[English] 日本語
Yorodumi
- PDB-6o5s: Room temperature structure of VX-phosphonylated hAChE in complex ... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 6o5s
TitleRoom temperature structure of VX-phosphonylated hAChE in complex with oxime reactivator RS-170B
ComponentsAcetylcholinesterase
KeywordsHYDROLASE / VX-phosphonylated / VX-hAChE / oxime reactivator / imidazole-based oxime / RS-170B
Function / homology
Function and homology information


negative regulation of synaptic transmission, cholinergic / Neurotransmitter clearance / serine hydrolase activity / acetylcholine catabolic process in synaptic cleft / cholinesterase activity / acetylcholine catabolic process / acetylcholine binding / acetylcholinesterase / amyloid precursor protein metabolic process / acetylcholine receptor signaling pathway ...negative regulation of synaptic transmission, cholinergic / Neurotransmitter clearance / serine hydrolase activity / acetylcholine catabolic process in synaptic cleft / cholinesterase activity / acetylcholine catabolic process / acetylcholine binding / acetylcholinesterase / amyloid precursor protein metabolic process / acetylcholine receptor signaling pathway / osteoblast development / acetylcholinesterase activity / Synthesis of PC / basement membrane / regulation of receptor recycling / Synthesis, secretion, and deacylation of Ghrelin / synaptic cleft / side of membrane / laminin binding / collagen binding / synapse assembly / positive regulation of protein secretion / neuromuscular junction / receptor internalization / positive regulation of cold-induced thermogenesis / retina development in camera-type eye / nervous system development / amyloid-beta binding / cell adhesion / hydrolase activity / synapse / perinuclear region of cytoplasm / Golgi apparatus / cell surface / protein homodimerization activity / extracellular space / extracellular region / membrane / nucleus / plasma membrane
Similarity search - Function
Acetylcholinesterase, tetramerisation domain / Acetylcholinesterase tetramerisation domain / : / Cholinesterase / Carboxylesterase type B, conserved site / Carboxylesterases type-B signature 2. / Carboxylesterase type B, active site / Carboxylesterases type-B serine active site. / Carboxylesterase, type B / Carboxylesterase family ...Acetylcholinesterase, tetramerisation domain / Acetylcholinesterase tetramerisation domain / : / Cholinesterase / Carboxylesterase type B, conserved site / Carboxylesterases type-B signature 2. / Carboxylesterase type B, active site / Carboxylesterases type-B serine active site. / Carboxylesterase, type B / Carboxylesterase family / Alpha/Beta hydrolase fold, catalytic domain / Alpha/Beta hydrolase fold / Rossmann fold / 3-Layer(aba) Sandwich / Alpha Beta
Similarity search - Domain/homology
Chem-LND / O-ETHYLMETHYLPHOSPHONIC ACID ESTER GROUP / Acetylcholinesterase
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.801 Å
AuthorsGerlits, O. / Kovalevsky, A. / Radic, Z.
Funding support United States, 1items
OrganizationGrant numberCountry
National Institutes of Health/National Institute of Neurological Disorders and Stroke (NIH/NINDS)1U01NS083451 United States
CitationJournal: J.Biol.Chem. / Year: 2019
Title: Productive reorientation of a bound oxime reactivator revealed in room temperature X-ray structures of native and VX-inhibited human acetylcholinesterase.
Authors: Gerlits, O. / Kong, X. / Cheng, X. / Wymore, T. / Blumenthal, D.K. / Taylor, P. / Radic, Z. / Kovalevsky, A.
History
DepositionMar 4, 2019Deposition site: RCSB / Processing site: RCSB
Revision 1.0May 29, 2019Provider: repository / Type: Initial release
Revision 1.1Jun 12, 2019Group: Data collection / Database references / Category: citation / citation_author
Item: _citation.pdbx_database_id_DOI / _citation.pdbx_database_id_PubMed ..._citation.pdbx_database_id_DOI / _citation.pdbx_database_id_PubMed / _citation.title / _citation_author.identifier_ORCID
Revision 1.2Jul 17, 2019Group: Data collection / Database references / Category: citation
Item: _citation.journal_volume / _citation.page_first ..._citation.journal_volume / _citation.page_first / _citation.page_last / _citation.title
Revision 1.3Dec 18, 2019Group: Author supporting evidence / Category: pdbx_audit_support / Item: _pdbx_audit_support.funding_organization
Revision 1.4Oct 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

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Acetylcholinesterase
B: Acetylcholinesterase
hetero molecules


Theoretical massNumber of molelcules
Total (without water)121,6218
Polymers120,5762
Non-polymers1,0456
Water2,990166
1


  • Idetical with deposited unit
  • defined by author
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area2600 Å2
ΔGint21 kcal/mol
Surface area39870 Å2
2
A: Acetylcholinesterase
hetero molecules

B: Acetylcholinesterase
hetero molecules


Theoretical massNumber of molelcules
Total (without water)121,6218
Polymers120,5762
Non-polymers1,0456
Water362
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
crystal symmetry operation3_554-x+y,-x,z-1/31
Buried area3460 Å2
ΔGint13 kcal/mol
Surface area39020 Å2
MethodPISA
Unit cell
Length a, b, c (Å)125.557, 125.557, 130.861
Angle α, β, γ (deg.)90.00, 90.00, 120.00
Int Tables number144
Space group name H-MP31

-
Components

#1: Protein Acetylcholinesterase / AChE


Mass: 60287.977 Da / Num. of mol.: 2 / Fragment: residues 33-574
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: ACHE / Cell line (production host): HEK293 / Production host: Homo sapiens (human) / References: UniProt: P22303, acetylcholinesterase
#2: Chemical
ChemComp-VX / O-ETHYLMETHYLPHOSPHONIC ACID ESTER GROUP


Mass: 124.076 Da / Num. of mol.: 4
Source method: isolated from a genetically manipulated source
Formula: C3H9O3P
#3: Chemical ChemComp-LND / 4-carbamoyl-1-(3-{2-[(E)-(hydroxyimino)methyl]-1H-imidazol-1-yl}propyl)pyridin-1-ium


Mass: 274.298 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C13H16N5O2
#4: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 166 / 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: 5.03 Å3/Da / Density % sol: 75.54 %
Crystal growTemperature: 283 K / Method: vapor diffusion, sitting drop / pH: 7
Details: 10 mM sodium citrate, 100 mM HEPES, pH 7, and 6-8 % PEG6000

-
Data collection

DiffractionMean temperature: 293 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: APS / Beamline: 19-ID / Wavelength: 0.92 Å
DetectorType: DECTRIS PILATUS3 X 6M / Detector: PIXEL / Date: Mar 12, 2018
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.92 Å / Relative weight: 1
ReflectionResolution: 2.8→40 Å / Num. obs: 52095 / % possible obs: 96.7 % / Redundancy: 2.7 % / Rmerge(I) obs: 0.069 / Net I/σ(I): 11.7
Reflection shellResolution: 2.8→2.9 Å / Rmerge(I) obs: 0.739 / Num. unique obs: 5383

-
Processing

Software
NameVersionClassification
PHENIX(1.11_2567)refinement
HKL-3000data reduction
HKL-3000data scaling
PHASERphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 4EY4

4ey4


Resolution: 2.801→39.21 Å / SU ML: 0.33 / Cross valid method: FREE R-VALUE / σ(F): 1.98 / Phase error: 20.81
RfactorNum. reflection% reflection
Rfree0.1986 2584 4.96 %
Rwork0.1707 --
obs0.172 52095 91.75 %
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å
Refinement stepCycle: LAST / Resolution: 2.801→39.21 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms8376 0 66 166 8608
Refine LS restraints
Refine-IDTypeDev idealNumber
X-RAY DIFFRACTIONf_bond_d0.0028729
X-RAY DIFFRACTIONf_angle_d0.47211939
X-RAY DIFFRACTIONf_dihedral_angle_d13.0915109
X-RAY DIFFRACTIONf_chiral_restr0.0421258
X-RAY DIFFRACTIONf_plane_restr0.0051582
LS refinement shell
Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkRefine-ID% reflection obs (%)
2.8005-2.85440.37161020.32621453X-RAY DIFFRACTION49
2.8544-2.91260.35131240.29611964X-RAY DIFFRACTION66
2.9126-2.97590.32641720.28292630X-RAY DIFFRACTION89
2.9759-3.04510.28481170.27452899X-RAY DIFFRACTION96
3.0451-3.12130.321670.26022929X-RAY DIFFRACTION97
3.1213-3.20560.23371410.24012911X-RAY DIFFRACTION97
3.2056-3.29990.27341410.21522972X-RAY DIFFRACTION97
3.2999-3.40640.23191400.20632875X-RAY DIFFRACTION97
3.4064-3.5280.20371680.18322848X-RAY DIFFRACTION96
3.528-3.66920.20051520.18082774X-RAY DIFFRACTION93
3.6692-3.8360.17341280.16413008X-RAY DIFFRACTION99
3.836-4.03810.15231980.14652902X-RAY DIFFRACTION98
4.0381-4.29080.1361400.13632958X-RAY DIFFRACTION98
4.2908-4.62160.14361430.12982881X-RAY DIFFRACTION96
4.6216-5.08580.15251470.13372828X-RAY DIFFRACTION95
5.0858-5.81970.18141480.14652955X-RAY DIFFRACTION99
5.8197-7.32440.19611290.15212827X-RAY DIFFRACTION94
7.3244-39.21380.17381270.12372897X-RAY DIFFRACTION96

+
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