1OGS

human acid-beta-glucosidase


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.00 Å
  • R-Value Free: 0.230 
  • R-Value Work: 0.195 
  • R-Value Observed: 0.195 

wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 


This is version 2.0 of the entry. See complete history


Literature

X-Ray Structure of Human Acid-Beta-Glucosidase, the Defective Enzyme in Gaucher Disease

Dvir, H.Harel, M.Mccarthy, A.A.Toker, L.Silman, I.Futerman, A.H.Sussman, J.L.

(2003) EMBO Rep 4: 704

  • DOI: https://doi.org/10.1038/sj.embor.embor873
  • Primary Citation of Related Structures:  
    1OGS

  • PubMed Abstract: 

    Gaucher disease, the most common lysosomal storage disease, is caused by mutations in the gene that encodes acid-beta-glucosidase (GlcCerase). Type 1 is characterized by hepatosplenomegaly, and types 2 and 3 by early or chronic onset of severe neurological symptoms. No clear correlation exists between the approximately 200 GlcCerase mutations and disease severity, although homozygosity for the common mutations N370S and L444P is associated with non- neuronopathic and neuronopathic disease, respectively. We report the X-ray structure of GlcCerase at 2.0 A resolution. The catalytic domain consists of a (beta/alpha)(8) TIM barrel, as expected for a member of the glucosidase hydrolase A clan. The distance between the catalytic residues E235 and E340 is consistent with a catalytic mechanism of retention. N370 is located on the longest alpha-helix (helix 7), which has several other mutations of residues that point into the TIM barrel. Helix 7 is at the interface between the TIM barrel and a separate immunoglobulin-like domain on which L444 is located, suggesting an important regulatory or structural role for this non-catalytic domain. The structure provides the possibility of engineering improved GlcCerase for enzyme-replacement therapy, and for designing structure-based drugs aimed at restoring the activity of defective GlcCerase.


  • Organizational Affiliation

    [1] Departments of Structural Biology and Neurobiology, Weizmann Institute of Science, Rehovot 76100, Israel


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Glucosylceramidase
A, B
497Homo sapiensMutation(s): 0 
Gene Names: GBAGCGLUC
EC: 3.2.1.45 (PDB Primary Data), 2.4.1 (PDB Primary Data), 3.2.1.104 (PDB Primary Data)
Membrane Entity: Yes 
UniProt & NIH Common Fund Data Resources
Find proteins for P04062 (Homo sapiens)
Explore P04062 
Go to UniProtKB:  P04062
PHAROS:  P04062
GTEx:  ENSG00000177628 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP04062
Sequence Annotations
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  • Reference Sequence
Oligosaccharides

Help

Entity ID: 2
MoleculeChains Length2D Diagram Glycosylation3D Interactions
2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose
C
2N-Glycosylation
Glycosylation Resources
GlyTouCan:  G42666HT
GlyCosmos:  G42666HT
GlyGen:  G42666HT
Small Molecules
Ligands 2 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
NAG
Query on NAG

Download Ideal Coordinates CCD File 
N [auth A]2-acetamido-2-deoxy-beta-D-glucopyranose
C8 H15 N O6
OVRNDRQMDRJTHS-FMDGEEDCSA-N
SO4
Query on SO4

Download Ideal Coordinates CCD File 
D [auth A]
E [auth A]
F [auth A]
G [auth A]
H [auth A]
D [auth A],
E [auth A],
F [auth A],
G [auth A],
H [auth A],
I [auth A],
J [auth A],
K [auth A],
L [auth A],
M [auth A],
O [auth B],
P [auth B],
Q [auth B],
R [auth B],
S [auth B]
SULFATE ION
O4 S
QAOWNCQODCNURD-UHFFFAOYSA-L
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.00 Å
  • R-Value Free: 0.230 
  • R-Value Work: 0.195 
  • R-Value Observed: 0.195 
  • Space Group: C 2 2 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 107.735α = 90
b = 285.232β = 90
c = 91.678γ = 90
Software Package:
Software NamePurpose
CNSrefinement
DENZOdata reduction
SCALEPACKdata scaling
SHARPphasing

Structure Validation

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Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2003-07-03
    Type: Initial release
  • Version 1.1: 2012-01-25
    Changes: Advisory, Atomic model, Derived calculations, Non-polymer description, Other, Refinement description, Version format compliance
  • Version 1.2: 2019-10-16
    Changes: Data collection, Database references, Derived calculations, Experimental preparation, Other, Source and taxonomy, Structure summary
  • Version 2.0: 2020-07-29
    Type: Remediation
    Reason: Carbohydrate remediation
    Changes: Advisory, Atomic model, Data collection, Derived calculations, Structure summary