiesterase activity / regulation of nitric oxide mediated signal transduction / negative regulation of cardiac muscle contraction / oocyte development / RHOBTB1 GTPase cycle / relaxation of cardiac muscle / cGMP catabolic process / positive regulation of cardiac muscle hypertrophy / cGMP effects / 3',5'-cyclic-nucleotide phosphodiesterase activity / cGMP binding / 3',5'-cyclic-GMP phosphodiesterase activity / Smooth Muscle Contraction / 3',5'-cyclic-AMP phosphodiesterase activity / cAMP-mediated signaling / T cell proliferation / negative regulation of T cell proliferation / 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
: / cGMP-specific 3',5'-cyclic phosphodiesterase
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / MOLECULAR REPLACEMENT / Resolution: 2.46 Å
AuthorsZhang, F.C. / Huang, Y.Y. / Luo, H.B. / Wu, Y.Y.
Funding support China, 2items
OrganizationGrant numberCountry
National Natural Science Foundation of China (NSFC)21977127 China
National Natural Science Foundation of China (NSFC)22077143 China
CitationJournal: To Be Published
Title: Discovery of Highly Potent and Selective PDE5 Inhibitors for the Treatment of Idiopathic Pulmonary Fibrosis
Authors: Zhang, F.C. / Huang, Y.Y. / Luo, H.B. / Wu, Y.Y.
History
DepositionJan 16, 2024Deposition site: PDBJ / Processing site: PDBC
Revision 1.0Jan 22, 2025Provider: repository / Type: Initial release

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Isoform PDE5A1 of cGMP-specific 3',5'-cyclic phosphodiesterase
hetero molecules


Theoretical massNumber of molelcules
Total (without water)40,6714
Polymers40,2661
Non-polymers4043
Water1,20767
1


  • Idetical with deposited unit
  • defined by author
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Unit cell
Length a, b, c (Å)74.261, 74.261, 131.943
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

#1: Protein Isoform PDE5A1 of 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(DE3) (bacteria)
References: UniProt: O76074, 3',5'-cyclic-GMP phosphodiesterase
#2: Chemical ChemComp-A1D5K / 2-[(3-chlorophenyl)methyl]-4-oxidanylidene-3~{H}-quinazoline-7-carboxylic acid


Mass: 314.723 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C16H11ClN2O3 / Feature type: SUBJECT OF INVESTIGATION
#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: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 67 / Source method: isolated from a natural source / Formula: H2O
Has ligand of interestY
Has protein modificationN

-
Experimental details

-
Experiment

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

-
Sample preparation

CrystalDensity Matthews: 2.61 Å3/Da / Density % sol: 52.84 %
Crystal growTemperature: 298 K / Method: vapor diffusion, hanging drop / pH: 6.5
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: 1.54184 Å
DetectorType: RIGAKU HyPix-3000 / Detector: PIXEL / Date: Nov 7, 2022
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1.54184 Å / Relative weight: 1
ReflectionResolution: 2.46→23.91 Å / Num. obs: 15861 / % possible obs: 99.9 % / Redundancy: 9 % / CC1/2: 0.999 / Rmerge(I) obs: 0.072 / Net I/σ(I): 25.5
Reflection shellResolution: 2.46→2.56 Å / Rmerge(I) obs: 0.746 / Num. unique obs: 1764 / CC1/2: 0.763 / % possible all: 100

-
Processing

Software
NameVersionClassification
PHENIXPhenix1.16-3549refinement
CrysalisProdata scaling
PHASERphasing
CrysalisProdata reduction
RefinementMethod to determine structure: MOLECULAR REPLACEMENT / Resolution: 2.46→23.91 Å / Cross valid method: THROUGHOUT
Stereochemistry target values: GeoStd + Monomer Library + CDL v1.2
RfactorNum. reflection% reflection
Rfree0.2672 --
Rwork0.2351 --
obs-15822 100 %
Displacement parametersBiso mean: 55.02 Å2
Refinement stepCycle: LAST / Resolution: 2.46→23.91 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms2357 0 24 67 2448

+
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