2WKL

Velaglucerase alfa


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.70 Å
  • R-Value Free: 0.234 
  • R-Value Work: 0.173 
  • R-Value Observed: 0.176 

wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 


This is version 2.1 of the entry. See complete history


Literature

Characterization of Gene-Activated Human Acid-Beta-Glucosidase: Crystal Structure, Glycan Composition and Internalization Into Macrophages.

Brumshtein, B.Salinas, P.Peterson, B.Chan, V.Silman, I.Sussman, J.L.Savickas, P.J.Robinson, G.S.Futerman, A.H.

(2010) Glycobiology 20: 24

  • DOI: https://doi.org/10.1093/glycob/cwp138
  • Primary Citation of Related Structures:  
    2WKL

  • PubMed Abstract: 

    Gaucher disease, the most common lysosomal storage disease, can be treated with enzyme replacement therapy (ERT), in which defective acid-beta-glucosidase (GlcCerase) is supplemented by a recombinant, active enzyme. The X-ray structures of recombinant GlcCerase produced in Chinese hamster ovary cells (imiglucerase, Cerezyme) and in transgenic carrot cells (prGCD) have been previously solved. We now describe the structure and characteristics of a novel form of GlcCerase under investigation for the treatment of Gaucher disease, Gene-Activated human GlcCerase (velaglucerase alfa). In contrast to imiglucerase and prGCD, velaglucerase alfa contains the native human enzyme sequence. All three GlcCerases consist of three domains, with the active site located in domain III. The distances between the carboxylic oxygens of the catalytic residues, E340 and E235, are consistent with distances proposed for acid-base hydrolysis. Kinetic parameters (K(m) and V(max)) of velaglucerase alfa and imiglucerase, as well as their specific activities, are similar. However, analysis of glycosylation patterns shows that velaglucerase alfa displays distinctly different structures from imiglucerase and prGCD. The predominant glycan on velaglucerase alfa is a high-mannose type, with nine mannose units, while imiglucerase contains a chitobiose tri-mannosyl core glycan with fucosylation. These differences in glycosylation affect cellular internalization; the rate of velaglucerase alfa internalization into human macrophages is at least 2-fold greater than that of imiglucerase.


  • Organizational Affiliation

    Department of 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 
EC: 3.2.1.45
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, D
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 
E [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 
F [auth A]
G [auth A]
H [auth A]
I [auth A]
J [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],
N [auth A],
O [auth B],
P [auth B],
Q [auth B],
R [auth B],
S [auth B],
T [auth B],
U [auth B],
V [auth B],
W [auth B]
SULFATE ION
O4 S
QAOWNCQODCNURD-UHFFFAOYSA-L
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.70 Å
  • R-Value Free: 0.234 
  • R-Value Work: 0.173 
  • R-Value Observed: 0.176 
  • Space Group: C 2 2 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 109.371α = 90
b = 285.552β = 90
c = 91.693γ = 90
Software Package:
Software NamePurpose
REFMACrefinement
HKL-2000data reduction
SCALEPACKdata scaling
PHASERphasing

Structure Validation

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Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2009-09-22
    Type: Initial release
  • Version 1.1: 2011-05-08
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Version format compliance
  • Version 2.0: 2020-07-29
    Type: Remediation
    Reason: Carbohydrate remediation
    Changes: Atomic model, Data collection, Derived calculations, Other, Structure summary
  • Version 2.1: 2023-12-13
    Changes: Data collection, Database references, Refinement description, Structure summary