[English] 日本語
Yorodumi
- PDB-8p3e: Crystal structure of glucocerebrosidase in complex with allosteri... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 8p3e
TitleCrystal structure of glucocerebrosidase in complex with allosteric activator
ComponentsGlucosylceramidase
KeywordsHYDROLASE / Activator / lysosome / glycolipid metabolism
Function / homology
Function and homology information


positive regulation of protein lipidation / steryl-beta-glucosidase activity / beta-glucoside catabolic process / cerebellar Purkinje cell layer formation / positive regulation of neuronal action potential / : / termination of signal transduction / galactosylceramidase / galactosylceramidase activity / lymphocyte migration ...positive regulation of protein lipidation / steryl-beta-glucosidase activity / beta-glucoside catabolic process / cerebellar Purkinje cell layer formation / positive regulation of neuronal action potential / : / termination of signal transduction / galactosylceramidase / galactosylceramidase activity / lymphocyte migration / glucosylceramidase / scavenger receptor binding / glucosylceramide catabolic process / regulation of lysosomal protein catabolic process / autophagosome organization / glucosylceramidase activity / sphingosine biosynthetic process / microglial cell proliferation / regulation of TOR signaling / glucosyltransferase activity / lipid storage / response to thyroid hormone / ceramide biosynthetic process / microglia differentiation / Glycosphingolipid catabolism / pyramidal neuron differentiation / lipid glycosylation / brain morphogenesis / Hydrolases; Glycosylases; Glycosidases, i.e. enzymes that hydrolyse O- and S-glycosyl compounds / response to pH / positive regulation of protein-containing complex disassembly / motor behavior / neuromuscular process / Transferases; Glycosyltransferases; Hexosyltransferases / hematopoietic stem cell proliferation / lysosome organization / response to dexamethasone / response to testosterone / Association of TriC/CCT with target proteins during biosynthesis / antigen processing and presentation / negative regulation of interleukin-6 production / homeostasis of number of cells / establishment of skin barrier / regulation of macroautophagy / negative regulation of protein-containing complex assembly / negative regulation of MAP kinase activity / cell maturation / : / cholesterol metabolic process / cellular response to starvation / lysosomal lumen / respiratory electron transport chain / determination of adult lifespan / trans-Golgi network / negative regulation of inflammatory response / autophagy / response to estrogen / positive regulation of proteasomal ubiquitin-dependent protein catabolic process / cellular response to tumor necrosis factor / T cell differentiation in thymus / neuron apoptotic process / proteasome-mediated ubiquitin-dependent protein catabolic process / negative regulation of neuron apoptotic process / lysosome / lysosomal membrane / signaling receptor binding / Golgi apparatus / endoplasmic reticulum / extracellular exosome
Similarity search - Function
Glycosyl hydrolase family 30, TIM-barrel domain / Glycosyl hydrolase family 30 TIM-barrel domain / Glycosyl hydrolase family 30, beta sandwich domain / Glycosyl hydrolase family 30 beta sandwich domain / Glycoside hydrolase family 30 / Glycoside hydrolase superfamily
Similarity search - Domain/homology
: / Lysosomal acid glucosylceramidase
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 1.75 Å
AuthorsSchulze, M.-S.
Funding support1items
OrganizationGrant numberCountry
Not funded
CitationJournal: Chemmedchem / Year: 2024
Title: Identification of ss-Glucocerebrosidase Activators for Glucosylceramide hydrolysis.
Authors: Schulze, M.E.D. / Scholz, D. / Jnoff, E. / Hall, A. / Melin, J. / Sands, Z.A. / Rodriguez, E. / Andre, V.M.
History
DepositionMay 17, 2023Deposition site: PDBE / Processing site: PDBE
Revision 1.0Mar 6, 2024Provider: repository / Type: Initial release
Revision 1.1Apr 24, 2024Group: Database references / Category: citation / citation_author
Item: _citation.journal_volume / _citation.page_first ..._citation.journal_volume / _citation.page_first / _citation.page_last / _citation_author.identifier_ORCID
Revision 1.2May 1, 2024Group: Database references / Category: citation / citation_author
Item: _citation.page_first / _citation.page_last / _citation_author.identifier_ORCID
Revision 1.3Nov 6, 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: Glucosylceramidase
B: Glucosylceramidase
hetero molecules


Theoretical massNumber of molelcules
Total (without water)112,5786
Polymers111,2802
Non-polymers1,2984
Water8,179454
1
A: Glucosylceramidase
B: Glucosylceramidase
hetero molecules

A: Glucosylceramidase
B: Glucosylceramidase
hetero molecules


Theoretical massNumber of molelcules
Total (without water)225,15612
Polymers222,5614
Non-polymers2,5958
Water724
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
crystal symmetry operation3_654-x+1,y,-z-1/21
Buried area8580 Å2
ΔGint-18 kcal/mol
Surface area69010 Å2
MethodPISA
Unit cell
Length a, b, c (Å)110.310, 285.640, 91.870
Angle α, β, γ (deg.)90.00, 90.00, 90.00
Int Tables number20
Space group name H-MC2221
Components on special symmetry positions
IDModelComponents
11A-670-

HOH

-
Components

#1: Protein Glucosylceramidase / Acid beta-glucosidase / Alglucerase / Beta-glucocerebrosidase / Beta-GC / D-glucosyl-N- ...Acid beta-glucosidase / Alglucerase / Beta-glucocerebrosidase / Beta-GC / D-glucosyl-N-acylsphingosine glucohydrolase / Imiglucerase


Mass: 55640.168 Da / Num. of mol.: 2
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: GBA, GC, GLUC / Production host: Cricetulus griseus (Chinese hamster)
References: UniProt: P04062, glucosylceramidase, Transferases; Glycosyltransferases; Hexosyltransferases, EC: 3.2.1.104
#2: Polysaccharide 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose


Type: oligosaccharide / Mass: 424.401 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
DescriptorTypeProgram
DGlcpNAcb1-4DGlcpNAcb1-ROHGlycam Condensed SequenceGMML 1.0
WURCS=2.0/1,2,1/[a2122h-1b_1-5_2*NCC/3=O]/1-1/a4-b1WURCSPDB2Glycan 1.1.0
[][D-1-deoxy-GlcpNAc]{[(4+1)][b-D-GlcpNAc]{}}LINUCSPDB-CARE
#3: Sugar ChemComp-NAG / 2-acetamido-2-deoxy-beta-D-glucopyranose / N-acetyl-beta-D-glucosamine / 2-acetamido-2-deoxy-beta-D-glucose / 2-acetamido-2-deoxy-D-glucose / 2-acetamido-2-deoxy-glucose / N-ACETYL-D-GLUCOSAMINE


Type: D-saccharide, beta linking / Mass: 221.208 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C8H15NO6
IdentifierTypeProgram
DGlcpNAcbCONDENSED IUPAC CARBOHYDRATE SYMBOLGMML 1.0
N-acetyl-b-D-glucopyranosamineCOMMON NAMEGMML 1.0
b-D-GlcpNAcIUPAC CARBOHYDRATE SYMBOLPDB-CARE 1.0
GlcNAcSNFG CARBOHYDRATE SYMBOLGMML 1.0
#4: Chemical ChemComp-WSI / 2-[[3-[(4-chlorophenyl)carbamoyl]phenyl]sulfonylamino]benzoic acid


Mass: 430.862 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C20H15ClN2O5S / Feature type: SUBJECT OF INVESTIGATION
#5: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 454 / 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: 3.25 Å3/Da / Density % sol: 62.17 %
Crystal growTemperature: 291 K / Method: vapor diffusion / Details: 2 M (NH4)2SO4, 0.1 M Bis-Tris pH 5.5

-
Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: SOLEIL / Beamline: PROXIMA 1 / Wavelength: 0.97857 Å
DetectorType: DECTRIS PILATUS 6M / Detector: PIXEL / Date: Nov 22, 2016
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.97857 Å / Relative weight: 1
ReflectionResolution: 1.75→47.61 Å / Num. obs: 278631 / % possible obs: 98.79 % / Redundancy: 4.5 % / Rmerge(I) obs: 0.039 / Net I/σ(I): 18.4
Reflection shellResolution: 1.75→1.8 Å / Rmerge(I) obs: 0.538 / Num. unique obs: 10430

-
Processing

Software
NameVersionClassification
PHENIX(1.18.2_3874: ???)refinement
XDSdata reduction
XDSdata scaling
PHASERphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT / Resolution: 1.75→47.61 Å / SU ML: 0.22 / Cross valid method: FREE R-VALUE / σ(F): 1.01 / Phase error: 24.74 / Stereochemistry target values: ML
RfactorNum. reflection% reflection
Rfree0.2137 13955 5.01 %
Rwork0.1903 --
obs0.1915 278631 98.79 %
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT BULK SOLVENT MODEL
Refinement stepCycle: LAST / Resolution: 1.75→47.61 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms7858 0 85 454 8397
Refine LS restraints
Refine-IDTypeDev idealNumber
X-RAY DIFFRACTIONf_bond_d0.018187
X-RAY DIFFRACTIONf_angle_d1.04111166
X-RAY DIFFRACTIONf_dihedral_angle_d16.6382921
X-RAY DIFFRACTIONf_chiral_restr0.0631217
X-RAY DIFFRACTIONf_plane_restr0.0081438
LS refinement shell
Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkRefine-ID% reflection obs (%)
1.75-1.770.38424400.40258339X-RAY DIFFRACTION94
1.77-1.790.37674650.34858766X-RAY DIFFRACTION99
1.79-1.810.32334670.3078814X-RAY DIFFRACTION99
1.81-1.840.31054650.28848881X-RAY DIFFRACTION98
1.84-1.860.31484650.28148751X-RAY DIFFRACTION99
1.86-1.890.26344570.24148778X-RAY DIFFRACTION98
1.89-1.910.26094710.22328910X-RAY DIFFRACTION99
1.91-1.940.26064590.21568783X-RAY DIFFRACTION99
1.94-1.970.23164680.20438777X-RAY DIFFRACTION99
1.97-2.010.24134720.20238864X-RAY DIFFRACTION99
2.01-2.040.24684660.19298901X-RAY DIFFRACTION99
2.04-2.080.244650.19938829X-RAY DIFFRACTION99
2.08-2.120.21914600.19558860X-RAY DIFFRACTION99
2.12-2.160.2494650.1988777X-RAY DIFFRACTION99
2.16-2.210.24624650.19258852X-RAY DIFFRACTION99
2.21-2.260.22714630.18668777X-RAY DIFFRACTION98
2.26-2.310.20934760.18298871X-RAY DIFFRACTION100
2.31-2.380.19524610.18018866X-RAY DIFFRACTION99
2.38-2.450.2234700.18398896X-RAY DIFFRACTION100
2.45-2.530.21774650.19298920X-RAY DIFFRACTION99
2.53-2.620.20234660.19038854X-RAY DIFFRACTION99
2.62-2.720.21474720.18798882X-RAY DIFFRACTION99
2.72-2.840.21234600.19628844X-RAY DIFFRACTION99
2.84-2.990.244700.19948842X-RAY DIFFRACTION99
2.99-3.180.20754680.19678886X-RAY DIFFRACTION99
3.18-3.430.21184700.18498879X-RAY DIFFRACTION99
3.43-3.770.18944660.17768765X-RAY DIFFRACTION99
3.77-4.320.19054650.168825X-RAY DIFFRACTION99
4.32-5.440.16564650.1548881X-RAY DIFFRACTION99
5.44-47.610.20284680.19868806X-RAY DIFFRACTION98

+
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