[English] 日本語
Yorodumi
- PDB-6vbi: crystal structure of PDE5 in complex with a non-competitive inhibitor -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 6vbi
Titlecrystal structure of PDE5 in complex with a non-competitive inhibitor
ComponentscGMP-specific 3',5'-cyclic phosphodiesterase
KeywordsHYDROLASE/INHIBITOR / PDE5 / allosteric regulation / non-competitive inhibitors / HYDROLASE / 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 / cGMP catabolic process / positive regulation of cardiac muscle hypertrophy / 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 / 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 / negative regulation of T cell proliferation / T cell proliferation / cAMP-mediated signaling / 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 / GAF-like domain superfamily / Metal dependent phosphohydrolases with conserved 'HD' motif. / HD/PDEase domain
Similarity search - Domain/homology
Chem-FZA / cGMP-specific 3',5'-cyclic phosphodiesterase
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / MOLECULAR REPLACEMENT / Resolution: 2.30000752706 Å
AuthorsKe, H. / Luo, H.B.
CitationJournal: To Be Published
Title: Identification of a novel allosteric pocket and its regulation mechanism
Authors: Zhang, T. / Ke, H. / Luo, H.
History
DepositionDec 18, 2019Deposition site: RCSB / Processing site: RCSB
Revision 1.0Jan 20, 2021Provider: repository / Type: Initial release
Revision 1.1Oct 11, 2023Group: Data collection / Database references / Refinement description
Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / database_2 / pdbx_initial_refinement_model
Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession
Revision 1.2Oct 30, 2024Group: Structure summary / Category: pdbx_entry_details / pdbx_modification_feature / Item: _pdbx_entry_details.has_protein_modification

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

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


Theoretical massNumber of molelcules
Total (without water)76,0484
Polymers75,3212
Non-polymers7272
Water2,630146
1
A: cGMP-specific 3',5'-cyclic phosphodiesterase
hetero molecules


Theoretical massNumber of molelcules
Total (without water)38,0242
Polymers37,6601
Non-polymers3631
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
2
B: cGMP-specific 3',5'-cyclic phosphodiesterase
hetero molecules


Theoretical massNumber of molelcules
Total (without water)38,0242
Polymers37,6601
Non-polymers3631
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Unit cell
Length a, b, c (Å)65.975, 85.519, 124.381
Angle α, β, γ (deg.)90.000, 90.000, 90.000
Int Tables number19
Space group name H-MP212121
Space group name HallP2ac2ab
Symmetry operation#1: x,y,z
#2: x+1/2,-y+1/2,-z
#3: -x,y+1/2,-z+1/2
#4: -x+1/2,-y,z+1/2

-
Components

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


Mass: 37660.402 Da / Num. of mol.: 2
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: PDE5A, PDE5 / Production host: Escherichia coli (E. coli)
References: UniProt: O76074, 3',5'-cyclic-GMP phosphodiesterase
#2: Chemical ChemComp-FZA / (13bS)-4,9-dimethoxy-14-methyl-8,13,13b,14-tetrahydroindolo[2',3':3,4]pyrido[2,1-b]quinazolin-5(7H)-one


Mass: 363.410 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C21H21N3O3 / Feature type: SUBJECT OF INVESTIGATION
#3: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 146 / Source method: isolated from a natural source / Formula: H2O
Has ligand of interestY
Has protein modificationY

-
Experimental details

-
Experiment

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

-
Sample preparation

CrystalDensity Matthews: 2.51 Å3/Da / Density % sol: 51.07 %
Crystal growTemperature: 298 K / Method: evaporation
Details: 8% PEG3350, 0.2 M ammonium acetate, 0.1 M Na Acetate, pH 4.6

-
Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SEALED TUBE / Type: OXFORD DIFFRACTION NOVA / Wavelength: 1.54 Å
DetectorType: OXFORD ONYX CCD / Detector: CCD / Date: May 1, 2019
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1.54 Å / Relative weight: 1
ReflectionResolution: 2.3→50 Å / Num. obs: 31630 / % possible obs: 99.1 % / Redundancy: 4.5 % / Biso Wilson estimate: 24.4322830486 Å2 / Rmerge(I) obs: 0.099 / Net I/σ(I): 15.8
Reflection shellResolution: 2.3→2.38 Å / Redundancy: 3.7 % / Rmerge(I) obs: 0.464 / Num. unique obs: 2617 / % possible all: 96.9

-
Processing

Software
NameVersionClassification
PHENIX1.10_2155refinement
CrysalisPro38.41data reduction
CrysalisPro38.41data scaling
PHASER1.1phasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 2H40

2h40


Resolution: 2.30000752706→22.4594666497 Å / SU ML: 0.265536018902 / Cross valid method: NONE / σ(F): 1.35583161524 / Phase error: 23.0210635648
RfactorNum. reflection% reflection
Rfree0.252496556648 1549 4.89740428088 %
Rwork0.189212588836 --
obs0.192155296318 31629 99.0511086058 %
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å
Displacement parametersBiso mean: 29.4860807999 Å2
Refinement stepCycle: LAST / Resolution: 2.30000752706→22.4594666497 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms4950 0 0 146 5096
Refine LS restraints
Refine-IDTypeDev idealNumber
X-RAY DIFFRACTIONf_bond_d0.007675614149735054
X-RAY DIFFRACTIONf_angle_d0.9212463825586839
X-RAY DIFFRACTIONf_chiral_restr0.0485858032638767
X-RAY DIFFRACTIONf_plane_restr0.00612597819706928
X-RAY DIFFRACTIONf_dihedral_angle_d15.32064001163097
LS refinement shell
Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkRefine-ID% reflection obs (%)
2.31-2.37420.3073087138811300.2345821792072617X-RAY DIFFRACTION97.1014492754
2.3742-2.45890.3048167132661500.2391264791082655X-RAY DIFFRACTION97.1933471933
2.4589-2.55720.2744263693541360.2346657458632669X-RAY DIFFRACTION98.6633837496
2.5572-2.67340.3044635457981310.2183092421672728X-RAY DIFFRACTION100
2.6734-2.81410.3027108315761490.211406399862729X-RAY DIFFRACTION100
2.8141-2.99010.2833408246441580.2067978516852734X-RAY DIFFRACTION100
2.9901-3.22030.2654602433581500.2032682242222730X-RAY DIFFRACTION100
3.2203-3.54330.2145919513571270.1782482902292764X-RAY DIFFRACTION100
3.5433-4.05340.2223290393111330.1592437700032788X-RAY DIFFRACTION99.8974008208
4.0534-5.0970.2286366362741320.1602718623132808X-RAY DIFFRACTION99.3578911795
5.097-22.450.2139701651981530.1719424092652858X-RAY DIFFRACTION97.4749109744

+
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