[English] 日本語
Yorodumi
- PDB-6q1p: Glucocerebrosidase in complex with pharmacological chaperone norIMX8 -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 6q1p
TitleGlucocerebrosidase in complex with pharmacological chaperone norIMX8
ComponentsGlucosylceramidase
KeywordsHYDROLASE/INHIBITOR / pharmacological chaperone / Gaucher disease / glycosidase / inhibitor / pKa / HYDROLASE / HYDROLASE-INHIBITOR complex
Function / homology
Function and homology information


positive regulation of protein lipidation / steryl-beta-glucosidase activity / beta-glucoside catabolic process / positive regulation of neuronal action potential / cerebellar Purkinje cell layer formation / galactosylceramidase / termination of signal transduction / galactosylceramidase activity / positive regulation of autophagy of mitochondrion in response to mitochondrial depolarization / lymphocyte migration ...positive regulation of protein lipidation / steryl-beta-glucosidase activity / beta-glucoside catabolic process / positive regulation of neuronal action potential / cerebellar Purkinje cell layer formation / galactosylceramidase / termination of signal transduction / galactosylceramidase activity / positive regulation of autophagy of mitochondrion in response to mitochondrial depolarization / lymphocyte migration / glucosylceramidase / glucosylceramide catabolic process / scavenger receptor binding / regulation of lysosomal protein catabolic process / sphingosine biosynthetic process / autophagosome organization / glucosylceramidase activity / microglial cell proliferation / regulation of TOR signaling / glucosyltransferase activity / ceramide biosynthetic process / lipid storage / sphingolipid metabolic process / response to thyroid hormone / microglia differentiation / Glycosphingolipid catabolism / pyramidal neuron differentiation / lipid glycosylation / brain morphogenesis / response to pH / Hydrolases; Glycosylases; Glycosidases, i.e. enzymes that hydrolyse O- and S-glycosyl compounds / positive regulation of protein-containing complex disassembly / motor behavior / neuromuscular process / Transferases; Glycosyltransferases; Hexosyltransferases / hematopoietic stem cell proliferation / lysosome organization / response to testosterone / response to dexamethasone / glycosyltransferase activity / Association of TriC/CCT with target proteins during biosynthesis / negative regulation of interleukin-6 production / homeostasis of number of cells / antigen processing and presentation / regulation of macroautophagy / establishment of skin barrier / negative regulation of protein-containing complex assembly / positive regulation of protein dephosphorylation / cell maturation / cholesterol metabolic process / respiratory electron transport chain / cellular response to starvation / lysosomal lumen / negative regulation of MAP kinase activity / 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 / T cell differentiation in thymus / cellular response to tumor necrosis factor / proteasome-mediated ubiquitin-dependent protein catabolic process / neuron apoptotic 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
Chem-P8Y / Glucosylceramidase / Lysosomal acid glucosylceramidase
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / MOLECULAR REPLACEMENT / Resolution: 2.796 Å
AuthorsVickers, C. / Withers, S.G. / Boraston, A.B.
Funding support Canada, 1items
OrganizationGrant numberCountry
Canadian Institutes of Health Research (CIHR) Canada
CitationJournal: To Be Published
Title: Pharmacological chaperones for GCase that switch conformation with pH enhance enzyme levels in Gaucher animal models.
Authors: Santana, A.G. / Robinson, K. / Vickers, C. / Chen, H. / Zhou, S. / Boraston, A.B. / Clarke, L.A. / Withers, S.G.
History
DepositionAug 5, 2019Deposition site: RCSB / Processing site: RCSB
Revision 1.0Aug 19, 2020Provider: repository / Type: Initial release

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Glucosylceramidase
B: Glucosylceramidase
hetero molecules


Theoretical massNumber of molelcules
Total (without water)116,06041
Polymers111,2802
Non-polymers4,77939
Water2,612145
1
A: Glucosylceramidase
hetero molecules


Theoretical massNumber of molelcules
Total (without water)57,86219
Polymers55,6401
Non-polymers2,22218
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
2
B: Glucosylceramidase
hetero molecules


Theoretical massNumber of molelcules
Total (without water)58,19722
Polymers55,6401
Non-polymers2,55721
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
3
A: Glucosylceramidase
B: Glucosylceramidase
hetero molecules

A: Glucosylceramidase
B: Glucosylceramidase
hetero molecules


Theoretical massNumber of molelcules
Total (without water)232,12082
Polymers222,5614
Non-polymers9,55978
Water724
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
crystal symmetry operation3_454-x-1,y,-z-1/21
Buried area18760 Å2
ΔGint-278 kcal/mol
Surface area72080 Å2
MethodPISA
Unit cell
Length a, b, c (Å)110.709, 284.709, 91.767
Angle α, β, γ (deg.)90.000, 90.000, 90.000
Int Tables number20
Space group name H-MC2221

-
Components

-
Protein , 1 types, 2 molecules AB

#1: Protein Glucosylceramidase / / Glucocerebrosidase


Mass: 55640.168 Da / Num. of mol.: 2
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Production host: Cricetulus griseus (Chinese hamster)
References: UniProt: B2R6A7, UniProt: P04062*PLUS, glucosylceramidase

-
Sugars , 3 types, 5 molecules

#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.: 2
Source method: isolated from a genetically manipulated source
DescriptorTypeProgram
DGlcpNAcb1-4DGlcpNAcb1-Glycam 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
[]{[(4+1)][b-D-GlcpNAc]{[(4+1)][b-D-GlcpNAc]{}}}LINUCSPDB-CARE
#3: Polysaccharide alpha-L-fucopyranose-(1-6)-2-acetamido-2-deoxy-beta-D-glucopyranose


Type: oligosaccharide / Mass: 367.349 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
DescriptorTypeProgram
LFucpa1-6DGlcpNAcb1-Glycam Condensed SequenceGMML 1.0
WURCS=2.0/2,2,1/[a2122h-1b_1-5_2*NCC/3=O][a1221m-1a_1-5]/1-2/a6-b1WURCSPDB2Glycan 1.1.0
[]{[(4+1)][b-D-GlcpNAc]{[(6+1)][a-L-Fucp]{}}}LINUCSPDB-CARE
#7: 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 / N-Acetylglucosamine


Type: D-saccharide, beta linking / Mass: 221.208 Da / Num. of mol.: 2
Source method: isolated from a genetically manipulated source
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

-
Non-polymers , 4 types, 179 molecules

#4: Chemical
ChemComp-EDO / 1,2-ETHANEDIOL / ETHYLENE GLYCOL / Ethylene glycol


Mass: 62.068 Da / Num. of mol.: 16 / Source method: obtained synthetically / Formula: C2H6O2
#5: Chemical
ChemComp-SO4 / SULFATE ION / Sulfate


Mass: 96.063 Da / Num. of mol.: 16 / Source method: obtained synthetically / Formula: SO4
#6: Chemical ChemComp-P8Y / (2S,3S,4S,5R)-2-{[(4-methylpentyl)sulfonyl]methyl}piperidine-3,4,5-triol


Mass: 295.396 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C12H25NO5S / Feature type: SUBJECT OF INVESTIGATION
#8: Water ChemComp-HOH / water / Water


Mass: 18.015 Da / Num. of mol.: 145 / 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: 3.27 Å3/Da / Density % sol: 62.42 %
Crystal growTemperature: 291.15 K / Method: vapor diffusion, hanging drop
Details: 1.5 M (NH4)2SO4, 0.1 M Bis Tris (pH 4.9) containing 0.1 M CsCl

-
Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: ROTATING ANODE / Type: RIGAKU MICROMAX-007 HF / Wavelength: 1.54178 Å
DetectorType: DECTRIS PILATUS3 R 200K-A / Detector: PIXEL / Date: Jan 16, 2017
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1.54178 Å / Relative weight: 1
ReflectionResolution: 2.796→50 Å / Num. obs: 36172 / % possible obs: 99.9 % / Redundancy: 5.7 % / Biso Wilson estimate: 48.89 Å2 / Rmerge(I) obs: 0.161 / Rpim(I) all: 0.072 / Rrim(I) all: 0.176 / Χ2: 0.9 / Net I/σ(I): 4.5
Reflection shell

Diffraction-ID: 1

Resolution (Å)Redundancy (%)Rmerge(I) obsNum. unique obsCC1/2Rpim(I) allRrim(I) allΧ2% possible all
2.8-2.8540.55217720.8250.3150.6380.62100
2.85-2.94.20.50517580.8650.2820.580.617100
2.9-2.964.40.45818120.8720.2480.5230.624100
2.96-3.024.50.3917770.9090.2060.4430.606100
3.02-3.084.70.33618050.9180.1730.3790.641100
3.08-3.1550.2917770.9390.1440.3240.621100
3.15-3.235.20.24317770.9550.1170.270.66100
3.23-3.325.60.2118130.9650.0970.2310.66100
3.32-3.426.10.19518030.9790.0850.2130.738100
3.42-3.536.70.18917800.9840.0790.2050.798100
3.53-3.656.80.16518010.9820.0680.1791.165100
3.65-3.86.70.17818010.9750.0740.1921.646100
3.8-3.976.60.15318030.9890.0640.1660.928100
3.97-4.186.60.15717990.9890.0660.1711.026100
4.18-4.446.40.12918080.9830.0550.1411.639100
4.44-4.796.50.11818340.9940.050.1281.136100
4.79-5.276.60.09218210.9940.0390.10.701100
5.27-6.036.40.11118300.990.0470.120.725100
6.03-7.596.20.11718660.9870.0510.1280.792100
7.59-505.50.06219350.9950.0290.0690.8798.7

-
Processing

Software
NameVersionClassification
HKL-2000data scaling
PHENIX1.13_2998refinement
PDB_EXTRACT3.25data extraction
HKL-2000data reduction
PHASERphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT / Resolution: 2.796→33.993 Å / SU ML: 0.36 / Cross valid method: THROUGHOUT / σ(F): 1.33 / Phase error: 26.25
RfactorNum. reflection% reflection
Rfree0.2404 1833 5.16 %
Rwork0.1988 --
obs0.201 35557 97.91 %
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å
Displacement parametersBiso max: 128.66 Å2 / Biso mean: 43.8092 Å2 / Biso min: 17.18 Å2
Refinement stepCycle: final / Resolution: 2.796→33.993 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms7739 0 290 145 8174
Biso mean--65.11 39.93 -
Num. residues----986
LS refinement shell

Refine-ID: X-RAY DIFFRACTION / Rfactor Rfree error: 0

Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection Rwork% reflection obs (%)
2.7963-2.87190.33831330.2717220584
2.8719-2.95640.35131410.2714251897
2.9564-3.05170.29311350.2543259699
3.0517-3.16070.2841330.24382624100
3.1607-3.28720.28851380.2142629100
3.2872-3.43660.25991410.20512611100
3.4366-3.61760.23071430.19472615100
3.6176-3.8440.22811540.18612627100
3.844-4.14030.24561640.1868253396
4.1403-4.55610.20971350.1714262299
4.5561-5.21340.17911250.1649263198
5.2134-6.56050.22171460.19992702100
6.5605-33.9930.22391450.1952811100

+
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